Homologous Recombination Deficiency and Ovarian Cancer Treatment Decisions: Practical Implications for Pathologists for Tumor Typing and Reporting

Joseph T Rabban; Lee-May Chen; W Patrick Devine

doi:10.1016/j.path.2022.02.003

Homologous Recombination Deficiency and Ovarian Cancer Treatment Decisions: Practical Implications for Pathologists for Tumor Typing and Reporting

Surg Pathol Clin. 2022 Jun;15(2):219-234. doi: 10.1016/j.path.2022.02.003. Epub 2022 May 18.

Authors

Joseph T Rabban¹, Lee-May Chen², W Patrick Devine³

Affiliations

¹ Surgical Pathology Division, Pathology Department, University of California San Francisco, 1825 4th Street, M-2359, San Francisco, CA 94158, USA. Electronic address: joseph.rabban@ucsf.edu.
² Gynecologic Oncology Division, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA.
³ Molecular Pathology Division, Pathology Department, University of California San Francisco, San Francisco, CA, USA.

PMID: 35715159
DOI: 10.1016/j.path.2022.02.003

Abstract

Clinical testing for homologous repair (HR) deficiency (HRD) in ovarian cancers has emerged as a means to tailor the use of poly(ADP-ribose)polymerase (PARP) inhibitor therapy to the patients most likely to respond. The currently available HRD tests evaluate tumor tissue for genomic evidence of impairment of the HR pathway of DNA damage repair, which, if present, renders the tumor vulnerable to PARP inhibitors in conjunction with platinum chemotherapy. Germline or somatic mutation of BRCA1/2 is a major contributor HRD. Thus, tubo-ovarian/peritoneal high-grade serous carcinoma (HGSC) is enriched by HRD. After highlighting the general concepts underlying HRD testing and PARP inhibitor therapy, this review discusses practical roles for pathologists to maximize the opportunities for eligible patients with ovarian cancer to benefit from HRD testing, chiefly by applying contemporary diagnostic criteria for ovarian cancer tumor typing and navigating through potential pitfalls of tumor types that may mimic HGSC but are unlikely to harbor HRD.

Keywords: DNA repair; High-grade serous carcinoma; Homologous recombination deficiency; Ovarian cancer; PARP inhibitor.

Publication types

Review

MeSH terms

DNA Repair
Female
Homologous Recombination
Humans
Ovarian Neoplasms* / pathology
Pathologists*
Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use

Substances

Poly(ADP-ribose) Polymerase Inhibitors