BRCA1 expression, its correlation with clinicopathological features, and response to neoadjuvant chemotherapy in high-grade serous ovarian cancer.

Autor: Patil A; Department of Histopathology, Kidwai Memorial Institute of Oncology, Bangalore, India., Patil S; Division of Molecular Medicine, St. John's Research Institute, St John's Medical College, Bangalore, India., Anupama CE; Division of Molecular Medicine, St. John's Research Institute, St John's Medical College, Bangalore, India., Rajarajan S; Division of Molecular Medicine, St. John's Research Institute, St John's Medical College, Bangalore, India., Nimbalkar VP; Division of Molecular Medicine, St. John's Research Institute, St John's Medical College, Bangalore, India., Amirtham U; Department of Histopathology, Kidwai Memorial Institute of Oncology, Bangalore, India., Champaka G; Department of Histopathology, Kidwai Memorial Institute of Oncology, Bangalore, India., Suma MN; Department of Histopathology, Kidwai Memorial Institute of Oncology, Bangalore, India., Patil GV; Department of Histopathology, Kidwai Memorial Institute of Oncology, Bangalore, India., Nargund A; Department of Histopathology, Kidwai Memorial Institute of Oncology, Bangalore, India., Pallavi VR; Department of Gynecological Oncology, Kidwai Memorial Institute of Oncology, Bangalore, India., Jacob L; Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, India., Premalatha CS; Department of Histopathology, Kidwai Memorial Institute of Oncology, Bangalore, India., Prabhu JS; Division of Molecular Medicine, St. John's Research Institute, St John's Medical College, Bangalore, India.
Jazyk: angličtina
Zdroj: The journal of obstetrics and gynaecology research [J Obstet Gynaecol Res] 2023 Dec; Vol. 49 (12), pp. 2875-2882. Date of Electronic Publication: 2023 Sep 22.
DOI: 10.1111/jog.15796
Abstrakt: Aim: In high-grade serous ovarian cancers (HG-SOC), BRCA1 mutation is one of the predominant mutations reported by various studies. However, the non-mutational mechanisms of BRCA pathway inactivation in HG-SOC are unclear. We evaluated BRCA1 inactivation by estimating its expression with its repressor, ID4, in primary and neoadjuvant chemotherapy (NACT)-treated HG-SOC tumors with known therapeutic responses.
Methods: We evaluated the expression pattern of BRCA1 protein by immunohistochemistry in 119 cases of HG-SOC from a hospital cohort consisting of primary (N = 69) and NACT-treated (N = 50) tumors. Histological patterns (SET), stromal infiltration by lymphocytes (sTILs), and chemotherapy response score (CRS) were estimated by microscopic examination. Gene expression levels of BRCA1, and its repressor ID4, were estimated by qPCR. The association of BRCA1 protein and mRNA with clinicopathological features was studied. The relevance of the BRCA1/ID4 ratio was evaluated in tumors with different CRS.
Results: BRCA1 protein expression was observed in 12% of primary and 19% of NACT-treated HG-SOC tumors. We observed moderate concordance between BRCA1 protein and mRNA expression (AUC = 0.677). High BRCA1 mRNA expression was significantly associated with a more frequent SET pattern (p = 0.024), higher sTILs density (p = 0.042), and increased mitosis (p = 0.028). BRCA1-negative tumors showed higher expression of ID4 though not statistically significant. A higher BRCA1/ID4 ratio was associated with high sTILs density in primary (p = 0.042) and NACT-treated tumors (p = 0.040).
Conclusion: Our findings show the utility of the BRCA1/ID4 ratio in predicting neoadjuvant therapy response, which needs further evaluation in larger cohorts with long-term outcomes.
(© 2023 Japan Society of Obstetrics and Gynecology.)
Databáze: MEDLINE
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