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"Kanker payudara adalah jenis kanker yang memiliki kasus baru terbanyak dan penyebab kematian tertinggi di kalangan wanita. Hal tersebut menjadikan pemahaman mengenai konsep pengobatan presisi (precision medicine) perlu dikembangkan, salah satunya dengan penggunaan kultur primer dari jaringan kanker pasien. Epidermal growth factor receptor (EGFR) telah dilaporkan umum digunakan sebagai marker prognostik kanker payudara melalui deteksi protein menggunakan metode immunohistokimia (IHK). Namun, metode tersebut memiliki kekurangan dalam menjadi acuan penentuan terapi adjuvant. Penggunaan kultur primer sebagai pengganti cell lines dalam penelitian kanker perlu terus dikembangkan karena lebih mewakili karakteristik fenotipe dan genotipe dari jaringan kanker in vivo. Oleh sebab itu, penelitian ini bertujuan untuk mengetahui tingkat ekspresi relatif gen EGFR pada sampel kultur primer dan jaringan asalnya serta mengetahui perbandingan ekspresi relatif gen EGFR pada sampel jaringan jinak dan jaringan ganas kanker payudara. Metode yang digunakan, yaitu melalui deteksi mRNA gen EGFR dengan semi kuantitatif RT-PCR pada dua pasien yang mewakili jaringan jinak dan ganas. Hasil penelitian menunjukkan tidak terdapat perbedaan signifikan antara ekspresi EGFR pada kultur primer dan jaringan asal, serta ekspresi EGFR pada jaringan ganas lebih tinggi dibandingkan dengan jaringan jinak. Berdasarkan hasil yang diperoleh, dapat disimpulkan bahwa kultur primer dapat dijadikan model alternatif dalam penelitian kanker, serta EGFR dapat dijadikan marker potensial dalam menentukan tingkat agresivitas kanker payudara.

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Breast cancer is a type of cancer that has a highest rate of incidence as well as mortality among women. This makes the understanding of the concept of precision medicine need to be continuously developed, in wich one of the methods is through using primary cultures from patient's tissue. It has been reported that epidermal growth factor receptor (EGFR) is commonly used as a prognostic marker of breast cancer through protein detection using the Immunohistochemical (IHC) method. However, this method has shortcomings in being a reference for determining adjuvant therapy. The use of primary culture as a subtitute cell lines in cancer research needs to be developed due to its more representative of the phenotype and genotype characteristics of cancer tissue in vivo. Therefore, this study aims to determine the relative expression level of the EGFR gene in primary culture sample and its tissue origin as well as comparing the relative expression of the EGFR gene in samples of benign tissue and malignant tissue of breast cancer. The method used is the detection of EGFR gene mRNA with semi-quantitative RT-PCR in two patients representing benign and malignant tissues. The results showed that there was no significant difference between EGFR expression in primary culture and tissue of origin, and EGFR expression in malignant tissue was higher than in benign tissue. Hence, it can be concluded that primary culture can be used as an alternative model in cancer research, and EGFR can be used as a potential marker in determining aggressiveness level of breast cancer."

"Latar Belakang. Epidermal Growth Factor Receptor mengatur beberapa proses selular penting. Overekspresi EGFR merupakan penanda negatif prognosis pada glioma. Metode. Tujuh belas pasien astrositoma dilakukan pemeriksaan imunohistokimia untuk mengevaluasi overekspresi EGFR. Seluruh pasien dievaluasi Karnofsky Performance Score 1 tahun pasca operasi. Hasil. Sembilan pasien high-grade glioma, 67 memiliki overekspresi EGFR yang positif dan hanya 1 pasien yang hidup dengan KPS 70. Empat pasien low-grade glioma dengan overekspresi EGFR yang positif, memiliki KPS 0. Kesimpulan. Low-grade glioma dengan overekspresi EGFR yang positif memiliki KPS yang rendah pada 1 tahun pasca operasi.

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Background. Epidermal Growth Factor Receptor regulate several important cellular process. EGFR overexpression is one of negative prognostic marker in glioma.

Method. Seventeen patients with astrocytoma were performed immunohistochemistry to evaluate EGFR overexpression. All of this patient evaluate for Karnofsky Performance Score at 1 year after surgery.

Hasil. Nine patients with high grade glioma, 67 have positive EGFR overexpression, and only 1 patient still alive with KPS 70. Four patient in low grade glioma with positive EGFR overexpression have KPS 0.

Conclusion. Low grade glioma with positive EGFR overexpression have a poor KPS at 1 year after surgery."

"Pendahuluan: Tyrosine Kinase Inhibitors (TKIs) sangat efektif terhadap KankerParu jenis Karsinoma Bukan Sel Kecil (KPKBSK) dengan mutasi EpidermalGrowth Factor Receptor (EGFR). Gefitinib dan Erlotinib adalah generasi pertamaEGFR-TKI untuk pengobatan KPKBSK dengan mutasi EGFR. Obat-obat ini telahtersedia melalui asuransi kesehatan di Indonesia untuk pasien Adenokarsinomaparu dengan mutasi EGFR. Data mengenai efikasi dan toksisitas EGFR-TKI saatini belum tersedia di Indonesia.Metode: Kami melakukan analisis observasional kohort retrospektif pada pasienAdenokarsinoma paru dengan mutasi EGFR di RSUP Persahabatan, JakartaIndonesia dari Januari 2015 sampai dengan Desember 2017. Kami meninjaurekam medis 331 pasien dengan diagnosis Adenokarsinoma paru dengan mutasiEGFR stage lanjut yang diobati dengan EGFR-TKI generasi pertama. Sebanyak192 subjek yang memenuhi kriteria inklusi.Hasil: Subjek yang mendapatkan Gefitinib (n=132) dan Erlotinib (n=60). Medianprogression free survival (PFS) sebanding antara Gefitinib dan Erlotinib (9,0 dan7,0 bulan, interval kepercayaan 95% [IK] 0,57-1,07, p=0,126). Median Overallsurvival (OS) dan angka tahan hidup 1 tahun masing-masing kelompok adalah44,5 vs 39,5 bulan (95% IK 0,35-1,29, p=0,670) dan 92% berbanding 92%(p=0,228). Terdapat toksisitas termasuk diare, paronikia, skin rash dan stomatitisyang diamati tetapi tidak ada perbedaan yang bermakna pada toksisitas derajat 3atau 4 antara kedua kelompok (p=0,713).Kesimpulan: Kedua EGFR-TKIs generasi pertama sebanding dalam PFS dan OS,meskipun Gefitinib terlihat lebih tinggi, tetapi secara statistik tidak bermakna dankeduanya memiliki toksisitas yang sebanding dan dapat ditoleransi.

