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"[ABSTRAKLatar Belakang: Karsinoma papiler tiroid (KPT) merupakan keganasan terseringorgan endokrin dengan prognosis yang sangat baik, namun pada beberapa kasusdapat terjadi rekurensi dan mortalitas. Beberapa faktor prognostik dan mutasi Btyperapidly accelerated fibrosarcoma V600E (BRAF V600E) dikatakanberhubungan dengan prognosis yang lebih buruk. Pemeriksaan imunohistokimiaprotein BRAF V600E dipercaya dapat mendeteksi adanya mutasi denganspesifisitas 100% dan sensitivitas 89%. Tujuan penelitian ini untuk mengetahuiimunoekspresi BRAF V600E dan hubungannya dengan faktor-faktor prognostik.Bahan dan Cara: Penelitian dilakukan secara retrospektif, desain deskriptifanalitik studi potong lintang. Sampel penelitian berasal dari RSCM berjumlah 50kasus KPT yang dinilai ulang untuk menentukan faktor-faktor prognostik secaramikroskopik. Pemeriksaaan mutasi BRAF V600E menggunakan tehnikimunohistokimia dan penilaian menggunakan H score.Hasil: Nilai H score ³ 326,5 ditentukan sebagai mutasi BRAF V600E positif dan< 326,5 sebagai mutasi BRAF V600E negatif. Terdapat 17 (34%) kasus positifmengalami mutasi BRAF V600E. Rerata usia pada kasus dengan mutasi BRAF V600Epositif adalah 44,71 tahun. Ukuran tumor pada kasus dengan mutasi BRAF V600E positifberkisar antara 0,1-4cm. Tujuh belas kasus yang mengalami mutasi, 6 dlaki-laki dan 11perempuan. Tujuh kasus dengan perluasan keluar tiroid, 11 kasus dengan metastasiskelenjar getah bening (KGB), dan 8 kasus dengan varian histopatologik tall cell.Kesimpulan: Terdapat hubungan bermakna antara mutasi BRAF V600E denganperluasan keluar tiroid, metastasis kelenjar getah bening (KGB), dan varianhistopatologik tall cell. Tidak terdapat hubungan bermakna antara mutasi BRAFV600E dengan usia, jenis kelamin, dan ukuran tumor.

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ABSTRACTBackgroud: Papillary Thyroid Carcinoma (PTC) is the most common malignantneoplasm of the endocrine organ with an excellent prognosis, but in some casespresent with recurrency and mortality. There are prognostic factors and BRAFV600E mutation that related to worse prognosis. Immunohistochemicalinvestigetion of BRAF V600E protein believe can detect mutation wth 100%specificity and 89% sensitivity. Recent study suggest PTC with BRAF V600Emutation do thyroidectomy with prophylactic lymph node dissection. BRAFV600E specific inhibitor effective to the patient with advance stadium, patientwith metastases, and resistant to iodium radioactive. Aim of this study is to obtainBRAF V600E and the relation with prognostic factors.Material and Methods: This is a retrospective descriptive-analytic crosssectionalstudy. Fifty patient with PTC comes from Ciptomangunkusumo Hospitaland reviewed to determine prognostic factors microscopicaly. BRAF V600Emutation detected by immunohistochemical staining and assesed with H score.Result: H score ³ 326,5 determined as positive BRAF V600E mutation and <326,5 as negative BRAF V600E mutation. BRAF V600E mutation was detectedin 17 (34%) cases by immunohistochemistry. The mean age of the cases withpositive BRAF V600E mutation was 44.71 years, while the negative 41.58. Thesize of the tumor in cases with BRAF V600E mutation positive range between0,1-4cm, while negative 0,1-9cm. Seventeen cases have mutations, 6 of them sexmale and 11 female. Seven cases with extrathyroidal extension (ETE), 11 caseswith lymph node metastasis (KGB), and 8 cases with tall cell variant.Conclusion: There are significant correlation between BRAF V600E mutationwith extrathyroidal extension, lymph node metastases, and tall cell variant. Thereare no significant correlation between BRAF V600E mutation with age, gender,and size of the tumor, Backgroud: Papillary Thyroid Carcinoma (PTC) is the most common malignantneoplasm of the endocrine organ with an excellent prognosis, but in some casespresent with recurrency and mortality. There are prognostic factors and BRAFV600E mutation that related to worse prognosis. Immunohistochemicalinvestigetion of BRAF V600E protein believe can detect mutation wth 100%specificity and 89% sensitivity. Recent study suggest PTC with BRAF V600Emutation do thyroidectomy with prophylactic lymph node dissection. BRAFV600E specific inhibitor effective to the patient with advance stadium, patientwith metastases, and resistant to iodium radioactive. Aim of this study is to obtainBRAF V600E and the relation with prognostic factors.Material and Methods: This is a retrospective descriptive-analytic crosssectionalstudy. Fifty