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Abstrak :
Latar Belakang: Karsinoma gaster merupakan tumor ganas yang paling sering di daerah gastrointestinal atas. Menurut data epidemiologi adenokarsinoma gaster menunjukkan perkembangan kanker tipe intestinal dan kanker tipe difus melalui jalur kausa yang berbeda dan juga akhir-akhir ini pengobatan terapi target untuk adenokarsinoma telah diketahui dan dikembangkan. Penelitian ini bertujuan untuk mengetahui hubungan antara ekspresi HER2 dengan tipe histopatologik menurut klasifikasi Lauren dan derajat diferensiasi pada adenokarsinoma gaster. Bahan dan cara kerja: Penelitian dilakukan di Departemen Patologi Anatomik FKUI RSCM Jakarta, dengan melakukan analisis ekspresi HER2 untuk melihat hubungannya dengan tipe histopatologik dan derajat diferensiasi adenokarsinoma gaster yang diperoleh secara reseksi dan biopsi sejak tahun 2007-2011. Penilaian tipe histopatologik dengan menggunakan pulasan Hematoxillin Eosin dan penilaian ekspresi HER2 dengan menggunakan pulasan imunohistokimia HER2. Hasil: Dari tahun 2007-2011 diperoleh 55 kasus (76,4% laki-laki dan 23,6% wanita). Rata-rata umur penderita 50,55 tahun (rentang umur 29-73 tahun). Ekspresi HER2 3+, 2+, dan 1+ didapatkan pada 14,5%, 34,5%, dan 25,5% sampel. Sebanyak 25,5% sampel tidak menunjukkan ekspresi HER2. Ekspresi berlebih HER2 (3+) didapatkan pada 8 kasus (14,5%) adenokarsinoma gaster, yang seluruhnya adalah tipe intestinal . Kesimpulan: Terdapat hubungan yang bermakna antara ekspresi HER2 dengan tipe histopatologik (p= 0,021). Tidak terdapat hubungan yang bermakna antara ekspresi HER2 dengan derajat diferensiasi tumor (p=0,253).

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Background: Gastric carcinoma is the most common malignant tumor in upper gastrointestinal. According to epidemiologic data, gastric adenocarcinoma intestinal type and diffuse type showed different carcinogenesis. Recently, targeting therapy for adenocarcinoma has established. The aim of the study to know the relationship between HER2 expression and histopathologic type according to Lauren's classification and grading of gastric adenocarcinoma. Patient and method: This study has done in Anatomical Pathology department of medicine University Indonesia/ Cipto Mangunkusumo National Hospital, Jakarta. HER2 expression is analyzed to see the relationship with histopathologic type and differentiation of gastric adenocarcinoma. The specimens were from resection and biopsy (2007-2011). Histopathologic type evaluated with Hematoxylin Meyer's staining. HER2 expression evaluated with immunostaining with HER2 antibody. Results: We found 55 cases from 2007 until 2011 (76,4% men and 23,6% women). The mean age is 50,55 years (the range of age 29-73 years). HER2 expression 3+,2+ and 1+ are 14,5%, 34,5%, and 25,5% sampling. 25% sample did not show HER2 expression. We found overexpression HER2 (3+) in 8 cases (14,5%) of adenocarcinoma gastric intestinal type. Conclusion: There is a significant relation between HER2 expression with histopathologic type (p=0,021). There is no significant relation between HER2 with grading (p=0,253).