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Introductions: Tyrosine kinase inhibitors (TKIs) are effective against non-smallcell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR)mutation. Gefitinib and erlotinib are the first-generation EGFR-TKIsrecommended as first-line treatments for NSCLC with EGFR mutations and areavailable through Universal Health Coverage in Indonesia for lungadenocarcinoma patients with EGFR mutations. However, the efficacy and safetydata of EGFR-TKIs are unavailable in Indonesia.Methods: We did a retrospective cohort analysis of the patients of lungadenocarcinoma with EGFR mutations treated in Persahabatan Hospital Jakarta,Indonesia, between January 2015 and December 2017. We reviewed the recordsof 331 patients with advanced stage lung adenocarcinoma with EGFR mutationtreated with the first-generation EGFR-TKIs. The subjects were 192 patients whomet the inclusion criteria.Results: Subjects were receiving gefitinib (n=132) and erlotinib (n=60). Medianprogression-free survival (PFS) was comparable between gefitinib and erlotinib(9.0 vs 7.0 months, 95% confidence interval [CI] 0.57-1.07, p=0.126). Themedian overall survival (OS) and 1-year survival were 44.5 vs 39.5 months(95%CI 0.35-1.29, p=0.228; and 92% vs 92%, p=0.228, respectively). Reportedtoxicities were diarrhea, paronychia, rash, and stomatitis but not of significantdifference between grade 3 or 4 toxicities (p=0.713).Conclusions: The PFS and OS of the first-generation EGFR-TKIs werecomparable, although gefitinib PFS and OS was shown to be better, but withoutsignificance. Both gefitinib and erlotinib had comparable and tolerable adverseeffects"

"Latar Belakang: Kanker paru merupakan kanker terbanyak kedua yang terdiagnosis dan menjadi penyebab terbanyak kematian akibat kanker. Pemberian afatinb sebagai terapi target Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibitor (TKI saat ini telah menjadi terapi standar untuk pasien adenokarsinoma paru dengan mutasi EGFR di Indonesia, termasuk di RSUP Persahabatan. Penelitian ini dilakukan untuk menganalisis pemberian terapi afatinib pada pasien adenokarsinoma paru dengan mutasi EGFR di RSUP Persahabatan.Metode: Desain penelitian ini adalah kohort retrospektif menggunakan data rekam medis fisik dan elektronik, dilakukan di Poli Onkologi RSUP Persahabatan, dengan teknik total sampling. Subjek penelitian adalah pasien adenokarsinoma paru dengan mutasi EGFR yang mendapatkan afatinib pada Januari 2018-Desember 2021 di Poli Onkologi RSUP Persahabatan yang memenuhi kriteria penelitian.Hasil: Didapatkan 116 subjek penelitian, pasien adenokarsinoma paru dengan mutasi EGFR yang mendapatkan afatinib di RSUP Persahabatan dengan karakteristik lebih banyak laki-laki (52,6%), kelompok usia <65 tahun (80,2%), suku Jawa (81,9%), tanpa faktor risiko keganasan di keluarga (82,8%). Saat terdiagnosis subjek penelitian lebih banyak dengan stage IVA (75%), metastasis pleura (59,5%), mutasi EGFR delesi ekson 19 (53,4%) status tampilan 0-1 (75,9%) dan metastasis otak didapatkan pada 19% subjek. Nilai median progression free survivival (PFS) subjek penelitian yang mendapat afatinib adalah 13 bulan (95%IK 10,5-15,5 bulan), dan nilai median overall survival (OS) adalah 17 bulan (95%IK 14,9-19,1 bulan). Angka tahan hidup satu tahun yang didapat 65,1% dan Objective Respons Rate (ORR) adalah 36,1%. Sebanyak 35,3% subjek mendapatkan penurunan dosis afatinib 20 mg atau 30 mg. Toksisitas nonhematologi tersering pada pada penelitian ini adalah diare (74,1%), diikuti oleh stomatitis (61,2%), ruam kulit (59,5%) dan paronikia (49,1%).Kesimpulan: Afatinib sebagai terapi lini pertama memberikan luaran yang cukup baik untuk pasien adenokarsinoma paru dengan mutasi EGFR di RSUP Persahabatan dengan efek samping samping nonhematologi yang dapat dikelola. Riwayat penurunan dosis afatinib tidak memengaruhi angka kesintasan.

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Background: Lung cancer is the second most diagnosed cancer and the most common cause of death from cancer. Afatinib as targeted therapy with Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibitor (TKI) has now become standard therapy for lung adenocarcinoma patients with EGFR mutations in Indonesia, including at RSUP Persahabatan. This study was conducted to analyze the administration of afatinib therapy in lung adenocarcinoma patients with EGFR mutations at Persahabatan General Hospital.

Metode: Design of the study was retrospective cohort using secondary data, physical and electronic medical records at Oncology Clinic Persahabatan Hospital with total sampling technique. Subject of this study were medical records of lung adenocarcinoma patients with EGFR mutation and received afatinib therapy by January 2018- December 2021 which met the inclusion criteria.

