High-grade ovarian serous carcinomas: Significant correlation of histologic patterns with IMP3 and E-Cadherin predicting disease recurrence and survival

Abstract

Most high-grade serous carcinomas (HGSC) of the ovary are advanced stage tumors with early recurrences. However, some tumors do not recur and have a better survival. We identified such cases of HGSC and compared those with the cases that recurred and assessed the relationship between patterns of invasion (intracystic, IC; micropapillary, MP; nonpapillary, NP) with IMP3 and E-Cadherin expression, and evaluated their predictive role in recurrence and survival. The study comprised of seventeen tumors recurred within 18 months of follow-up and 14 cases that did not recur with a minimum follow-up of 49 months. 73% tumors with predominantly MP pattern recurred, while only 27% of non-recurrent tumors showed this pattern. In contrast, predominant NP and IC patterns were seen in 71% of the non-recurrent and in 35% of recurrent tumors. 67.7% tumors expressed IMP3 and all cases expressed E-Cadherin. The tumors with a higher percentage of destructive invasion showed higher IMP3 positivity and greater chances of recurrence, whereas tumors with higher percentage of pushing invasion showed lower IMP3 positivity and lesser chances of recurrence (p = 0.02). IMP3-negative tumors had lower odds of recurrence than IMP3-positive ones (p = 0.01). The patients with negative IMP3 staining had a significantly higher OS than those with IMP3 positive tumors (p = 0.01), regardless of the histologic patterns. Also, reduction in E-Cadherin staining in the metastatic site led to poor DFS (p = 0.016) and OS (p = 0.006). IMP3 may serve as a useful prognostic marker that can stratify patients of advanced stage, high-grade serous carcinomas into two distinct subsets: majority with early recurrence with an infiltrative pattern of invasion and IMP3 positivity particularly in the MP areas; and a smaller subset that do not show early recurrence having pushing borders and are IMP3 negative. Also, E-Cadherin showed significant decrease in expression in the metastatic site of the recurrent cases.