Abstrak :
Latar Belakang: CXCR4 adalah reseptor kemokin G-protein 7-transmembran yang diekspresikan pada beberapa sel kanker payudara manusia pada tumor payududara primer dan metastasis yang menyebabkan migrasi sel hematopoietik dari sumsum tulang belakang ke kelenjar getah bening perifer. Penelitian-penelitian sebelumnya menunjukkan bahwa CXCR4 berkaitan dengan metastasis kelenjar getah bening aksilla. Namun, sampai sekarang, tidak ditemukan penelitian yang mengevaluasi peran CXCR4 dalam metastasis kelenjar getah bening sentinel pada kanker payudara stadium dini. Tujuan: Menentukan peran reseptor kemokin CXCR4 pada migrasi sel kanker payudara ke kelenjar getah bening sentinel. Metode: Digunakan desain studi potong lintang dengan mengevaluasi ekspresi CXCR4 pada 32 pasien kanker payudara stadium dini yang menjalani mastektomi di Rumah Sakit Umum Pusat Nasional Cipto Mangunkusumo (RSCM) pada periode Maret sampai Juni 2016. Pada seluruh kasus, ekspresi CXCR4 diperiksa dengan pemeriksaan imunohistokimia. Kemudian, dievaluasi hubungan antara ekspresi CXCR4 dengan metastasis kelenjar getah bening sentinel. Hasil: Ekspresi CXCR4 yang tinggi (cut off point ≥ 5) terdeteksi pada 19 dari 32 (59.4%) pasien kanker payudara stadium dini. Dari 19 pasien dengan metastasis kelenjar getah bening sentinel, 16 (84.21%) pasien memiliki ekspresi CXCR4 yang tinggi. Ekspresi CXCR4 berkorelasi signifikan dengan metastasis kelenjar getah bening (p < 0.01). Kesimpulan: Ekspresi CXCR4 yang tinggi berkorelasi signifikan dengan metastasis kelenjar getah bening sentinel pada pasien kanker payudara stadium dini. ......Background: CXCR4 is a 7-transmembrane G-protein chemokine receptor expressed in some human breast cancer cells in both primary breast tumors and metastases that allows for migration of hematopoietic cells from the bone marrow to the peripheral lymph nodes. Previous studies have shown that CXCR4 is associated with axillary lymph node metastases. However, up until now, no studies evaluating the role of CXCR4 in sentinel lymph node metastases in early stage breast cancer patients were found. Aim: To determine the role of chemokine receptor CXCR4 in breast cancer cells migration to sentinel lymph nodes. Methods: A cross sectional study design was used by evaluating CXCR4 expression of 32 early stage breast cancer patients that underwent mastectomy in Cipto Mangunkusumo Hospital during the period of March to June 2016. CXCR4 expression was assessed by immunohistochemistry in all cases. Associations between CXCR4 expressions and sentinel lymph node metastases were evaluated. Results: High CXCR4 expression (cut off point ≥ 5) was dectected in 19 of 32 (59.4%) primary early stage breast cancer patients. Of 19 patients with sentinel lymph node metastases, 16 (84.21%) had high expression of CXCR4. The expression of CXCR4 is significantly associated with sentinel lymph node metastases (p < 0.01). Conclusions: High expression of CXCR4 was significantly correlated with sentinel lymph node metastases in early stage breast cancer patients.

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ABSTRAK
Latar belakang : Beberapa penelitian terakhir menunjukkan infiltrasi masif dari monosit berhubungan dengan resiko berat badan lahir rendah pada janin. CD 68 dapat digunakan untuk mendeteksi sel inflamasi monosit/makrofag dalam melihat respon imunitas maternal dalam melawan infeksi malaria dalam kehamilan. Tujuan penelitian ini untuk mengetahui ekspresi CD 68 berdasarkan kriteria histopatologik malaria plasenta. Metode : Studi potong lintang jaringan biopsi plasenta dengan diagnosis histopatologik akut, kronik, lama dan non infeksi. Sampel penelitian dipulas dengan pewarnaan imunohistokimia CD 68, diidentifikasi, dan dianalisa hubungan ekspresi CD 68 berdasarkan diagnosis histopatologik, inflamasi monosit dan berat badan lahir.Hasil : Ekspresi CD 68 positif dengan nilai rata-rata 0,91 0,62. Ekspresi CD 68 lebih tinggi pada malaria plasenta akut dibandingkan dengan kelompok lainnya dengan nilai rata-rata 1,66 0,35 . Ekspresi CD 68 pada inflamasi monosit sedang lebih tinggi dibandingkan dengan inflamasi monosit minimal p = 0,033 . Tidak didapatkan hubungan bermakna antara CD 68 dengan berat badan lahir bayi p = 0,574 . Kesimpulan : Ekspresi CD 68 positif umumnya pada malaria plasenta akut dan inflamasi sedang, yang dapat mempengaruhi prognosis dan terapi.

