Molecular portraits of clear cell ovarian and endometrial carcinoma with comparison to clear cell renal cell carcinoma.

Abstract

OBJECTIVE:

Advanced clear cell gynecologic malignancies remain among the most challenging diseases to manage. We evaluated ovarian and endometrial clear cell carcinoma (OCCC and ECCC) specimens using comprehensive sequencing technology to identify mutational targets and compared their molecular profiles to histologically similar clear cell renal cell carcinoma (ccRCC).

METHODS:

Using next-generation sequencing (NGS), fragment analysis (FA), and in situ hybridization (ISH), 164 OCCC, 75 ECCC and 234 ccRCC specimens from 2015 to 2018 were evaluated and compared.

RESULTS:

The highest mutation rates in ECCC and OCCC were noted in: ARID1A (75.0%, 87.5%), TP53 (34.8%, 11.1%), PIK3CA (25.0%, 46.8%), PPP2R1A (8.7%, 16.7%), MSI-high (8.8%, 6.4%) and PTEN (8.3%, 7.1%). Among these mutations, there was no significant difference between OCCC and ECCC mutation prevalence except in TP53, with higher mutation rates in ECCC versus OCCC (34.8 vs. 11.1%, respectively, p < 0.05). ccRCC demonstrated different mutation profiles with higher mutation rates in VHL (80.3%), PBRM1 (43.9%), SETD2 (31.1%), and KDM5C (29.2%). By contrast, VHL, PBRM1, and SETD2 mutations were not found in ECCC and OCCC (0.0%). Compared to ccRCC and ECCC, OCCC was found to have a significantly higher tumor mutation burden (TMB) (19.1%).

CONCLUSION:

Gynecologic and renal CCC demonstrate separate and disparate somatic profiles. However, OCCC and ECCC are diseases with similar profiles. TMB and MSI analyses indicate that a subset of OCCC may benefit from immunotherapy. Prospective clinical trials are needed and are underway to examine targeted therapies in these gynecologic disease subtypes.

• Authors: Sarah A Ackroyd, David Arguello, Pilar Ramos, Haider Mahdi, Adam ElNaggar, Ira Winer, Rob Holloway, Thomas Krivak, Nathaniel Jones, Valerie Galvan Turner, Thomas Herzog, Christina Chu, Jubilee Brown, Gina Mantia-Smaldone
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 169 Pg. 164-171 (02 2023) ISSN: 1095-6859 [Electronic] United States
• PMID: 36333181 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Topics

• Humans
• Female
• Carcinoma, Renal Cell (genetics, pathology)
• Prospective Studies
• Endometrial Neoplasms (genetics)
• Mutation
• Kidney Neoplasms (genetics)
• Adenocarcinoma, Clear Cell (genetics, pathology)
• Ovarian Neoplasms (genetics, pathology)