patient with PTC comes from Ciptomangunkusumo Hospitaland reviewed to determine prognostic factors microscopicaly. BRAF V600Emutation detected by immunohistochemical staining and assesed with H score.Result: H score ³ 326,5 determined as positive BRAF V600E mutation and <326,5 as negative BRAF V600E mutation. BRAF V600E mutation was detectedin 17 (34%) cases by immunohistochemistry. The mean age of the cases withpositive BRAF V600E mutation was 44.71 years, while the negative 41.58. Thesize of the tumor in cases with BRAF V600E mutation positive range between0,1-4cm, while negative 0,1-9cm. Seventeen cases have mutations, 6 of them sexmale and 11 female. Seven cases with extrathyroidal extension (ETE), 11 caseswith lymph node metastasis (KGB), and 8 cases with tall cell variant.Conclusion: There are significant correlation between BRAF V600E mutationwith extrathyroidal extension, lymph node metastases, and tall cell variant. Thereare no significant correlation between BRAF V600E mutation with age, gender,and size of the tumor]"

"PendahuluanMicroRNA (miR)-544a telah diidentifikasi sebagai pengatur potensial dalam jalur WNT/β-Catenin, namun perannya yang spesifik pada kanker paru-paru non-sel kecil (KPKBSK) dan hubungannya dengan resistensi kemoterapi berbasis platinum masih belum jelas. Oleh karena itu, kami bertujuan untuk menentukan hubungan antara ekspresi miR-544a dan GSK-3β, β-catenin, dan CD44 dengan resistensi kemoterapi berbasis platinum pada pasien KPKBSK stadium lanjut.MetodePenelitian ini dirancang sebagai studi kasus kontrol di mana individu yang didiagnosis dengan KPKBSK stadium lanjut (III-IV) dari Januari 2018 hingga Juli 2023 dari 6 rumah sakit berbeda di Indonesia. Analisis tingkat miR-544a dilakukan menggunakan Kit PCR QuantiTect SYBR Green secara real-time. Ekspresi GSK, β-catenin, dan CD44 menggunakan pewarnaan imunohistokimia (IHK) dilakukan dari formalin-fixed paraffin embedded (FFPE). Evaluasi intensitas IHK dibagi menjadi empat kategori ekspresi: negatif atau tidak berwarna, positif lemah, positif sedang, dan positif kuat. Dari 500 sel, kami menggunakan rumus semi-kuantitatif H-score.HasilStudi ini melibatkan 62 pasien KPKBSK stadium lanjut yang menjalani kemoterapi berbasis platinum dan menemukan miR-544a lebih tinggi pada responden yang buruk, dengan nilai p yang signifikan sebesar 0,009. Model prediktif untuk miR-544a menunjukkan nilai Roctab sebesar 0,6957. Nilai batas miR-544a sebesar 2,08 menghasilkan sensitivitas 64% dan spesifisitas 67,57%. Tingkat miR-544a di atas 2,08 secara signifikan terkait dengan respons pengobatan yang lebih buruk (OR 2,159, 95% CI 1,132 - 4,117, p = 0,016).KesimpulanStudi ini menunjukkan bahwa tingkat miR-544a merupakan biomarker yang signifikan untuk memprediksi respons kemoterapi pada pasien dengan KPKBSK stadium lanjut.......IntroductionMicroRNAs (miR)-544a has been identified as a potential regulator in the Wnt/β-Catenin pathway, but its specific role in non-small cell lung cancer (NSCLC) and its relationship with platinum-based chemotherapy resistance, remains unclear. Thus, we aim to determine the relationship between the expression of miR-544a and GSK-3β, β-catenin, and CD44 with platinum-based chemotherapy resistance in advanced stage NSCLC patients.MethodsThe research is designed as a case control study in which individuals diagnosed with advanced stage (III-IV) NSCLC from January 2018 and July 2023 from 6 different hospitals in Indonesia.The analysis of miR-544a levels was done using the real-time QuantiTect SYBR Green PCR Master Kit. The expression of GSK, β-catenin, and CD44 expression using immunohistochemistry (IHC) staining was performed from the formalin-fixed paraffin embedded (FFPE). The evaluation of IHC intensity was divided into four expression categories: negative or unstained, weakly positive, moderately positive, and strongly positive. From 500 cells, we used the semi-quantitative H-score formula.ResultsThis study of 62 advance NSCLC patients undergoing platinum-based chemotherapy and found miR-544a were higher in poor responders, with a significant p-value of 0.009. The predictive model for MiR-544a demonstrated a Roctab value of 0.6957. A miR-544a cutoff value of 2.08 yielded sensitivity of 64% and specificity of 67.57%. MiR-544a levels above 2.08 were significantly associated with poorer treatment response (OR 2.159, 95% CI 1.132 - 4.117, p = 0.016).ConclusionsThe study demonstrates that miR-544a levels are a significant biomarker for predicting chemotherapy response in patients with advance NSCLC."