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ABSTRACT
Background Several recent studies have shown that massive infiltration of monocytes is associated with low birth weight risk. CD 68 can be used to detect monocyte macrophage inflammatory cells in view of the response of maternal immunity against malarial infections in pregnancy. The aim of this study was to determine the expression of CD 68 based on histopathologic criteria of placental malaria. Objective Cross sectional study of placental biopsy tissue with histopathological diagnosis as acute, chronic, long and non infectious. The study sample was stained with CD 68 antibody and analyzed the association of expression CD 68 with histopathologic diagnosis, monocyte inflammation and birth weight. Results CD 68 expression was positive with mean score was 0.91 0.62. CD 68 expression was higher in acute placental malaria compared with other groups mean, 1.66 0.35 . CD 68 expression on monocyte inflammation was higher than on minimal monocyte inflammation p 0.033 . There was significant correlation between histopathological diagnosis with monocyte inflammation p 0,025 . There was no significant association between CD 68 and birth weight p 0,574 . Conclusion Positive CD expression 68 is common in acute placental malaria and mild inflammation, which may affect prognosis and therapy. Keywords CD expression 68 placental malaria histopathologic diagnosis immune system

Abstrak :
Tesis ini bertujuan mengukur kedalaman kerusakan jaringan serviks normal pasca aplikasi topikal dosis tunggal Trichlor-Acetic Acid (TCA) 85 persen. Desain penelitian adalah intervensi dengan mengoleskan ±5 mL larutan TCA 85% pada serviks 40 orang subjek yang terjadwal menjalani prosedur histerektomi total atas indikasi selain patologi serviks 24 jam sebelum operasi. Kedalaman kerusakan jaringan diukur secara mikroskopis pada foto preparat histologi spesimen serviks. Hasil penelitian ini didapatkan dari total 39 subjek. Gambaran mikroskopis ditemukan area nekrosis lapisan superfisial disertai erosi seluruh ketebalan epitel skuamosa. Ditemukan juga area fibrotik mirip jaringan luka bakar pada stroma. Rata-rata kedalaman kerusakan jaringan serviks di bibir anterior adalah 1,16 ± 0,49 mm dan posterior 1,01 ± 0,35 milimeter. Tidak terdapat perbedaan signifikan antara kedalaman di bibir anterior dan posterio (p³0,05). Sebagai kesimpulan, aplikasi topikal dosis tunggal larutan TCA 85% mampu menimbulkan kerusakan jaringan serviks normal dengan kedalaman yang lebih dalam daripada rata-rata kedalaman lesi NIS III di epitel skuamosa serviks. ......This study aims to measure the depth of destruction to normal cervical tissue after topical application of a single dose of 85 percent Trichlor-Acetic Acid (TCA). The study design was interventional by applying ±5 mL of 85% TCA solution to the cervix of 40 subjects who were scheduled to undergo a total hysterectomy procedure for indications other than cervical pathology 24 hours before surgery. The depth of tissue destruction was measured microscopically on histological photographs of cervical specimens. The results of this study were obtained from a total of 39 subjects. The microscopic picture found areas of superficial layer necrosis accompanied by full thickness erosion of the squamous epithelium. There were also fibrotic areas resembling burnt tissue in the stroma. The mean depth of cervical tissue destruction in the anterior lip was 1.16 ± 0.49 mm and the posterior 1.01 ± 0.35 mm. There was no significant difference between the depth in the anterior and posterior lips (p³0.05). In conclusion, topical application of a single dose of 85% TCA solution was able to cause destruction to normal cervical tissue with a deeper depth than the average CIN III depth in cervical squamous epithelium.

Abstrak :
