HUBUNGAN EKSPRESI mRNA NGF - TRKA PADA KARSINOMA OVARIUM TIPE MUSINOSUM DAN SEROSUM DENGAN USIA SERTA UKURAN TUMOR

WORO DWI ASTUTI, dr. Dewiyani Indah Widyasari, Sp.PA., Ph.D.; dr. Totok Utoro, D.Med.Sc., Sp.PA(K).

2018 | Tesis-Spesialis | SP ILMU PATOLOGI ANATOMI

Latar Belakang Kanker ovarium merupakan masalah yang penting di bidang ginekologi karena insiden dan prevalensinya yang tinggi, diagnosis yang umumnya ditegakkan pada stadium lanjut, serta prognosisnya yang buruk dengan angka kematian yang tinggi. Nerve growth factor (NGF) dan reseptornya Tropomyosin-related kinases A (TRKA) diduga sebagai faktor angiogenik langsung dan tidak langsung yang berperan penting dalam karsinogenesis kanker ovarium. Penelitian ini bertujuan untuk mengetahui peningkatan ekspresi mRNA NGF dan TRKA pada karsinoma serosum dan musinosum dan korelasinya dengan usia dan ukuran tumor. Bahan dan Metode Penelitian ini merupakan penelitian observasional analitik menggunakan sampel berupa 80 blok parafin jaringan ovarium yang didiagnosis sebagai karsinoma serosum, karsinoma musinosum serta ovarium normal sebagai kontrol, yang diperoleh dari Departemen Patologi Anatomi Rumah Sakit DR.Sardjito dan laboratorium CITO Yogyakarta.Ekspresi mRNA NGF dan TRKA untuk masing-masing sampel dinilai menggunakan Real Time PCR.Perbedaan rerata ekspresi mRNA NGF dan TRKA serta korelasinya dengan usia dan ukuran tumor dianalisis dengan uji statistik dengan p<0,05 dianggap signifikan. Hasil dan Pembahasan Tidak terdapat peningkatan ekspresi mRNA NGF yang signifikan antara karsinoma serosum dan karsinoma musinosum dibandingkan dengan ovarium normal (p>0,05), namun terdapat peningkatan ekspresi mRNA NGF yang signifikan antara karsinoma serosum dibandingkan dengan karsinoma musinosum (p<0,05).Terdapat peningkatan ekspresi mRNA TRKA secara signifikan antara karsinoma serosum dan karsinoma musinosum dibandingkan dengan ovarium normal (p<0,05), namun tidak terdapat peningkatan ekspresi mRNA TRKA yang signifikan antara karsinoma serosum dibandingkan dengan karsinoma musinosum (p>0,05).Tidak terdapat peningkatan ekspresi mRNA NGF yang signifikan antara tumor tipe 1 dibandingkan dengan ovarium normal (p>0,05), namun terdapat peningkatan ekspresi mRNA NGF yang signifikan antara tumor tipe 2 dibandingkan dengan ovarium normal (p<0,05),terdapat peningkatan ekspresi mRNA NGF yang signifikan antara tumor tipe 2 dibandingkan dengan tumor tipe 1 (p<0,05).Terdapat peningkatan ekspresi mRNA TRKA yang signifikan antara tumor tipe 1 dan tumor tipe 2 dibandingkan dengan ovarium normal (p<0,05), terdapat peningkatan ekspresi mRNA TRKA yang signifikan antara tumor tipe 2 dibandingkan dengan tumor tipe 1 (p<0,05).Terdapat korelasi negatif dengan kekuatan korelasi lemah, yang signifikan, antara ekspresi mRNA NGF dengan usia pasien (rs= -0.360, p<0,05). Terdapat korelasi negatif dengan kekuatan korelasi lemah, yang signifikan antara ekspresi mRNA TRKA dengan usia (rs= -0.388, p<0,05). Terdapat korelasi positif dengan kekuatan korelasi lemah, yang tidak signifikan, antara ekspresi mRNA NGF dengan ukuran tumor (rs= 0,019, p>0,05).Terdapat korelasi positif dengan kekuatan korelasi sedang, yang signifikan, antara ekspresi mRNA TRKA dengan ukuran tumor (rs= 0.470, p<0,05). Kesimpulan: Ekspresi mRNA TRKA meningkat pada karsinoma serosum dan musinosum serta pada tumor tipe 1 dan tipe 2 selain itu, mempunyai korelasi sedang dengan ukuran tumor, sehingga diduga mempunyai peranan yang penting pada karsinogenesis kanker epithelial ovarium.

Background Ovarian cancer is an important issue in the field of gynecology due to its high incidence and prevalence, a diagnosis that is generally established at an advanced stage, as well as a poor prognosis with high mortality. Nerve growth factor (NGF) and its receptor Tropomyosin-related kinases A (TRKA) are thought to be direct and indirect angiogenic factors that play an important role in carcinogenesis of ovarian cancer. This study aims to investigate the increased expression of NGF and TRKA mRNA in serous and musinous carcinoma and its correlation with age and tumor size. Materials and Methods This study was an observational analytic study using a sample of 80 paraffin blocks of ovarian tissue diagnosed as serous carcinoma, musinous carcinoma and normal ovaries as control, obtained from the Department of Anatomical Pathology of DR.Sardjito Hospital and CITO Yogyakarta laboratory. NGF and TRKA mRNA expression for each sample was assessed using Real Time PCR. The difference in mean expression of NGF and TRKA mRNA as well as its correlation with tumor age and size was analyzed by statistical test with p <0.05 considered significant. Results and Discussion There was no significant increase in NGF mRNA expression between serous carcinoma and mucinous carcinoma compared with normal ovaries (p> 0.05), but there was a significant increase in NGF mRNA expression between serous carcinomas compared with the mucinous carcinoma (p <0.05). There was a significant increase in TRKA mRNA expression between serous carcinoma and mucinous carcinoma compared with normal ovaries (p <0.05), but no significant increase in TRKA mRNA expression between serous carcinomas compared with a mucinous carcinoma (p> 0.05). There was no significant increase in NGF mRNA expression between type 1 tumors compared with normal ovaries (p> 0.05), but there was a significant increase in NGF mRNA expression between type 2 tumors compared with normal ovaries (p <0.05), an increase significant NGF mRNA expression between tumor type 2 compared with tumor type 1 (p <0.05). There was a significant increase in TRKA mRNA expression between tumor type 1 and tumor type 2 compared with normal ovaries (p <0.05), there was a significant increase in TRKA mRNA expression between type 2 tumors compared with tumor type 1 (p <0.05) . There was a negative correlation with a significantly weak correlation strength, between expression of NGF mRNA and patient age (rs = -0.360, p <0.05). There was a negative correlation with a weak correlation strength, which was significant between TRKA mRNA expression and age (rs = -0.388, p <0.05). There was a positive correlation with a weak, insignificant correlation strength between NGF mRNA expression and tumor size (rs = 0.019, p> 0.05). There was a positive correlation with moderate correlation strength, significant between TRKA mRNA expression and tumor size ( rs = 0.470, p <0.05). Conclusion: TRKA mRNA expression is elevated in serous and mucinous carcinomas as well as in type 1 and type 2 tumors other than that, it has moderate correlation with tumor size, which is thought to have an important role in carcinogenesis of ovarian epithelial cancer.

Kata Kunci : NGF, TRKA, Karsinoma Serosum, Karsinoma Musinosum, Serous carcinoma, Mucinous carcinoma