Results: There were 116 subjects of lung adenocarcinoma with EGFR mutation and received afatinib at Persahabatan Hospital, with predominant of male (52,6%), age <65 years old (80,2%), Javanese (81,9%), without history of cancer in family (82,8%). Most of subjects are diagnosed as lung adenocarcinoma at stage IVA (75%), with most of them have pleural metastases (59,5%), EGFR mutation with exon 19 deletion (53,4%), performa status 0-1 (75,9%), and brain metastases were found in 19% of subject. The median progression free survival (PFS) of subjects was 13 months (95% CI 10.5-15.5 months), and the median overall survival (OS)was 17 months (95% CI 14.9- 19.1 months). The one-year survival rate was 65.1% and the Objective Response Rate (ORR) was 36,1%. As many as 35.3% of subjects had adjustment dose of afatinib to 20 mg or 30 mg The most common non-hematological toxicity found was diarrhea (74.1%), followed by stomatitis (61.2%), skin rash (59.5%) and paronychia (49.1%).

Conclusion: Afatinib as a first-line therapy provides a good outcome for lung adenocarcinoma patients with EGFR mutations at Persahabatan General Hospital with manageable non-hematological adverse events. History of adjustment dose of afatinib did not affect survival rate."

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Latar belakang: Kista dan tumor odontogenik adalah lesi yang terjadi pada rahang dan berasal dari sisa epitel pembentuk gigi. EGFR adalah salah satu reseptor growth factor yang penting sebagai regulator proliferasi dan diferensiasi sel, diantaranya perkembangan dan morfogenesis gigi. EGFR juga dikenal  sebagai proto onkogen yang menginisiasi signalling pathway pada terjadinya beberapa tumor ganas. Penelitian melaporkan adanya peningkatan ekspresi EGFR pada beberapa kista dan tumor odontogenik sebagaimana yang terjadi pada tumor ganas. Tujuan: Untuk melihat dan membuat suatu profil ekspresi EGFR pada kista dan tumor odontogenik. Metode penelitian: 73 blok parafin kista dan tumor odontogenik didapatkan secara consecutive sampling dari data spesimen pada Departemen Patologi Anatomi FKUI/RSUPN-CM selama periode November 2015 – November 2019. Seluruh sampel diperiksa secara imunohistokimia menggunakan antibodi EGFR.  Hasil: Didapatkan 7 jenis lesi odontogenik: kista radikular (4), kista dentigerous (5), OKC (5), ameloblastoma (54), AOT (1), CEOT (2), ameloblastic carcinoma (2). Seluruh sampel memberikan ekspresi EGFR yang positif, dengan lokasi ekspresi pada sitoplasma. Skor EGFR bervariasi antara 1-2 dengan rerata 1,34. Intensitas beragam terdiri dari 41 % sampel lemah, 48% sampel sedang dan 11% sampel kuat.  Kesimpulan: EGFR berperan dalam terjadinya kista dan tumor odontogenik. Lokasi pulasan yang dominan terjadi pada sitoplasma sesuai dengan karakteristik kista dan tumor odontogenik yang tumbuh dan berkembang lambat.

 

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Background: Odontogenic cysts and tumors are lesions that occur in the jaw and derived from the remnants of tooth-forming epithelium. EGFR is one of  the growth factor receptors that is important as a regulator of cells proliferation and differentiation, including the development and morphogenesis of the tooth.  EGFR is also known as a protooncogen which initiates signalling pathway in the occurrence of several malignant tumors. Recent studies have reports an increase EGFR expression on odontogenic cysts and tumors as occurs in malignant tumors. Objective: This study aims to observe and make an expression profile of odontogenic cysts and tumors. Method: 73 paraffin blocks were collected through consecutive sampling from speciment data in Pathological Anatomy Department FKUI/RSUPN-CM during 2015 – 2019 period. The EGFR expression were detected using immunohistochemistry. Results: There were 7 types of odontogenic lesion: radicular cyst (4), dentigerous cyst (5), OKC (5), ameloblastoma (54), AOT (1), CEOT (2), ameloblastic carcinoma (2). All samples showed positive expression of EGFR and staining location on cytoplasm. EGFR score was vary between 1 – 2 with a mean of 1,34. Intensity of staining were consisted of 41% samples have weak staining, 48% samples have moderate staining and 11% sampels have strong staining Conclusion: EGFR have a role in the occurance of odontogenic cysts and tumors. All the staining location occurs in the cytoplasm was appropriate to the characteristics of these lessions that grows and develops slowly.

 

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"Latar Belakang : Mutasi pada gen Epidermal Growth Factor Receptor (EGFR) berhubungan dengan karsinogenesis Adenokarsinoma paru terutama pada usia muda yang tidak terpajan cukup lama oleh rokok sebagai karsinogen. Penelitian ini untuk mengetahui profil mutasi gen EGFR dan angka tahan hidup pasien adenokarsinoma paru usia muda. Metode: Penelitian observasional kohort retrospektif dan prospektif pada Adenokarsinoma paru usia muda yakni usia <45 tahun dibandingkan dengan usia yang lebih tua. Data diambil dari catatan medis rumah sakit umum pusat Persahabatan Jakarta 2012-2013 dan dilakukan observasi progresivitas dan kematian selama 2 tahun pasca tegak diagnosis. Hasil: Total pasien Adenokarsinoma paru adalah 218 orang terdiri dari 65 orang usia muda dan 153 orang usia tua. Karakteristik Adenokasrsinoma paru usia muda adalah perempuan (58,3%), bukan perokok (66,7%), stage lanjut (98,5%), status tampilan WHO ≤2, metastasis ke luar rongga toraks (43,1%). Proporsi mutasi EGFR positif pada usia muda lebih tinggi dibandingkan usia tua (70,8%vs51%; p=0,007). Mutasi gen EGFR usia muda terdiri dari 36,9% delesi ekson 19; 30,8% mutasi ekson 21 L858R; 3,1% mutasi ekson 21 L861Q dan 29,2% wild type. Masa tengah tahan hidup Adenokarsinoma paru usia muda dengan EGFR positif yang diberikan EGFR tyrosine kinase inhibitor adalah 652 hari (590-713 hari, IK 95%) dengan angka tahan hidup 1 tahun adalah 87,5% dan masa bebas penyakit adalah 345 hari (IK 95%, 323-366 hari). Delesi ekson 19 memberikan masa bebas penyakit yang lebih baik dibandingkan dengan mutasi ekson 21 (RR 2,361; IK 95% 1,126-4,952; p=0,023). Masa tengah tahan hidup Adenokarsinoma paru usia muda dengan mutasi EGFR wild type yang mendapat kemo/kemoradioterapi adalah 515 hari (IK 95%, 487-542) dengan angka tahan hidup 1 tahun adalah 70,7% dan masa bebas penyakit adalah 202 hari (IK 95%, 137-266 hari). Kesimpulan: Profil mutasi gen EGFR pada Adenokarsinoma paru usia muda sangat penting dalam pemilihan terapi lini pertama sehingga dapat meningkatkan angka tahan hidup.