Kanker ovarium merupakan penyakit ginekologi terbanyak ketiga setelah kanker payudara dan kanker serviks. Kanker ovarium epitelial merupakan tipe paling banyak, dibedakan menjadi low-grade dan high-grade. Faktor kerentanan genetik yang diduga dapat meningkatkan risiko kanker ovarium adalah gen AKNA yang berperan pada respon imun, inflamasi, Epithelial-Mesenchymal Transition (EMT). Penelitian ini bertujuan mengetahui distribusi varian promotor gen AKNA rs10817595 dan ekspresinya tingkat mRNA dan protein pada kanker ovarium epitelial. Sebanyak 63 sampel kanker ovarium dan 65 kontrol digunakan untuk analisis distribusi genotipe dan alel AKNA menggunakan T-ARMS PCR, 35 sampel low-grade, 28 sampel high- grade dianalisis ekspresi mRNA menggunakan qRT-PCR dan dianalisis korelasinya dengan genotipe AKNA. Sebanyak 15 sampel low-grade, 12 sampel high-grade dianalisis level protein AKNA menggunakan imunohistokimia dan dianalisis korelasinya dengan level mRNA AKNA. Hasil penelitian menunjukkan tidak ada perbedaan signifikan frekuensi distribusi genotipe dan alel AKNA, perbedaan signifikan ekspresi mRNA AKNA dan korelasi signifikan ekspresi relatif mRNA AKNA dengan genotipe AKNA, perbedaan signifikan level protein AKNA pada kelompok low-grade, high-grade dibanding kista, tidak ditemukan korelasi signifikan ekspresi relatif mRNA AKNA dengan level protein. Disimpulkan bahwa varian promotor gen AKNA dapat menyebabkan penurunan level mRNA dan protein kelompok low-grade dan high-grade sehingga berpotensi sebagai faktor kerentanan genetik pada kanker ovarium epitelial. ......Ovarian cancer is the third highest gynecological disease after breast and cervical cancer. Epithelial ovarian cancer is common type, divided into low-grade and high- grade. Genetic susceptibility factor that is thought to increase ovarian cancer risk is AKNA gene which plays a role in immune response, inflammation, Epithelial- Mesenchymal Transition (EMT). This study aims to determine the distribution of AKNA (rs10817595) variant gene promotor, its mRNA and protein level in epithelial ovarian cancer. 63 ovarian cancer and 65 controls were used for genotyping using T- ARMS PCR, 35 low-grade and 28 high-grade samples were analyzed for mRNA levels using qRT-PCR and for correlation with AKNA genotype. 15 low-grade and 12 high- grade samples were analyzed for AKNA protein levels using immunohistochemistry and for correlation with AKNA mRNA levels. The results showed that there was no significant difference in AKNA genotypes and alleles, significant differences in mRNA level and significant correlations between mRNA level with AKNA genotypes, significant differences in AKNA protein levels, and no significant correlation of mRNA with protein levels in low-grade, high-grade compared to cyst. Concluded that AKNA gene promotor variant can cause a decrease in mRNA and protein levels in the low-grade and high-grade, it has the potential as one of genetic susceptibility factor for epithelial ovarian cancer.

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[ABSTRAK
Tujuan: Menentukan hubungan obesitas dengan proporsi ukuran tumor, keterlibatan KGB aksila dan derajat histopatologi pada pasien kanker payudara stadium I – IIIA di RSUPNCM, serta membantu meningkatkan kualitas tatalaksana bagi klinisi. Metode: Analisa menggunakan data sekunder pada pasien kanker payudara stadium I – III A. Dikatan obesitas bila indeks massa tubuh ≥ 25 kg/m2 dan non obesitas < 25 kg/m2. Hasil ukuran tumor dikelompokkan menjadi < 2 cm, 2-5 cm dan > 5 cm berdasarkan sistem staging TNM AJCC. Ukuran tumor diperoleh melalui pencitraan ultrasonografi payudara yang tersimpan pada sistem PACS. Keterlibatan KGB aksila serta derajat histopatologi diperoleh dari hasil ekspertise patologi anatomi. Hasil: Jumlah subyek penelitian sebanyak 52 pasien kanker payudara stadium I– IIIA tahun 2012 - 2014 di RSUPNCM terdiri dari 26 pasien obesitas dan 26 pasien non obesitas. Tidak ada hubungan yang bermakna antara ukuran tumor berdasarkan staging dengan obesitas (P= 0,795 (uji chi square)). Tidak terdapat hubungan yang bermakna antara obesitas dengan derajat histopatologi (P=0,610, (uji mutlak fisher)). Tidak terdapat hubungan yang bermakna antara obesitas dan keterlibatan KGB aksila (P =0,404 (uji chi square)). Median ukuran tumor pada pasien obesitas 2,95 cm dan pasien non obesitas 2,73 cm. Dari 26 pasien obesitas, 25 diantaranya memiliki derajat tinggi. Dari 26 pasien non obesitas, 14 memiliki keterlibatan KGB aksila. Kesimpulan: Pasien kanker payudara yang obesitas tidak berhubungan dengan besarnya ukuran tumor, keterlibatan KGB aksila dan derajat histopatologi yang tinggi. Namun terdapat kecenderungan pasien kanker payudara yang obesitas memiliki ukuran tumor yang lebih besar dan tingginya derajat histopatologi. Sedangkan keterlibatan KGB aksila lebih cenderung pada pasien yang non obesitas.

