This license enables reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator.
Shradha Sivadas, Tejas Vidwans, Vidya Chandraprabha et. al, Histopathologic Features of High grade Serous Ovarian Carcinomas associated with BRCA Mutation. Ind J Genet Mol Res. 2026; 15(1): 07-12.
Timeline
Received : December 13, 2025
Accepted : December 30, 2025
Published : June 30, 2026
Abstract
Background: High-grade serous ovarian carcinoma (HGSOC) is frequently associated with homologous recombination repair (HRR) deficiency due to BRCA1/2 mutations. Recognition of characteristic histopathological patterns in BRCA-mutated and HRD-positive tumours has diagnostic and therapeutic relevance. Objective: To identify distinctive histomorphological features associated with BRCA mutated and/or HRD-positive HGSOC and correlate them with clinicopathological parameters. Methods: A retrospective observational study was conducted. Of the 333 histologically confirmed HGSOC cases (2018–2024), 48 underwent BRCA testing, and 9 had concurrent HRD analysis. Archival haematoxylin and eosin (H&E) slides were reviewed for SET morphology (solid, pseudo-endometrioid, transitional), necrosis, nuclear pleomorphism, mitotic index, and tumour infiltrating lymphocytes (TILs). Clinical and molecular data were retrieved, and statistical associations were analysed using Chi-square and Fisher’s exact tests. Results: Among 48 tested cases, BRCA1 mutations were identified in 25% and BRCA2 in 2.1%; 33.3% (16/48) were BRCA / HRD positive. BRCA/HRD-positive tumours showed significantly higher frequencies of necrosis, high mitotic activity, lymphovascular invasion, and SET pattern. The odds of BRCA/HRD positivity were approximately 13–17 times higher in tumours exhibiting SET morphology. TILs were more frequent but not statistically significant.
References
1. Kurman RJ, Shih IM. The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am J Surg Pathol. 2010;34(3):433-43.
2. Norquist BM, et al. Inherited mutations in women with ovarian carcinoma. JAMA Oncol. 2016;2(4):482-90.
3. Mavaddat N, et al. Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis. J Natl Cancer Inst. 2013;105(11):812-22.
4. Norquist BM, Harrell MI, Brady MF, et al. Inherited mutations in women with ovarian carcinoma. JAMA Oncol. 2016;2(4):482–490.
5. International Agency for Research on Cancer. Global Cancer Observatory: Cancer Today. Lyon, France: IARC; 2020. Available from: https://gco.iarc.fr/today
6. Gupta N, Dey S. Histopathological Patterns of Ovarian Tumours in a Tertiary Care Hospital in Western India. J Obstet Gynaecol India. 2015;65(Suppl 1):42–46.
7. Kumar A, Bansal A, Sirohi B, et al. BRCA1 and BRCA2 germline mutation analysis and clinicopathological correlation in an Indian cohort of ovarian cancer patients. Cancer Genet. 2018;226–227:1–6.
8. Sudeep A, Nair SV, Raju K, et al. Clinicopathological profile of ovarian cancer patients in a tertiary care centre: A retrospective analysis. J Clin Sci Res. 2021; 10:49–54.
9. Khalique S, Naidoo K, Attygalle AD, et al. Optimised clinical and immunohistochemistry workflows for diagnosing high-grade serous carcinoma with SET morphology in BRCA mutation carriers. Histopathology. 2020;76(3):368–377
10. Norquist B, Wurz KA, Pennil CC, et al. Secondary somatic mutations restoring BRCA1/2 predict chemotherapy resistance in hereditary ovarian carcinomas. J Clin Oncol. 2011;29(22):3008–3015.
11. Paul DiSilvestro et al. Overall Survival With Maintenance Olaparib at a 7-Year Follow-Up in Patients With Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: The SOLO1/GOG 3004 Trial. J Clin Oncol 41, 609- 617(2023).
12. Soslow RA, Han G, Park KJ, et al. Morphologic patterns associated with BRCA1 and BRCA2 genotype in ovarian carcinoma. Mod Pathol. 2012;25(4):625–636.
13. Samuel D, Diaz-Barbe A, Pinto A, Schlumbrecht M, George S. Hereditary Ovarian Carcinoma: Cancer Pathogenesis Looking beyond BRCA1 and BRCA2. Cells. 2022; 11(3):539.
14. Alda Birgisdóttir, Tor Åge Myklebust, Merete Bjørnslett, Vibeke W. Rognlien, Torbjorn Paulsen, Anne Dørum,BRCA mutation testing and association with oncologic outcome and incidence of ovarian cancer in Norway,International Journal of Gynecological Cancer, Volume 35, Issue 2,2025,
15. Aköz G, Özer Kaya Ö, Özdemir T, Çakır İ, Kelten Talu C. The Histopathological Findings of High-grade Serous Ovarian Carcinomas in Patients with BRCA Germline Mutations, Single Center Experience. Anatol J Gen Med Res. ;34(1):50-56. 2023
16. X.H. Wu et al, Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial, Annals of Oncology, Volume 32, Issue 4, 2021, Pages 512-521.
17. Ray-Coquard I, Pautier P, Pignata S, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med. 2019;381(25):2416–2428.
18. Soslow RA, Han G, Park KJ, et al. Morphologic patterns associated with BRCA1 and BRCA2 genotype in ovarian carcinoma. Mod Pathol. 2012;25(4):625–636.
19. Krishnan R, Patel PS, Hakem R. BRCA1 and Metastasis: Outcome of Defective DNA Repair. Cancers (Basel). 2021 Dec 27;14(1):108.
20. Marcel A.T.M. van Vugt, Eileen E. Parkes,When breaks get hot: inflammatory signaling in BRCA1/2-mutant cancers,Trends in Cancer, Volume 8, Issue 3, 2022, Pages 174-189.
21. Coleman RL, Oza AM, Lorusso D, et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomized, doubleblind, placebo-controlled, phase 3 trial. Lancet. 2017;390(10106):1949–1961.
Data Sharing Statement
There are no additional data available. All raw data and code are available upon request.
Funding
This research received no funding.
Author Contributions
All authors contributed significantly to the work and approve its publication.
Ethics Declaration
This article does not involve any human or animal subjects, and therefore does not require ethics approval.
Acknowledgements
We would like to express our gratitude to the patients, their families, and all those who have contributed to this study.
Conflicts of Interest
The authors report no conflicts of interest in this work.
About this article
Cite this article
Shradha Sivadas, Tejas Vidwans, Vidya Chandraprabha et. al, Histopathologic Features of High grade Serous Ovarian Carcinomas associated with BRCA Mutation. Ind J Genet Mol Res. 2026; 15(1): 07-12.
This license enables reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator.
This license enables reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator.