Tesis

Analisis Ekspresi Protein HGF dan c-MET terhadap Proliferasi Sel pada Derajat Keganasan Karsinoma Ovarium = Expression analysis of HGF and C-MET toward cell proliferation in the degree of malignancy in ovarian carcinoma.

Kanker ovarium dikenal memiliki angka rekurensi dan mortalitas tinggi. Penentuan protein biomarker pada patogenesis kanker ovarium penting untuk menekan mortalitas. Salah satu protein yang berperan sebagai protoonkogen adalah protein hepatocyte growth factor (HGF) dan reseptor mesenchymal epithelial transition (c-MET). Interaksi antara HGF dan c-MET menyebabkan c-MET terfosforilasi dan memulai kaskade persinyalan berperan dalam proliferasi sel yang berdampak pada kecepatan mitosis dan derajat keganasan. Tujuan penelitian ini adalah menentukan tingkat ekspresi protein HGF dan c-MET pada proliferasi sel terinduksi dan derajat keganasan karsinoma ovarium. Penelitian ini merupakan penelitian potong lintang menggunakan 32 sampel jaringan karsinoma ovarium dalam bentuk blok parafin dikumpulkan dari Biobank IMERI FK UI. Setelah dilakukan analisis histopatologi, kemudian dilakukan pemeriksaan HGF, c-MET, dan Ki-67 dengan pulasan imunohistokimia, menggunakan antibodi primer anti-HGF polyclonal antibody, anti-c-MET monoclonal antibody, dan anti-Ki67 monoclonal antibody. Interpretasi pulasan menggunakan Histo-score (H score) yaitu menilai persentase sel dan intensitas sel yang terpulas. Hasil rerata pulasan menunjukkan terdapat perbedaan ekspresi HGF, c-MET dan Ki-67 (p = 0.04; 0.02; 0.04), di dapatkan korelasi positif antara ekspresi HGF dan Ki-67 dan derajat keganasan karsinoma ovarium (p = 0.001; r = 0.55). Dapat disimpulkan bahwa ekspresi HGF, c-MET dan Ki-67 meningkat pada karsinoma ovarium.
Kata kunci: HGF, c-MET, proliferasi sel, karsinoma ovarium


Ovarian cancer is known to have high recurrence and mortality rates. Determining protein biomarkers in the pathogenesis of ovarian cancer is important for reducing mortality. One of the proteins that acts as a proto-oncogene is hepatocyte growth factor (HGF) and the mesenchymal epithelial transition receptor (c-MET). The interaction between HGF and c-MET leads to c-MET phosphorylation and initiates signaling cascades involved in cell proliferation, which impacts the rate of mitosis and degree of malignancy. The objective of this study was to determine the expression levels of HGF and c-MET proteins in induced cell proliferation and the degree of malignancy in epithelial ovarian cancer. This study was cross-sectional research using 32 ovarian carcinoma tissue samples in the form of paraffin blocks collected from the IMERI Biobank, Faculty of Medicine, Universitas Indonesia. After histopathological analysis, HGF, c-MET, and Ki-67 were examined through immunohistochemical staining using primary antibodies, including anti-HGF polyclonal antibody, anti-c-MET monoclonal antibody, and anti-Ki-67 monoclonal antibody. The staining interpretation utilized the Histo-score (H-score), which assessed the percentage and intensity of stained cells. The mean staining results showed differences in HGF, c-MET and Ki-67 expression (p = 0.04; 0.02; 0.04), and a positive correlation was found between HGF and Ki-67 expression and the degree of malignancy in epithelial ovarian cancer (p = 0.01; r = 0.55). In conclusion, HGF, c-MET and Ki-67 expression are increased in epithelial ovarian cancer.
Keywords: HGF, c-MET, cell proliferation, ovarian carcinoma