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ABSTRACT
Objective: Determine the relationship of obesity with tumor size proportion, axillary lymph node involvement and histopathological grading in breast cancer patients stage I-IIIA in Cipto Mangunkusomo hospital and to help improvement the quality of management by clinician. Methods: Analysis using secondary data of breast cancer patient stage I-IIIA. Obesity grouped if body mass index ≥ 25 kg/m2 and non obese < 25 kg/m2. The results of tumor size are grouped into 0-2 cm, 2-5 cm and > 5 cm based on the AJCC TNM staging system. Tumor size obtained through breast ultrasound imaging from PACS system. Axillary lymph node involvement and histopathological grading obtained from the anatomical pathology expertise. Results: The study subjects are 52 patients with stage I-IIIA breast cancer in 2012-2014 in Cipto Mangunkusumo consisted of 26 obese and 26 non-obese patients. There is no significant relationship between tumor size based on staging with obesity (P = 0.795 (chi square test)). There was no significant relationship between obesity and grading histopathology (P = 0.610, (absolute test fisher)). There was no significant relationship between obesity and the involvement of axillary lymph nodes (P = 0.404 (chi square test)). The median tumor size of 2.95 cm in obese patients and 2,73 cm in non-obese patients. From 26 obese patients, 25 of them had a high grading histopathology. From 26 non-obese patients, 14 of them had involvement of axillary lymph nodes. Conclusion: Breast cancer patients who are obese are not related to the larger tumor size , involvement of axillary lymph nodes and a high grading of histopathology. However, there is a tendency that breast cancer patients who are obese had larger tumor size and high grading of histopathology. Where as the involvement of axillary lymph nodes are more likely in non-obese patients., Objective: Determine the relationship of obesity with tumor size proportion, axillary lymph node involvement and histopathological grading in breast cancer patients stage I-IIIA in Cipto Mangunkusomo hospital and to help improvement the quality of management by clinician. Methods: Analysis using secondary data of breast cancer patient stage I-IIIA. Obesity grouped if body mass index ≥ 25 kg/m2 and non obese < 25 kg/m2. The results of tumor size are grouped into 0-2 cm, 2-5 cm and > 5 cm based on the AJCC TNM staging system. Tumor size obtained through breast ultrasound imaging from PACS system. Axillary lymph node involvement and histopathological grading obtained from the anatomical pathology expertise. Results: The study subjects are 52 patients with stage I-IIIA breast cancer in 2012-2014 in Cipto Mangunkusumo consisted of 26 obese and 26 non-obese patients. There is no significant relationship between tumor size based on staging with obesity (P = 0.795 (chi square test)). There was no significant relationship between obesity and grading histopathology (P = 0.610, (absolute test fisher)). There was no significant relationship between obesity and the involvement of axillary lymph nodes (P = 0.404 (chi square test)). The median tumor size of 2.95 cm in obese patients and 2,73 cm in non-obese patients. From 26 obese patients, 25 of them had a high grading histopathology. From 26 non-obese patients, 14 of them had involvement of axillary lymph nodes. Conclusion: Breast cancer patients who are obese are not related to the larger tumor size , involvement of axillary lymph nodes and a high grading of histopathology. However, there is a tendency that breast cancer patients who are obese had larger tumor size and high grading of histopathology. Where as the involvement of axillary lymph nodes are more likely in non-obese patients.]

Abstrak :
Latar belakang: Kanker payudara merupakan kanker terbanyak dengan insiden 40,3 per 100.000 perempuan dan angka mortalitas sebesar 16,6 per 100.000 perempuan di Indonesia. Pada stadium awal I-II, penentuan terapi operatif mastektomi seringkali membutuhkan pemeriksaan potong beku intraoperatif untuk menilai keganasan, namun sering tidak tersedia di banyak rumah sakit. Tripel diagnostik pemeriksaan fisik, ultrasonografi dan fine needle aspiration biopsy merupakan metode diagnostik preoperatif yang juga dinilai akurat dan mudah dilakukan. Studi ini menilai kesesuaian tripel diagnostik dengan histopatologis khususnya pada benjolan yang curiga ganas di RSCM dan RSUPP selama Februari 2016-Agustus 2017. Metode: Subjek dengan benjolan payudara curiga ganas pada stadium awal yang memenuhi kriteria inklusi di RSCM dan RSUPP dilakukan tripel diagnostik preoperatif, kemudian dilakukan pemeriksaan potong beku intraoperatif dan histopatologi pasca operasi. Menggunakan desain studi diagnostik statistik, dilakukan analisis kesesuaian tripel diagnostik maupun potong beku dibandingkan dengan histopatologi yaitu sensitivitas, spesifisitas, nilai prediksi positif NPP, nilai prediksi negatif NPN dan akurasi. Hasil Didapatkan 33 subjek kanker payudara stadium awal prevalensi 4,3 dengan rerata umur 49,6 tahun dengan kelompok umur terbanyak di atas 40 tahun 78,8. Sekitar 63,6 subjek memiliki ukuran tumor 2-5 cm dan jenis histopatologi terbanyak berupa karsinoma invasif 84,8. Dibandingkan hasil histopatologi: a Potong beku memiliki sensitivitas 96,8, spesifisitas 100, NPP 100, NPN 66,7, dan akurasi 97,0 ; dan b Tripel diagnostik