mmunohistochemical and molecular genetic profiling in determining pathogenetic variants of malignant epithelial ovarian tumors

Authors

  • I.R. Hrytsay Municipal Non-Profit Enterprise of the Lviv Regional Council “Lviv Oncological Regional Treatment and Diagnostic Center”; Danylo Halytsky Lviv National Medical University, Lviv, Ukraine https://orcid.org/0009-0007-0751-6981
  • O.A. Petronchak “Western Ukrainian Histological Laboratory”, Lviv, Ukraine https://orcid.org/0000-0001-7703-3036
  • N.A. Volodko Danylo Halytsky Lviv National Medical University; Municipal Non-Profit Enterprise of the Lviv Regional Council “Lviv Oncological Regional Treatment and Diagnostic Center”, Lviv, Ukraine https://orcid.org/0000-0002-4478-5554

DOI:

https://doi.org/10.18370/2309-4117.2025.79.65-76

Keywords:

ovarian cancer, histology, carcinoma, immunohistochemistry, biomarkers, pathomorphological types, gene mutations, molecular profiling

Abstract

Objective of the study: to investigate immunohistochemical and molecular markers in tumor samples representing different pathomorphological types of ovarian cancer (OC) and assess their predictive value.
Materials and methods. A retrospective analysis was conducted on 37 tumor samples obtained from patients with OC through primary cytoreductive surgery, diagnostic laparoscopy with biopsy, or trephine biopsy of distant metastases. The study utilized an immunohistochemical panel assessing the expression of WT-1, p53, Napsin A, and progesterone receptors, along with a molecular genetic panel targeting mutations in HRR, TP53, and other key genes.
Results. Histological analysis identified the following tumor distribution: high-grade serous carcinoma (HGSC) – 19 cases (51.4%), endometrioid carcinoma (ENOC) – 7 (18.9%), clear cell carcinoma (CCC) – 7 (18.9%), and unclassified tumors – 4 (10.8%).
The distribution was revised following immunohistochemical analysis: HGSC – 21 cases (56.8%), ENOC – 7 (18.9%), CCC – 6 (16.2%), and low-grade serous carcinoma (LGSC) – 3 (8.1%). A discrepancy between pathomorphological and immunohistochemical diagnoses was observed in 21.6% of cases; however, immunohistochemical technique enabled a definitive subtype diagnosis in 97.3% of cases.
Among 21 HGSC cases, TP53 mutations were detected in 11 (50%) patients, BRCA1 in 5 (22.7%), BRCA2 in 2 (9.1%), CDK12 in 2 (9.1%), and one case each of AR (4.5%) and PIK3CA (4.5%).
In ENOC cases, BRCA1 mutations were found in 2 (25.6%) patients, TP53 in 3 (42.9%), and one case each – RAD51C (14.7%) and KRAS (14.7%).
In CCC, molecular profiling revealed mutations in the following genes: TP53 –1 case (16.7%), NBN – 1 case (16.7%), RAD51C – 1 case (16.7%). Overall, TP53 mutations were identified in 11 (52.4%) cases using next-generation sequencing, while p53 protein abnormalities were observed in 14 (66.7%) cases via immunohistochemical analysis.
Conclusions. Immunohistochemistry is essential for the accurate classification of malignant epithelial ovarian tumors. Concurrently, molecular profiling provides critical insights into homologous recombination repair deficiencies and reveals key mutations not only in HGSC but also in ENOC and CCC subtypes. Together, these tests support personalized treatment selection, including tailored chemotherapy regimens and targeted therapies, potentially enhancing treatment response and patient outcomes.

Author Biographies

I.R. Hrytsay, Municipal Non-Profit Enterprise of the Lviv Regional Council “Lviv Oncological Regional Treatment and Diagnostic Center”; Danylo Halytsky Lviv National Medical University, Lviv

oncologist of chemotherapy;
postgraduate student of the Department of Oncology and Radiology

O.A. Petronchak, “Western Ukrainian Histological Laboratory”, Lviv

pathologist

N.A. Volodko, Danylo Halytsky Lviv National Medical University; Municipal Non-Profit Enterprise of the Lviv Regional Council “Lviv Oncological Regional Treatment and Diagnostic Center”, Lviv

MD, professor, head of the Department of Oncology and Radiology;
gynecological oncologist at the Gynecological Department No. 1

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Published

2025-09-18

How to Cite

Hrytsay, I., Petronchak, O., & Volodko, N. (2025). mmunohistochemical and molecular genetic profiling in determining pathogenetic variants of malignant epithelial ovarian tumors. REPRODUCTIVE ENDOCRINOLOGY, (79), 65–76. https://doi.org/10.18370/2309-4117.2025.79.65-76

Issue

No. 79 (2025)

Section

Tumors and pretumoral pathology

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