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Introduction: Epidermal Growth Factor Receptor (EGFR) mutation is associated with Lung Adebocarcinoma carcinogenesis particularly in young patients which don?t have long exposure to smoke as carcinogen. This study investigate Profile of Epidermal Growth Factor Receptor Mutation and Survival in Young Patients with lung Adenocarcinoma.

Method: Retrospective and prospective observational cohort study in lung Adenocarcinoma <45 years old compare with olders. Data are taken from medical record Persahabatan hospital Jakarta 2012-2013 and we observed for progressivity and mortality in 2 years since diagnosis.

Results: A total 218 lung Adenocarcinoma consists of 65 young patients and 153 olders. Young lung Adenocarcinomas are female (58,3%), nonsmokers (66,7%), advanced stage (98,5%), performance status WHO ≤2, extrathoracic metastatics (43,1%). EGFR mutation in youngers are higher than olders (70,8%vs51%; p=0,007). Mutation in young patients consists are 36,9% exon 19 deletion; 30,8% exon 21 L858R mutation; 3,1% exon 21 L861Q mutation and 29,2% wild type. Overall survival (OS) young patients with EGFR mutation positive treated with EGFR tyrosine kinase inhibitor are 652 days (95% CI, 590-713 days), 1 year survival is 87,5% and progression free survival (PFS) are 345 days (95% CI, 323-366 days). Exon 19 deletion give higher PFS than exon 21 (RR 2,361; IK 95% 1,126-4,952; p=0,023). Overall survival young patients with EGFR wild type treated with conventional chemotherapy are 515 days (487-542 days, 95%), 1 year survival is 70,7% and their PFS are 202 days (137-266 days, 95% CI).

Conclusion: EGFR mutation profile in young lung Adenocarcinoma is important to choose first line therapy so that can increase their survival."

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Epidermal growth factor receptor variant III (EGFRvIII) telah ditemukan sebagai protein reseptor spesifik pada beberapa jenis sel kanker. Protein tersebut merupakan hasil ekspresi dari salah satu jenis mutan gen EGFR, yaitu gen EGFRvIII. Mutasi pada gen EGFRvIII terjadi karena adanya delesi ekson  2  hingga 7 yang merupakan bagian dari domain ekstraselular yang berinteraksi dengan ligan alaminya. Keberadaan EGFRvIII yang spesifik hanya pada sel kanker memberikan potensi bagi protein tersebut untuk dijadikan sebagai molekul target pada terapi penargetan kanker dengan antibodi monoklonal. Fragmen antibodi untai tunggal (ScFv) anti-EGFRvIII merupakan antibodi monoklonal yang dapat digunakan sebagai ligan spesifik terhadap EGFRvIII dalam simulasi terapi penargetan kanker. Antibodi ScFv-anti-EGFRvIII dapat diproduksi menggunakan plasmid pPICZα-ScFv-anti-EGFRvIII-egfp. Plasmid rekombinan ini memiliki promotor indusibel AOX1 dan sinyal sekresi matting factor-a yang dapat ditransformasikan pada Komagataella phaffii sehingga antibodi ScFv-anti-EGFRvIII dapat disekresikan oleh sel inang. Tujuan penelitian ini adalah mendapatkan klona K. phaffii transforman yang membawa gen ScFv-anti-EGFRvIII. Plasmid diisolasi dari Escherichia coli TOP10F` dan dipurifikasi dengan pelarut organik. Plasmid kemudian dipotong dengan enzim SacI sehingga diperoleh plasmid linear yang berukuran 5.150 bp. Metode transformasi yang digunakan adalah elektroporasi. Seleksi K. phaffii transforman dilakukan pada medium seleksi yang mengandung antibiotik zeocin. Hasil penelitian menunjukkan klona K. phaffii transforman yang mengandung plasmid rekombinan  pPICZα-ScFv-anti-EGFRvIII-egfp (5150 bp) berhasil diperoleh. Hasil seleksi K. phaffii transforman dengan replica platting menunjukkan, bahwa seluruh koloni tunggal transforman yang terpilih dapat tumbuh dengan baik pada konsentrasi zeocin 100 μg/mL. Hal tersebut mengindikasikan, bahwa plasmid rekombinan pPICZα-ScFv-anti-EGFRvIII-egfp dapat berintegrasi ke dalam genom K. phaffii secara stabil.

 

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Cancer is a disease caused by abnormal proliferation of cell which can produce fatal effects for an organ system. Epidermal growth factor receptor variant III (EGFRvIII) has been found to be a spesific receptor protein in several tyoes of cancer cells. The protein is expressed by one of many types of mutant from EGFR gene, namely EGFRvIII. Mutation in EGFRvIII gene occur because of deletion on exon 2 to exon 7 that are part of the extracellular domain that interacts with their natural ligand. The specificity of EGFRvIII on cancer cells EGFRvIII provides a potential for the protein to be used as target molecule in cancer-targeting therapy with monoclonal antibodies. Single-chain variable fragment (ScFv) of anti-EGFRvIII is a monoclonal antibody that can be used as specific ligands against EGFRvIII in simulating cancer-targeting theraphy. The ScFv-anti-EGFRvIII antibody can be produced using the pPICZα-ScFv-anti-EGFRvIII-egfp plasmid. This recombinant plasmid has an inducible AOX1 promoter and matting factor-a secretion signal that can be transformed into Komagataella phaffii so that the ScFv-anti-EGFRvIII antibody can be expressed extracellularly. The purpose of this study is to obtain a K. phaffii transformant clone that carries the ScFv-anti-EGFRvIII gene. The plasmid were isolated from Escherichia coli TOP10F` and purified. Plasmid were then cut with the SacI enzym so that a 5.150 bp linear plasmid was obtained. The method of transformation in this study is electroporation. The selection of K. phaffii transformant was carried out on a selection medium containing zeocin antibiotic. The results showed that K. phaffii transformant clone containing pPICZα-ScFv-anti-EGFRvIII-egfp (5150 bp) recombinant plasmid was succesfully obtained. The selection of K. phaffii transforman with replica platting shows that all selected single colony transformants can grow well at zeocin concentration of 100 μg/mL. The result indicate that the pPICZα-ScFv-anti-EGFRvIII-egfp recombinant plasmid can be integrated into K. phaffii genome stably.