mempunyai sensitivitas 77,4, spesifisitas 100, nilai prediksi positif tinggi 100, nilai prediksi negatif 22,2 dan akurasi 78,8 p = 0,016. Kesimpulan: Tripel diagnostik merupakan metode diagnostik yang cukup akurat pada kanker payudara stadium awal sehingga dapat digunakan sebagai metode diagnostik alternatif di fasilitas pelayanan tipe C dan D di Indonesia di saat potong beku tidak tersedia. ...... Background: Breast cancer is the most common cancer with incidence rate 40.3 per 100.000 women and mortality rate 16.6 per 100.000 women in Indonesia. In early stage, decision for operative therapy mastectomy requires intraoperative frozen section to assess its malignancy, which is often unavailable in many hospitals. Triple diagnostic physical examination, breast ultrasonography and fine needle aspiration biopsy is an accurate and easily performed preoperative diagnostic method. This study assesses the suitability of triple diagnostic with histopathology results in suspicious malignant breast lumps at Ciptomangunkusumo and Persahabatan hospital during February 2016 August 2017. Method: Subjects with supicious malignant breast lump that met the inclusion criteria underwent preoperative triple diagnostic, intraoperative frozen section and postoperative histopathology examination. With statistic diagnostic study design, the suitability of triple diagnostic and frozen section were assesed in comparation to histologic examination sensitivity, specificity, positive predictive value PPV, negative predictive value NPV and accuracy. Result: 33 subjects with early stage breast cancer were obtained prevalence 4.3 with average mean of age of 49.6 years, were above 40 years 78.8. Around 63.6 had tumor size between 2 5 cm, and most histopathologic types were those with invasive carcinoma 84.8. When compared to histopathologic result a Frozen section has 96.8 sensitivity, 100 specificity, 100 PPV, 66.7 NPV and 97.0 accuracy and b Triple diagnostic has 77.4 sensitivity, 100 specificity, high PPV 100, 22.2 NPV and 78.8 accuracy. p 0.016. Conclusion: Triple diagnostic is a relatively accurate diagnostic method in early stage breast cancer, hence, can be used as an alternative diagnostic method at type C and D heatlhcare facilities in Indonesia whenever frozen section is unavailable.

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Tujuan: PD-L1 merupakan protein yang berperan dalam pengaturan respon imun terhadap tumor. Peningkatan ekspresi PD-L1 mengakibatkan antigen atau sel kanker dapat terhindar dari sistem imun. Hubungan ekspresi PD-L1 dengan penggunaan imunoterapi dan radioterapi secara bersamaan telah banyak dilakukan. Akan tetapi, saat ini masih belum diketahui hubungan antara ekspresi tersebut dengan toksisitas akut radiasi. Untuk itu, penelitian ini dilakukan untuk mengevaluasi hubungan antara ekspresi PD-L1 dengan toksisitas akut selama radiasi dan 2 bulan paska radiasi. Metoda: 30 pasien kanker serviks lanjut local yang mendapatkan terapi radiasi di Departemen radioterapi RSCM. Pasien dilakukan biopsy 2 kali yaitu pra radiasi eksterna dan paska radiasi eksterna untuk dilakukan pemeriksaan ELISA & IHK PD-L1. Selama menjalani radiasi eksterna dan 2 bulan paska radiasi, pasien dievaluasi toksisitas akut dengan kirteria CTCAE versi 5. Hasil: Ekspresi PD-L1 pada kanker serviks lanjut lokal yang mendapatkan radiasi tidak memengaruhi pada toksisitas akut selama radiasi eksterna dan 2 bulan paska radiasi (p>0,05). Akan tetapi, IHK PD-L1 dengan intesitas ≥ 2 dan ELISA PD-L1 yang mengalami penurunan dari pra radiasi ke paska radiasi, menunjukkan ada kecenderungan memiliki toksisitas yang lebih rendah yaitu ≤ Grade 1. Kesimpulan: Ekspresi PD-L1 tidak menurunkan toksisitas akut radiasi selama radiasi dan 2 bulan paska terapi pada pasien kanker serviks stadium lanjut lokal. Akan tetapi, pada toksisitas akut 2 bulan paska terapi menunjukkan kecenderungan mendapatkan toksisitas radiasi yang lebih rendah pada pasien yang memiliki ekspresi PD-L1. ......Objectives: PD-L1 is a protein that controls the immune response to tumors. Increased PD-L1 expression results in immune system not detecting cancer cells. There was a correlation between the expression of PD-L1 and the combined use of immunotherapy and radiotherapy. At this time, however, there is no established association between these expression and radiation acute toxicity. Methods: Totally 30 locally advanced cervical cancer patients receiving radiation therapy in the Department of Radiotherapy of RSCM. Biopsy was performed twice, pre-external radiation and post-external radiation for PD-L1 ELISA & IHC tests. The patient was evaluated for radiation of acute toxicity with CTCAE version 5 during external radiation and 2 months post-radiation. Results: The expression of PD-L1 in local advanced cervical cancer which received radiation did not affect acute toxicity during external radiation and 2 months post radiation (p > 0.05). However, PD-L1 CPI with intensity ≥ 2 and PD-L1 ELISA which decreased from pre-radiation to post-radiation, showed a tendency to have lower toxicity, namely ≤ Grade 1. Conclusion: PD-L1 expression in local advanced cervical cancer patients did not reduce the acute toxicity of radiation during external radiation and 2 months post-treatment. Nonetheless, 2 months post-therapy, acute toxicity showed a propensity to lower toxicity in patients with expression of PD-L1.

