Abstract

High-grade serous ovarian carcinoma (HGSC) is one of the major tumors of the gynecological system with a poor survival rate and variable microscopic appearance. It was suggested that SET (solid, pseudo-endometrioid and transitional-like) morphology in ovarian HGSC is predictably associated with BRCA deficiencies. In this study, we investigated the microscopic patterns and some immunohistochemical markers predicting the prognosis of serous carcinoma. We re-evaluated 305 HGSC ovarian resections morphologically and calculated the SET morphology percentages for each case. Morphological and immunohistochemical data correlated with the survival and post-treatment disease progression data. The median age at diagnosis was 57 years and the median follow-up period was 3.1 years. The median overall survival (OS) of ovarian carcinoma in SET-predominant tumors (n=60) was 81 months, while for tumors with SET non-dominant morphology (n=63) and non-SET morphology (n=182) it was 59.7 and 44.7 months, respectively. Predominant (more than 50%) SET morphology was significantly associated with increased survival rates of HGSC. Immunohistochemically, p53, ERCC1, ER, and PR antibodies were applied and only PR antibody positivity was found to be associated with borderline statistical significance for increased survival rates. Our results suggest that SET morphology may be a potential predictive and prognostic marker in managing the treatment strategies of HGSC.

Highlights

  • Ovarian cancer is associated with a high mortality rate among women [1]

  • By reviewing a relatively large set of high-grade serous carcinomas, diagnosed according to WHO 2020 criteria, we demonstrated that these tumors could be potentially heterogeneous by their genetic and IHC profile and by their morphological pattern and prognostic surveillance

  • In 2006, early tubal carcinomas were considered as precursors of high-grade serous carcinomas, and later in 2012, patients with BRCA mutations were found to have a different morphology such as SET compared to classical serous papillary carcinomas, and recently in 2015, lesser precursor lesions were reported in tumors with a BRCA mutation, leading to the opinion that serous carcinomas may reflect a more heterogeneous neoplastic development rather than a homogenous tumor group [6, 9, 10]

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Summary

INTRODUCTION

Ovarian cancer is associated with a high mortality rate among women [1]. More than 70% of ovarian cancers are diagnosed at an advanced stage and the absence of an accepted early diagnostic method is one of the main reasons for the increased mortality. Intraepithelial carcinomas are reported at a fallopian tube location in BRCA deficient patients and currently, it is widely accepted that the majority of high-grade serous carcinomas (HGSCs) are tubal in origin. The objective of this study was to investigate the effect of SET morphology on clinical outcome and expression of certain proteins such as p53, ER, PR, and ERCC1 in patients with tubo-ovarian high-grade serous carcinoma. After reviewing the selected cases according to the WHO 2020 criteria, 23 samples were found to have different morphologies than HGSC such as low-grade serous carcinoma, borderline serous tumors, etc. After excluding these cases, 305 ‘high-grade serous ovarian carcinoma’ cases were included in the study. Several 4-5 micrometer thick sections obtained from TMA blocks were stained with hematoxylin and eosin (H&E) and immunohistochemical staining was performed on the Leica BOND-MAX IHC/ISH automated immunostainer using the following commercial antibodies; ER (Biocare; EDTA 1/50; 6F11), PR (Biocare; EDTA 1/100; SP2), p53 (Biocare; EDTA 1/200; DO-7) and ERCC1 (Biocare; EDTA 1/100; 4F9)

Evaluation of Immunohistochemical Results
RESULTS
DISCUSSION
CONFLICT OF INTEREST

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