Clinical factors and biomarker profiles associated with patient outcome in endometrioid ovarian carcinoma - Emphasis on tumor grade

Piret Soovares,Annukka Pasanen,Jonna Similä-Maarala,Ralf Bützow,Heini Lassus

doi:10.1016/j.ygyno.2021.10.078

Piret Soovares, Annukka Pasanen + Show 3 more

Open Access

https://doi.org/10.1016/j.ygyno.2021.10.078

Copy DOI

Journal: Gynecologic oncology	Publication Date: Oct 25, 2021
Citations: 7	License type: cc-by

Affiliation: University of Helsinki

Abstract

ObjectiveThe role of clinicopathological factors and molecular markers in prognostic classification of endometrioid ovarian carcinoma (EnOC) is not established. Tumor grade is used in risk assessment, but the role of current 3-tier grading system has been challenged. MethodsClinicopathological factors and 12 immunohistochemical biomarkers (PR, ER, β-catenin, vimentin, ARID1A, HNF1-β, p53, p16, MIB-1, E-cadherin, c-erb-B2 and L1CAM) were analyzed as regards patient outcome in 215 contemporarily classified EnOCs. ResultsOf clinical parameters, grade and stage appeared as strong independent prognostic factors both for disease-free and disease-specific overall survival. Grades 1–3 distinguished clearly from each other in the survival analysis, whereas stages I-II and stages III-IV clustered with each other. PR, ER, nuclear β-catenin and vimentin positivity were associated with favorable overall outcome and clinical parameters, whereas abnormal expression of p53, overexpression of p16 and L1CAM positivity were associated with aggressive disease characteristics and poor survival. The frequency of good-prognosis markers PR and β-catenin gradually decreased and poor-prognosis markers p53, p16 and L1CAM gradually increased from grade 1–3. However, vimentin and ER were expressed at similar frequencies across different grades and presented with independent prognostic significance. ConclusionsWe found histological grade and disease stage, but not residual tumor, to be independent clinical prognostic factors in EnOC. A set of good-prognosis markers (PR, ER, β-catenin and vimentin) and poor-prognosis markers (p53, p16 and L1CAM) were identified. Our findings support continuation of the use of the 3-tier grading system for EnOC and provide clinically feasible IHC biomarkers for prognostic profiling.

Highlights

Ovarian carcinomas are divided by morphology into five main types: high-grade serous, endometrioid, clear cell, mucinous, and low-grade serous carcinomas, which differ in clinical behavior and prognosis [1,2,3]
Grade and stage appeared as strong independent prognostic factors both for disease-free and disease-specific overall survival
PR, ER, nuclear β-catenin and vimentin positivity were associated with favorable overall outcome and clinical parameters, whereas abnormal expression of p53, overexpression of p16 and L1CAM positivity were associated with aggressive disease characteristics and poor survival

Summary

Introduction

Ovarian carcinomas are divided by morphology into five main types: high-grade serous, endometrioid, clear cell, mucinous, and low-grade serous carcinomas, which differ in clinical behavior and prognosis [1,2,3]. Endometrioid type is the second most common ovarian malignancy accounting for 10–15% of ovarian carcinomas. The prognosis of endometrioid ovarian carcinoma (EnOC) is good. In a significant proportion this is not the case reflecting heterogeneity of the molecular background of the disease [4,5]. Classification of ovarian cancers into clinically meaningful subgroups is needed to better understand the pathogenesis, estimate prognosis and tailor treatment in the era of targeted therapy

Methods

Results

Conclusion