The objective of this study was to evaluate the status of MYC and PVT1, which are frequently amplified in malignant tumors, and to assess their biological features according to histological subtypes in early-stage epithelial ovarian cancer (EOC).
Formalin-fixed and paraffin-embedded (FFPE) samples of 64 EOC tissues in International Federation of Gynecology and Obstetrics stages I-II and 20 normal ovarian tissues were analyzed for copy number and mRNA expression of MYC and PVT1 by qPCR and for MYC protein expression by immunohistochemistry. MYC protein expression was assessed by western blotting in a PVT1 siRNA-transfected ovarian cancer cell line. MYC and PVT1 was assessed as a prognostic factor using Kaplan-Meier analysis. The median follow-up period was 49.9 months and 17 cases in 64 of EOC recurred during follow-up.
Copy number variations showed significantly higher MYC and PVT1 in EOC than in normal ovaries. The copy number of PVT1 was significantly higher in serous carcinoma than in the other histological types. The mRNA of MYC and PVT1 was also higher in cancer tissues and showed a strong correlation in all histological subtypes. Immunohistochemistry revealed a positive association between the phosphorylated MYC (pMYC) index and high expression of proliferation markers, such as Ki-67 index, and a negative correlation between pMYC protein and the PVT1 copy number. Knockdown of PVT1 in ovarian cancer cell lines resulted in upregulation of MYC protein and pMYC. Kaplan-Meier survival analysis showed that low copy numbers of both MYC and PVT1 were associated with a statistically significantly poor prognosis.
Expression of pMYC and the Ki-67 index were affected by the PVT1 copy number but not mRNA. A high PVT1 copy number in FFPE samples might suggest favorable prognosis in early ovarian cancers.
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