Abstrak :
Tujuan: PD-L1 merupakan protein yang berperan dalam pengaturan respon imun terhadap tumor. Peningkatan ekspresi PD-L1 mengakibatkan antigen atau sel kanker dapat terhindar dari sistem imun. Hubungan ekspresi PD-L1 dengan penggunaan imunoterapi dan radioterapi secara bersamaan telah banyak dilakukan. Akan tetapi, saat ini masih belum diketahui hubungan antara ekspresi tersebut dengan toksisitas akut radiasi. Untuk itu, penelitian ini dilakukan untuk mengevaluasi hubungan antara ekspresi PD-L1 dengan toksisitas akut selama radiasi dan 2 bulan paska radiasi. Metoda: 30 pasien kanker serviks lanjut local yang mendapatkan terapi radiasi di Departemen radioterapi RSCM. Pasien dilakukan biopsy 2 kali yaitu pra radiasi eksterna dan paska radiasi eksterna untuk dilakukan pemeriksaan ELISA & IHK PD-L1. Selama menjalani radiasi eksterna dan 2 bulan paska radiasi, pasien dievaluasi toksisitas akut dengan kirteria CTCAE versi 5. Hasil: Ekspresi PD-L1 pada kanker serviks lanjut lokal yang mendapatkan radiasi tidak memengaruhi pada toksisitas akut selama radiasi eksterna dan 2 bulan paska radiasi (p>0,05). Akan tetapi, IHK PD-L1 dengan intesitas ≥ 2 dan ELISA PD-L1 yang mengalami penurunan dari pra radiasi ke paska radiasi, menunjukkan ada kecenderungan memiliki toksisitas yang lebih rendah yaitu ≤ Grade 1. Kesimpulan: Ekspresi PD-L1 tidak menurunkan toksisitas akut radiasi selama radiasi dan 2 bulan paska terapi pada pasien kanker serviks stadium lanjut lokal. Akan tetapi, pada toksisitas akut 2 bulan paska terapi menunjukkan kecenderungan mendapatkan toksisitas radiasi yang lebih rendah pada pasien yang memiliki ekspresi PD-L1. ......Objectives: PD-L1 is a protein that controls the immune response to tumors. Increased PD-L1 expression results in immune system not detecting cancer cells. There was a correlation between the expression of PD-L1 and the combined use of immunotherapy and radiotherapy. At this time, however, there is no established association between these expression and radiation acute toxicity. Methods: Totally 30 locally advanced cervical cancer patients receiving radiation therapy in the Department of Radiotherapy of RSCM. Biopsy was performed twice, pre-external radiation and post-external radiation for PD-L1 ELISA & IHC tests. The patient was evaluated for radiation of acute toxicity with CTCAE version 5 during external radiation and 2 months post-radiation. Results: The expression of PD-L1 in local advanced cervical cancer which received radiation did not affect acute toxicity during external radiation and 2 months post radiation (p > 0.05). However, PD-L1 CPI with intensity ≥ 2 and PD-L1 ELISA which decreased from pre-radiation to post-radiation, showed a tendency to have lower toxicity, namely ≤ Grade 1. Conclusion: PD-L1 expression in local advanced cervical cancer patients did not reduce the acute toxicity of radiation during external radiation and 2 months post-treatment. Nonetheless, 2 months post-therapy, acute toxicity showed a propensity to lower toxicity in patients with expression of PD-L1.