 

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"Latar Belakang : FGF2 merupakan ligan bagi Fibroblast Growth Factor Receptor2(FGFR2). Interaksi dengan reseptor ini memediasi dimerisasi reseptor, fosforilasi, dan aktivasi jalur pensinyalan, seperti jalur Ras-MAPK dan PI3K. Mutasi yang berlebihan melalui sumbu FGF / FGFR dapat menginduksi proliferasi sel kanker, memicu angiogenesis dan limfogenesis, yang mendorong terjadinya metastasis. Penelitian ini mencoba mengevaluasi peran FGF2 pada metastasis kelenjar getah bening aksila pada pasien kanker payudara stadium dini. Tujuan : Mengetahui hubungan nilai ekspresi FGF 2 pada tumor primer terhadap kejadian metastasis kelenjar getah bening aksila. Metode : Digunakan studi potong lintang dengan mengevaluasi ekspresi FGF2 pada 47 pasien kanker payudara stadium dini yang menjalani mastektomi di Rumah Sakit Umum Pusat Nasional Cipto Mangunkusumo (RSCM) pada periode Januari 2014 sampai Desember 2018. Ekspresi FGF2 diperiksa dengan pemeriksaan imunohistokimia, kemudian dievaluasi dan dihubungkan antara ekspresi FGF2 dengan metastasis kelenjar getah bening aksila. Hasil : Uji Chi Square memperlihatkan nilai p=0.044 (p<0.05) yang menunjukkan bahwa terdapat hubungan yang signifikan antara nilai FGF2 pada tumor payudara dengan kejadian metastasis kelenjar getah bening aksila. Odds ratio 4,22 (CI 95% 0,983-18,1). Kesimpulan : Peran FGF2 dalam metastasis kelenjar getah bening berhubungan dengan interaksi antara berbagai faktor limfangiogenik dalam mempromosikan limfangiogenesis dan metastasis limfatik. Ekspresi FGF2 yang tinggi memiliki korelasi signifikan dengan angka kejadian metastasis kelenjar getah bening aksila.

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Background : FGF2 is a ligand for Fibroblast Growth Factor Receptor 2 (FGFR2). Interaction with this receptor mediate dimerization of receptor, phosphorilation, and activation of signaling pathway, such as Ras-MAPK and PI3K. Overmutation through FGF/FGFR induced proliferation of cancer cells, promoted angiogenesis, lymphogenesis, and metastasis. This study tried to evaluate the role of FGF2 in axillary lymph node metastasis in early-stage breast cancer patients.

Aim : To determined the relationship of FGF 2 expression values in primary tumors to the incidence of axillary lymph node metastases.

Methods :A cross-sectional study was used by evaluating the expression of FGF2 in 47 early-stage breast cancer patients who underwent a mastectomy at the Cipto Mangunkusumo National Center General Hospital (RSCM) from January 2014 to Desember 2018. FGF2 expression was examined by immunohistochemistry, then evaluated and linked between expression FGF2 with axillary lymph node metastases.

Results : The Chi Square test had a value of p=0.044 (p<0.05) that showed there was a significant relationship between FGF2 value in breast tumors with the incidence of axillary lymph node metastasis. Odds ratio 4.22 (95% CI 0.983-18.1).

Conclusions The role of FGF2 in lymph node metastasis is related to the interaction between various lymphangiogenic factors in promoting lymphangiogenesis and lymphatic metastasis. High expression of FGF2 has a significant correlation with the incidence of axillary lymph node metastasis."

"[ABSTRAKKanker payudara adalah penyakit multifaktor yang mengakibatkan insiden kematian wanita tertinggi di dunia. Pengobatan kanker payudara berupa pembedahan, radioterapi, dan kemoterapi memiliki efek samping sehingga perlu pengobatan alternatif, salah satunya menggunakan bahan herbal. Daun sirsak (Annona muricata Linn) dilaporkan memiliki efek antitumor dan sitotoksik, tetapi penelitian in vivo terhadap kanker payudara masih sedikit, dibutuhkan penelitian lanjut mengenai efektivitas dan jalur penghambatan daun sirsak terhadap berbagai kanker. Penelitian ini bertujuan untuk mengetahui daya hambat dan dosis efektif ekstrak metanol daun sirsak (Annona muricata Linn) terhadap pertumbuhan tumor payudara mencit C3H secara in vivo. Sebanyak 30 ekor mencit galur C3H yang ditransplan dengan tumor payudara dari mencit C3H donor bertumor, dibagi dalam 5 kelompok perlakuan, yaitu kontrol negatif hanya diberi pelarut CMC 0,5%, kontrol positif diberi doksorubisin, kelompok pemberian ekstrak daun sirsak dosis 15, 30, dan 45 mg/kg BB. Setiap mencit dicekok ekstrak daun sirsak 0,2 cc per hari selama 21 hari, sedangkan kelompok kontrol positif diberikan doksorubisin secara intra vena 0,03 μg/20g BB seminggu sekali selama 21 hari. Panjang dan lebar tumor diukur di awal dan seminggu sekali selama perlakuan untuk mendapatkan data volume tumor. Pada akhir penelitian mencit dinekropsi, tumor mencit ditimbang dan dilakukan pewarnaan AgNOR untuk diukur aktivitas proliferasi sel. Hasil uji Anova menunjukkan perbedaan yang bermakna (p=0,007) antar perlakuan terhadap volume tumor akhir dan terhadap aktivitas proliferasi (p=0,001). Uji Kruskal Wallis terhadap berat tumor menunjukkan tidak ada perbedaan yang bermakna antar perlakuan (p=0,03). Hasil uji korelasi Spearman secara bermakna (p=0,03) menunjukkan ada korelasi positif antara aktivitas proliferasi sel dengan pertumbuhan volume tumor dengan kekuatan korelasi yang lemah (r=0,39). Disimpulkan bahwa ekstrak metanol daun sirsak (Annona muricata Linn) dapat menghambat laju pertumbuhan volume tumor dan aktivitas proliferasi sel kanker payudara mencit C3H dan optimum penghambatan pada dosis 30 mg/kg

