Ekspresi Protein B-RAF Mutan pada Karsinoma Tiroid Papilifer yang Bermetastasis ke Kelenjar Getah Bening Regional

Abstract

Abstrak

Karsinoma tiroid papilifer (KTP) dapat tumbuh progresif dan sekitar 33−61% kasus secara klinis telah metastasis ke kelenjar getah bening (KGB) regional pada saat diagnosis ditegakkan. Mutasi gen B-RAF dihubungkan dengan sifat biologis progresivitas KTP. Mutasi gen B-RAF akan mengkode protein B-RAF mutan yang bertindak sebagai regulator sentral pada jalur mytogen activated-pathway kinase (MAPK) dalam proses proliferasi dan dediferensiasi. Mutasi gen B-RAF dapat diidentifikasi pada tingkat deoxyribosenucleic acid (DNA), ribonucleic acid (RNA), dan protein. Masih terdapat kontroversi antara hubungan mutasi B-RAF dan metastasis KGB regional. Tujuan penelitian ini untuk mengetahui hubungan protein B-RAF mutan dengan metastasis ke KGB regional pada KTP. Penelitian ini merupakan penelitian observasional rancangan kuantitatif, studi kasus kontrol berpasangan. Penelitian dilakukan di Subbagian Bedah Onkologi, Kepala dan Leher, Departemen Ilmu Bedah dan Patologi Anatomi Fakultas Kedokteran Universitas Padjadjaran/ Rumah Sakit Dr. Hasan Sadikin Bandung. Sampel penelitian terdiri atas 38 kasus KTP dengan metastasis dan 38 kasus kontrol tanpa metastasis ke KGB regional yang dirawat di Rumah Sakit Dr. Hasan Sadikin Bandung pada periode Januari 2003−Desember 2010 dan dipilih berdasarkan proses matching. Masing-masing kelompok diperiksa B-RAF mutan dengan metode imunohistokimia. Hubungan antara tiap variabel bebas dan variabel tergantung diuji menggunakan analisis bivariat Uji McNemar.Hasil penelitian menunjukkan protein B-RAF mutan memiliki hubungan bermakna (p=0,023) dengan metastasis ke KGB regional pada KTP. Terdapat protein B-RAF mutan pada KTP mempunyai risiko untuk metastasis ke KGB regional sebesar 5,92 kali dibandingkan dengan tanpa mutasi B-RAF. Penelitian ini juga menunjukkan prevalensi B-RAF mutan sebesar 65,8% (32 kelompok kasus dan 18 kelompok kontrol). Simpulan, protein B-RAF mutan memiliki hubungan dengan metastasis ke KGB regional pada KTP. [MKB. 2013;45(4):245–50]

Kata kunci: Imunohistokimia, karsinoma tiroid papilifer, metastasis ke KGB regional, mutasi B-RAF

Mutant B-RAF Protein Expression in Regional Lymph Node Metastasized Papillary Thyroid Carcinoma

Papillary thyroid carcinoma (PTC) can become progressive and in about 33−61% of cases it has metastasized to regional lymph nodes at diagnosis. Mutation of B-RAF gene correlated with the biological characteristic of lymph node progressivity. Mutation of B-RAF will encode mutant B-RAF protein which acts as the central regulator on mytogen activated-pathway kinase (MAPK) pathway in terms of proliferation and dedifferentiation processes. B-RAF gene mutation can be identified at deoxyribosenucleic acid (DNA), ribonucleic acid (RNA) and protein levels. There are still controversies in corelation between B-RAF mutation and regional lymph node metastasis. The purpose of this study was to discover the correlation between mutant B-RAF protein and regional lymph node metastasis on PTC. This is a quantitative observational paired case-control study. The study was conducted at the Surgical Oncology, Head and Neck Division Departement of Surgery and Pathology Anatomy Departement, Faculty of Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin General Hospital Bandung in April 2011–January 2012. The sample consisted of 38 PTC cases with metastasis and 38 control cases without regional lymph node metastasis treated in Dr. Hasan Sadikin Hospital between January 2003–December 2010 which have been selected based on the matching process. Each group was examined using the immunohistochemistry method. Correlation between each dependent and non-dependent variables were tested using McNemar bivariate analysis. The results showed that mutant B-RAF protein have a significant correlation (p=0.023) with lymph node metastasis in PTC. The risk of metastasis in B-RAF mutant group was 5.92 times higher than without mutation. This study also showed that from 76 PTC cases studied, the prevalence of mutant B-RAF was about 65.8% (32 in cases and 18 in control group). In conclusion, there is a correlation between mutant B-RAF protein and regional lymph node metastasis in papillary thyroid carcinoma. [MKB. 2013;45(4):245–50]

Key words: B-RAF mutation, immunohystochemistry, papillary thyroid carcinoma, regional lymph node metastasis

DOI: http://dx.doi.org/10.15395/mkb.v45n4.200