Abstrak :
Latar Belakang : Kanker serviks stadium awal dapat ditatalaksana dengan baik, namun pada stadium lanjut lokal memiliki prognosis yang buruk. Terapi standar yang tersedia masih kurang optimal dan memiliki efek samping yang mengganggu. Pada keadaan tertentu tumor dapat mengalami metastases atau progresif, salah satunya karena adanya ikatan PD-L1 dengan sel limfosit T sehingga kanker serviks terhindar dari respon imun. Pemberian anti PD-L1 menjadi bagian yang penting dalam pengobatan imunoterapi kanker. Di Indonesia belum tersedia data empirik profil karakteristik yang berkaitan dengan ekspresi PD-L1 serta respon tumor terhadap radiasi pada kanker serviks. Metode: Penelitian ini memeriksa ekspresi PD-L1 intratumoral pada jaringan biopsi karsinoma sel skuamosa serviks pre dan paska radiasi eksterna dengan menggunakan metode ELISA dan IHK, pemeriksaan IHK menggunakan antibodi clone 28-8 dari Abcam. Pemeriksaan CT scan evaluasi sebelum radiasi dan 2 bulan setelah radiasi dipakai sebagai alat untuk menilai respon terapi radiasi. Hasil : Dari 31 pasien yang ikut serta, terdapat 29 pasien yang telah dilakukan pemeriksaan ekspresi PD-L1 sebelum dan sesudah radiasi, selanjutnya hanya 22 pasien yang telah menjalani CT scan evaluasi. Ekspresi PD-L1 ELISA paska radiasi eksterna berbeda bermakna pada tumor berukuran ≥5cm (p=0,015) dan ekspresi PD-L1 IHK berbeda bermakna pada sel tumor berkeratin (p=0,023), pada pasien dengan grade IHK yang difus (+3) resiko relatif untuk respon komplit 0,5 kali dibandingkan dengan grade IHK yang  tidak difus. Uji korelasi perbedaan selisih ekspresi (delta) dan rasio PD-L1 ELISA menunjukkan tidak ada korelasi (R2= 0,217) dan (R2= 0,194) terhadap respons, begitu juga hasil pada hasil pemeriksaan ekspresi PD-L1 IHK tidak ada perbedaan bermakna pada kategori kenaikan, tetap dan penurunan, tetapi ketika kategori dirubah menjadi penurunan dan tidak ada penurunan didapatkan nilai p yang lebih baik (p=0,161 vs p=.0,613). Kesimpulan : Tidak terdapat perbedaan bermakna antara ekspresi PD-L1 pre dan paska radiasi terhadap respon, akan tetapi terdapat tren penurunan kadar PD-L1 IHK berkaitan dengan respon terapi. ......Correlation of Intratumoral PD-L1 Expression Before and After External Radiation to The Radiation Response in Locally Advanced Cervical Cancer. Background: Early-stage cervical cancer can be managed properly, but at a locally advanced stage it has a poor prognosis. The standard therapy available is still suboptimal and has disturbing side effects. In certain circumstances, tumors can undergo metastases or progressives, one of which is due to the binding of PD-L1 with T lymphocyte cells so that cervical cancer is protected from the immune response. In Indonesia, there is no available empirical data on the characteristic profiles related to PD-L1 expression and tumor response to radiation in cervical cancer. Method: This study examined intratumoral PD-L1 expression in biopsy tissue of squamous cell carcinoma of cervical cells pre and post external radiation using ELISA and IHC methods, IHC examination using antibody clone 28-8 from Abcam. CT scan evaluation before radiation and 2 months after radiation are used as a tool to assess the response of radiation therapy. Results: Of the 31 patients who participated, there were 29 patients who had examined the expression of PD-L1 before and after radiation, then only 22 patients who had undergone a CT scan evaluation. Expression of PD-L1 ELISA after external radiation was significantly different in tumors of ≥5cm (p=0.015) and expression of PD-L1 IHC was significantly different in keratinous tumor cells (p = 0.023), in patients with diffuse IHC grade (+3) relative risk to complete response of 0.5 times compared to the grade of IHC which is not diffuse. Correlation test difference in expression difference (delta) and PD-L1 ELISA ratio showed no correlation (R2=0.217) and (R2=0,194) to the response, as well as results on the examination results of PD-L1 IHC expression there was no significant difference in the increased category, constant and decrease, but when the category is changed to decrease and there is no decrease, a better p-value is obtained (p=0.161 vs p=0.613). Conclusion: There was no significant difference between the expression of PD-L1 pre and post-radiation to the response, but there was a trend of decreasing PD-L1 IHC levels concerning therapeutic response.