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ABSTRACTBB.;Breast cancer is a multifactor disease that has been a leading cause of woman?s mortality. Treatments for breast cancer such as surgery, radiotherapy, and chemotherapy have their own side effects, so that alternative treatments such as herbal medicine are needed. Soursop leaf (Annona muricata Linn) has been reported to have antitumor and cytotoxic effects, but only few conducted in vivo, an advanced research is needed to find the effectiveness and the inhibition pathway of the soursop leaf. The purpose of this research is to find out the inhibition capacity and the effective dose of soursop leaf methanol extract (Annona muricata Linn) against the development of C3H mice?s breast cancer in vivo. There were thirty mice of C3H strain which were transplanted with breast tumor and they were divided into five groups consisting of negative control group which was given only solvent CMC 0.5%, a positive control group which was given doxorubicin, a dose group of 15 mg/kg BB, a dose group of 30 mg/kg BB, and a dose group of 45 mg/kg BB. Each mouse was given 0,2 cc soursop leaf extract every day for 21 days while the positive control group was given doxorubicin 0,03 μg/20 gram BB once a week for 21 days intravenously. The length and the width of the tumor were measured at the beginning and also measured once a week during the experiment process to gain the data of the tumor volume. At the end of the research, the tumor of the mice was lifted and weighed and it was stained by AgNOR to measure the proliferation activity of the cell. The Anova result showed that there was a significant difference (p=0,007) between treatment against the development of tumor which was marked by the decrease of the tumor volume and proliferation activity (p=0,001). The Kruskal Wallis result showed that there was no significant difference (p<0,33) in the tumor weight. Spearman correlation study significantly (p=0,03) indicated that there was a positive correlation between the cell proliferation activity and the growth of the tumor but in a weak correlation (r=0,39). Therefore, it could be concluded that the methanol extract of soursop leaf (Annona muricata Linn) can inhibit the growth rate of tumor volume as well as the proliferation activity of the breast cancer cell of C3H mice and it worked optimally at 30 mg/kg BB dose.;Breast cancer is a multifactor disease that has been a leading cause of woman?s mortality. Treatments for breast cancer such as surgery, radiotherapy, and chemotherapy have their own side effects, so that alternative treatments such as herbal medicine are needed. Soursop leaf (Annona muricata Linn) has been reported to have antitumor and cytotoxic effects, but only few conducted in vivo, an advanced research is needed to find the effectiveness and the inhibition pathway of the soursop leaf. The purpose of this research is to find out the inhibition capacity and the effective dose of soursop leaf methanol extract (Annona muricata Linn) against the development of C3H mice?s breast cancer in vivo. There were thirty mice of C3H strain which were transplanted with breast tumor and they were divided into five groups consisting of negative control group which was given only solvent CMC 0.5%, a positive control group which was given doxorubicin, a dose group of 15 mg/kg BB, a dose group of 30 mg/kg BB, and a dose group of 45 mg/kg BB. Each mouse was given 0,2 cc soursop leaf extract every day for 21 days while the positive control group was given doxorubicin 0,03 μg/20 gram BB once a week for 21 days intravenously. The length and the width of the tumor were measured at the beginning and also measured once a week during the experiment process to gain the data of the tumor volume. At the end of the research, the tumor of the mice was lifted and weighed and it was stained by AgNOR to measure the proliferation activity of the cell. The Anova result showed that there was a significant difference (p=0,007) between treatment against the development of tumor which was marked by the decrease of the tumor volume and proliferation activity (p=0,001). The Kruskal Wallis result showed that there was no significant difference (p<0,33) in the tumor weight. Spearman correlation study significantly (p=0,03) indicated that there was a positive correlation between the cell proliferation activity and the growth of the tumor but in a weak correlation (r=0,39). Therefore, it could be concluded that the methanol extract of soursop leaf (Annona muricata Linn) can inhibit the growth rate of tumor volume as well as the proliferation activity of the breast cancer cell of C3H mice and it worked optimally at 30 mg/kg BB dose.;Breast cancer is a multifactor disease that has been a leading cause of woman?s mortality. Treatments for breast cancer such as surgery, radiotherapy, and chemotherapy have their own side effects, so that alternative treatments such as herbal medicine are needed. Soursop leaf (Annona muricata Linn) has been reported to have antitumor and cytotoxic effects, but only few conducted in vivo, an advanced research is needed to find the effectiveness and the inhibition pathway of the soursop leaf. The purpose of this research is to find out the inhibition capacity and the effective dose of soursop leaf methanol extract (Annona muricata Linn) against the development of C3H mice?s breast cancer in vivo. There were thirty mice of C3H strain which were transplanted with breast tumor and they were divided into five groups consisting of negative control group which was given only solvent CMC 0.5%, a positive control group which was given doxorubicin, a dose group of 15 mg/kg BB, a dose group of 30 mg/kg BB, and a dose group of 45 mg/kg BB. Each mouse was given 0,2 cc soursop leaf extract every day for 21 days while the positive control group was given doxorubicin 0,03 μg/20 gram BB once a week for 21 days intravenously. The length and the width of the tumor were measured at the beginning and also measured once a week during the experiment process to gain the data of the tumor volume. At the end of the research, the tumor of the mice was lifted and weighed and it was stained by AgNOR to measure the proliferation activity of the cell. The Anova result showed that there was a significant difference (p=0,007) between treatment against the development of tumor which was marked by the decrease of the tumor volume and proliferation activity (p=0,001). The Kruskal Wallis result showed that there was no significant difference (p<0,33) in the tumor weight. Spearman correlation study significantly (p=0,03) indicated that there was a positive correlation between the cell proliferation activity and the growth of the tumor but in a weak correlation (r=0,39). Therefore, it could be concluded that the methanol extract of soursop leaf (Annona muricata Linn) can inhibit the growth rate of tumor volume as well as the proliferation activity of the breast cancer cell of C3H mice and it worked optimally at 30 mg/kg BB dose.;Breast cancer is a multifactor disease that has been a leading cause of woman?s mortality. Treatments for breast cancer such as surgery, radiotherapy, and chemotherapy have their own side effects, so that alternative treatments such as herbal medicine are needed. Soursop leaf (Annona muricata Linn) has been reported to have antitumor and cytotoxic effects, but only few conducted in vivo, an advanced research is needed to find the effectiveness and the inhibition pathway of the soursop leaf. The purpose of this research is to find out the inhibition capacity and the effective dose of soursop leaf methanol extract (Annona muricata Linn) against the development of C3H mice?s breast cancer in vivo. There were thirty mice of C3H strain which were transplanted with breast tumor and they were divided into five groups consisting of negative control group which was given only solvent CMC 0.5%, a positive control group which was given doxorubicin, a dose group of 15 mg/kg BB, a dose group of 30 mg/kg BB, and a dose group of 45 mg/kg BB. Each mouse was given 0,2 cc soursop leaf extract every day for 21 days while the positive control group was given doxorubicin 0,03 μg/20 gram BB once a week for 21 days intravenously. The length and the width of the tumor were measured at the beginning and also measured once a week during the experiment process to gain the data of the tumor volume. At the end of the research, the tumor of the mice was lifted and weighed and it was stained by AgNOR to measure the proliferation activity of the cell. The Anova result showed that there was a significant difference (p=0,007) between treatment against the development of tumor which was marked by the decrease of the tumor volume and proliferation activity (p=0,001). The Kruskal Wallis result showed that there was no significant difference (p<0,33) in the tumor weight. Spearman correlation study significantly (p=0,03) indicated that there was a positive correlation between the cell proliferation activity and the growth of the tumor but in a weak correlation (r=0,39). Therefore, it could be concluded that the methanol extract of soursop leaf (Annona muricata Linn) can inhibit the growth rate of tumor volume as well as the proliferation activity of the breast cancer cell of C3H mice and it worked optimally at 30 mg/kg BB dose.;Breast cancer is a multifactor disease that has been a leading cause of woman’s mortality. Treatments for breast cancer such as surgery, radiotherapy, and chemotherapy have their own side effects, so that alternative treatments such as herbal medicine are needed. Soursop leaf (Annona muricata Linn) has been reported to have antitumor and cytotoxic effects, but only few conducted in vivo, an advanced research is needed to find the effectiveness and the inhibition pathway of the soursop leaf. The purpose of this research is to find out the inhibition capacity and the effective dose of soursop leaf methanol extract (Annona muricata Linn) against the development of C3H mice’s breast cancer in vivo. There were thirty mice of C3H strain which were transplanted with breast tumor and they were divided into five groups consisting of negative control group which was given only solvent CMC 0.5%, a positive control group which was given doxorubicin, a dose group of 15 mg/kg BB, a dose group of 30 mg/kg BB, and a dose group of 45 mg/kg BB. Each mouse was given 0,2 cc soursop leaf extract every day for 21 days while the positive control group was given doxorubicin 0,03 μg/20 gram BB once a week for 21 days intravenously. The length and the width of the tumor were measured at the beginning and also measured once a week during the experiment process to gain the data of the tumor volume. At the end of the research, the tumor of the mice was lifted and weighed and it was stained by AgNOR to measure the proliferation activity of the cell. The Anova result showed that there was a significant difference (p=0,007) between treatment against the development of tumor which was marked by the decrease of the tumor volume and proliferation activity (p=0,001). The Kruskal Wallis result showed that there was no significant difference (p<0,33) in the tumor weight. Spearman correlation study significantly (p=0,03) indicated that there was a positive correlation between the cell proliferation activity and the growth of the tumor but in a weak correlation (r=0,39). Therefore, it could be concluded that the methanol extract of soursop leaf (Annona muricata Linn) can inhibit the growth rate of tumor volume as well as the proliferation activity of the breast cancer cell of C3H mice and it worked optimally at 30 mg/kg BB dose.;Breast cancer is a multifactor disease that has been a leading cause of woman’s mortality. Treatments for breast cancer such as surgery, radiotherapy, and chemotherapy have their own side effects, so that alternative treatments such as herbal medicine are needed. Soursop leaf (Annona muricata Linn) has been reported to have antitumor and cytotoxic effects, but only few conducted in vivo, an advanced research is needed to find the effectiveness and the inhibition pathway of the soursop leaf. The purpose of this research is to find out the inhibition capacity and the effective dose of soursop leaf methanol extract (Annona muricata Linn) against the development of C3H mice’s breast cancer in vivo. There were thirty mice of C3H strain which were transplanted with breast tumor and they were divided into five groups consisting of negative control group which was given only solvent CMC 0.5%, a positive control group which was given doxorubicin, a dose group of 15 mg/kg BB, a dose group of 30 mg/kg BB, and a dose group of 45 mg/kg BB. Each mouse was given 0,2 cc soursop leaf extract every day for 21 days while the positive control group was given doxorubicin 0,03 μg/20 gram BB once a week for 21 days intravenously. The length and the width of the tumor were measured at the beginning and also measured once a week during the experiment process to gain the data of the tumor volume. At the end of the research, the tumor of the mice was lifted and weighed and it was stained by AgNOR to measure the proliferation activity of the cell. The Anova result showed that there was a significant difference (p=0,007) between treatment against the development of tumor which was marked by the decrease of the tumor volume and proliferation activity (p=0,001). The Kruskal Wallis result showed that there was no significant difference (p<0,33) in the tumor weight. Spearman correlation study significantly (p=0,03) indicated that there was a positive correlation between the cell proliferation activity and the growth of the tumor but in a weak correlation (r=0,39). Therefore, it could be concluded that the methanol extract of soursop leaf (Annona muricata Linn) can inhibit the growth rate of tumor volume as well as the proliferation activity of the breast cancer cell of C3H mice and it worked optimally at 30 mg/kg BB dose., Breast cancer is a multifactor disease that has been a leading cause of woman’s mortality. Treatments for breast cancer such as surgery, radiotherapy, and chemotherapy have their own side effects, so that alternative treatments such as herbal medicine are needed. Soursop leaf (Annona muricata Linn) has been reported to have antitumor and cytotoxic effects, but only few conducted in vivo, an advanced research is needed to find the effectiveness and the inhibition pathway of the soursop leaf. The purpose of this research is to find out the inhibition capacity and the effective dose of soursop leaf methanol extract (Annona muricata Linn) against the development of C3H mice’s breast cancer in vivo. There were thirty mice of C3H strain which were transplanted with breast tumor and they were divided into five groups consisting of negative control group which was given only solvent CMC 0.5%, a positive control group which was given doxorubicin, a dose group of 15 mg/kg BB, a dose group of 30 mg/kg BB, and a dose group of 45 mg/kg BB. Each mouse was given 0,2 cc soursop leaf extract every day for 21 days while the positive control group was given doxorubicin 0,03 μg/20 gram BB once a week for 21 days intravenously. The length and the width of the tumor were measured at the beginning and also measured once a week during the experiment process to gain the data of the tumor volume. At the end of the research, the tumor of the mice was lifted and weighed and it was stained by AgNOR to measure the proliferation activity of the cell. The Anova result showed that there was a significant difference (p=0,007) between treatment against the development of tumor which was marked by the decrease of the tumor volume and proliferation activity (p=0,001). The Kruskal Wallis result showed that there was no significant difference (p<0,33) in the tumor weight. Spearman correlation study significantly (p=0,03) indicated that there was a positive correlation between the cell proliferation activity and the growth of the tumor but in a weak correlation (r=0,39). Therefore, it could be concluded that the methanol extract of soursop leaf (Annona muricata Linn) can inhibit the growth rate of tumor volume as well as the proliferation activity of the breast cancer cell of C3H mice and it worked optimally at 30 mg/kg BB dose.]"

