EKSPRESI mRNA NOTCH-1 PADA KARSINOMA OVARIUM TIPE MUSINOSUM DAN SEROSUM HIGH-GRADE SERTA HUBUNGANNYA DENGAN USIA DAN UKURAN TUMOR

NURWESTRI H, dr. Didik Setyo Heriyanto, Sp.PA, Ph.D ; Dr. dr. Irianiwati, Sp.PA(K)

2018 | Tesis-Spesialis | SP ILMU PATOLOGI ANATOMI

Latar Belakang: Karsinoma ovarium dikelompokkan menjadi tipe I (low-grade) dan tipe II (highgrade). Salah satu jenis karsinoma tipe I yaitu karsinoma musinosum dan tipe II yaitu karsinoma serosum high-grade. Sinyal Notch dapat menjadi onkogen maupun tumor supressor tergantung jenis sel dan jaringan. Pada ovarium, Notch-1 berperan mendorong pertumbuhan sel kanker. Peningkatan ekspresi Notch-1 berhubungan dengan peningkatan derajat histopatologis, stadium, dan overall survival buruk. Namun demikian, peran Notch-1 pada karsinogenesis ovarium masih belum jelas. Penelitian ini bertujuan mengetahui ekspresi mRNA Notch-1 pada karsinoma musinosum dan serosum high-grade. Metode: Sampel berupa jaringan Formalin-Fixed Parrafin-Embedded (FFEP) dari karsinoma musinosum, serosum high-grade, dan ovarium normal masing-masing 25. Karsinoma dibagi kelompok usia <55 tahun dan 55 tahun, serta ukuran <=10 cm dan >10 cm. Ekspresi mRNA Notch-1 diperoleh dengan protokol Hybrid-Rtm dan One Step qRT-PCR kemudian hasil dianalisis dengan one-way ANNOVA, Ttest dan uji Spearman. Hasil: Dari 75 sampel didapatkan ekspresi mRNA Notch-1 pada ovarium normal, karsinoma musinosum, dan serosum high-grade yaitu 3,49, 8,29, dan 9,38. Ada perbedaan bermakna ekspresi mRNA Notch-1 antara karsinoma dengan ovarium normal (p<0,0001), namun antara karsinoma musinosum dengan serosum highgrade tidak berbeda bermakna (p=0,475).Tidak ada perbedaan bermakna ekspresi mRNANotch-1 pada karsinoma musinosum dan serosum high grade antara kelompok usia <55 dan 55 tahun (p=0,659 dan p=0,058), serta ukuran <=10 dan >10 cm (p=0,763 dan p=0,120). Ekspresi mRNA Notch-1 pada karsinoma musinosum dan serosum high-grade tidak berhubungan bermakna dengan usia (p=0,074 dan p=0,166) dan ukuran tumor (p=0,270 dan p=0,152). Kesimpulan: Ekspresi mRNA Notch-1 meningkat pada karsinoma ovarium, namun tidak berbeda bermakna antara karsinoma musinosum dengan serosum high-grade pada semua kelompok usia dan ukuran tumor serta tidak berhubungan bermakna dengan usia dan ukuran tumor.

Background: Ovarian surface epithelial tumor (carcinoma) is classified into low grade (type I) and high grade (type II). Mucinous carcinoma is included in type I while highgrade serous carcinoma is in type II. Notch signals can be either oncogene or tumor suppressor depends on cell type and cellular context. In the ovary, Notch-1 contributes to the cancer cells growth. Overexpression of Notch-1 is associated with poor grade, higher stadium, and worse overall survival. However, the role of Notch-1 in ovarian carcinogenesis remains unclear and needs further studies. The aim of this study is to investigate the difference between mRNA Notch-1 expression in mucinous and high-grade serous carcinomas. Methods: Samples were taken from Formalin-Fixed Parrafin-Embeded (FFPE) tissues; divided into 3 groups of cases which are musinous carcinomas, high grade serous carcinomas, and normal ovaries. Each group have 25 samples. Samples then divided by age group (<55 years and >=55 years), and size (<=10 cm and >10 cm). mRNA Notch-1 expression was obtained with Hybrid-Rtm protocol and One Step qRT-PCR procedure. The differences and correlations of mRNA Notch-1 expression were analyzed by one-way ANNOVA, T-test, and Spearman test. Results: From 75 samples, expression of mRNA Notch-1 in normal ovaries, musinous, and high-grade serous carcinomas were 3.49, 8.29 and 9.38. There was a significant difference between carcinomas and normal ovaries (p<0.0001), while musinous and high-grade serous carcinomas showed the opposite result (p=0,475). There was no significant difference of mRNA Notch-1 expression in mucinous and high-grade serous carcinomas between age group <55 and >=55 years (p=0,659 and p=0,058), and size <=0 and >10 cm (p=0,763 and p=0,120). mRNA Notch-1 expression in mucinous and high-grade serous carcinomas was no significant correlation with age (p=0,074 and p=0,166) and tumor size (p=0,270 and p=0,152). Conclusion: mRNA Notch-1 expression is elevated in ovarian carcinomas, but not significantly different between musinous and high-grade serous carcinomas, in all age groups and tumor sizes, also not significantly correlate with age and tumor size.

Kata Kunci : Karsinoma musinosum, serosum high-grade, mRNA Notch-1, usia, ukuran, Musinous carcinoma, high-grade serous, mRNA Notch-1, age, size