"Kanker payudara merupakan salah satu jenis kanker dengan kematian terbanyak kedua di dunia. Penyebab utama kematian penderita kanker payudara adalah metastasis sel kanker ke jaringan lain. Salah satu penanganan kanker payudara adalah pemberian pengobatan kemoterapi. Namun kemoterapi seringkali menimbulkan efek samping pada pasien. Salah satu jenis kemoterapi umum, Doxorubicin mampu meningkatkan resiko toksisitas jantung. Karakteristik kultur eksplan yang dapat mempertahankan kondisi sel secara in vivo dapat digunakan untuk memprediksi respons kemoterapi. Namun demikian, penggunaan kultur eksplan untuk memprediksi respon kemoterapi belum banyak diterapkan. Gen MYCN memiliki peran dalam mendorong keganasan sel kanker dan banyak terekspresi pada kanker payudara dengan prognosis buruk, sehingga dapat digunakan sebagai biomarker untuk memastikan respon antara jaringan asal dan kultur eksplan relatif sama. Oleh karena itu penelitian ini bertujuan untuk menganalisis ekspresi gen MYCN pada jaringan asal dan kultur eksplan serta menganalisis tingkat ekspresi gen MYCN pada kultur eksplan terhadap treatment Doxorubicin dengan metode one-step semi-kuantitatif Reverse Transcriptation - Polymerase Chain Reaction (RT-PCR). Perlakuan treatment dilakukan untuk mendukung kemampuan kultur eksplan dalam mempertahankan in vivo. Hasil yang diperoleh menunjukkan ekspresi relatif gen MYCN pada jaringan asal dan kultur eksplan relatif sama serta adanya ekspresi gen MYCN setelah pemberian treatment pada kultur eksplan. Hal tersebut menandakan kultur eksplan dapat mempertahankan ekspresi dari jaringan asalnya. Selain itu, adanya ekspresi gen MYCN setelah pemberian agen kemoterapi mengkonfirmasi bahwa kultur eksplan memiliki respons yang relatif sama setelah pemberian treatment sehingga dapat digunakan untuk memprediksi respon kemoterapi.

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Breast cancer is one type of cancer with the second most deaths in the world. The main cause of death for breast cancer patients is the metastasis of cancer cells to other tissues. One of the treatments for breast cancer is chemotherapy treatment. However, chemotherapy often causes side effects in patients. One of the common types of chemotherapy, Doxorubicin can increase the risk of cardiac toxicity. Characteristics of explant cultures that can maintain cell conditions in vivo can be used predicting chemotherapy response. However, the use of explant cultures to predict chemotherapy response has not been widely applied. The MYCN gene has a role in promoting cancer cell malignancy and is widely expressed in breast cancer with a poor prognosis, so it can be used as a biomarker to ensure that the response between the tissue of origin and explant cultures is relatively similar. Therefore, this study aims to analyze MYCN gene expression in the original tissue and explant culture and to analyze the expression level of the MYCN gene in explant culture against Doxorubicin treatment using a one-step semi-quantitative Reverse Transcriptation - Polymerase Chain Reaction (RT-PCR) method. The treatment was carried out to support the ability of the explant culture to maintain in vivo. The results obtained showed that the relative expression of the MYCN gene in the original tissue and the explant culture was relatively the same as well as the expression of the MYCN gene after the treatment was given to the explant culture. This indicates that the explant culture can maintain the expression of the original tissue. In addition, the presence of MYCN gene expression after administration of chemotherapeutic agents confirmed that explant cultures had relatively the same response after treatment, so that they could be used to predict chemotherapy responses."