BRCA1 expression, its correlation with clinicopathological features, and response to neoadjuvant chemotherapy in high-grade serous ovarian cancer.
BRCA1 dysfunction
HG-SOC
ID4
NACT response
Journal
The journal of obstetrics and gynaecology research
ISSN: 1447-0756
Titre abrégé: J Obstet Gynaecol Res
Pays: Australia
ID NLM: 9612761
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
28
04
2023
accepted:
10
09
2023
medline:
5
12
2023
pubmed:
22
9
2023
entrez:
22
9
2023
Statut:
ppublish
Résumé
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. 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. 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). 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.
Substances chimiques
BRCA1 Protein
0
RNA, Messenger
0
BRCA1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2875-2882Subventions
Organisme : Rajiv Gandhi University of Health Sciences (RGUHS)
ID : 18M014
Informations de copyright
© 2023 Japan Society of Obstetrics and Gynecology.
Références
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. GLobal Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249.
Sambasivan S. Epithelial ovarian cancer: review article. Cancer Treat Res Commun. 2022;33:100629. https://doi.org/10.1016/j.ctarc.2022.100629
Lisio MA, Fu L, Goyeneche A, Gao ZH, Telleria C. High-grade serous ovarian cancer: basic sciences, clinical and therapeutic standpoints. Int J Mol Sci. 2019;20(4):952.
Jessmon P, Boulanger T, Zhou W, Patwardhan P. Epidemiology and treatment patterns of epithelial ovarian cancer. Expert Rev Anticancer Ther. 2017;17(5):427-437. [cited 2023 Aug 9]. Available from: https://pubmed.ncbi.nlm.nih.gov/28277806/
Steinberga I, Jansson K, Sorbe B. Quality indicators and survival outcome in stage IIIB-IVB epithelial ovarian cancer treated at a single institution. In Vivo. 2019;33(5):1521-1530.
Žilovič D, Čiurlienė R, Sabaliauskaitė R, Jarmalaitė S. Future screening prospects for ovarian cancer. Cancers (Basel). 2021;13(15):3840.
Ngoi NYL, Tan DSP. The role of homologous recombination deficiency testing in ovarian cancer and its clinical implications: do we need it? ESMO Open. 2021;6(3):100144. https://doi.org/10.1016/j.esmoop.2021.100144
Liu Y, Lu LY. BRCA1 and homologous recombination: implications from mouse embryonic development. Cell Biosci. 2020;10(1):1-10. https://doi.org/10.1186/s13578-020-00412-4
da Cunha Colombo Bonadio RR, Fogace RN, Miranda VC, Diz MDPE. Homologous recombination deficiency in ovarian cancer: a review of its epidemiology and management. Clinics. 2018;73:1-6.
Konstantinopoulos PA, Spentzos D, Karlan BY, Taniguchi T, Fountzilas E, Francoeur N, et al. Gene expression profile of BRCAness that correlates with responsiveness to chemotherapy and with outcome in patients with epithelial ovarian cancer. J Clin Oncol. 2010;28(22):3555-3561.
Beger C, Pierce LN, Krüger M, Marcusson EG, Robbins JM, Welcsh P, et al. Identification of Id4 as a regulator of BRCA1 expression by using a ribozyme-library-based inverse genomics approach. Proc Natl Acad Sci U S A. 2001;98(1):130-135.
Glenn Mccluggage W, Judge MJ, Clarke BA, Davidson B, Gilks CB, Hollema H, et al. Data set for reporting of ovary, fallopian tube and primary peritoneal carcinoma: recommendations from the International Collaboration on Cancer Reporting (ICCR). Modern Pathology. 2015;28(8):1101-1122. https://doi.org/10.1038/modpathol.2015.77
Korlimarla A, Prabhu JS, Remacle J, Rajarajan S, Raja U, Anupama CE, et al. Identification of BRCA1 deficiency using multi-analyte estimation of BRCA1 and its repressors in FFPE tumor samples from patients with triple negative breast cancer. PloS One. 2016;11(4):e0153113.
Garg K, Levine DA, Olvera N, Dao F, Bisogna M, Secord AA, et al. BRCA1 immunohistochemistry in a molecularly characterised cohort of ovarian carcinomas. Am J Surg Pathol. 2013;37(1):138-146.
Bowtell DD, Wales NS, Böhm S, Hospital JR, Ox O. Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer. Nat Rev Cancer. 2016;15(11):668-679.
Bell D, Berchuck A, Birrer M, Chien J, Cramer DW, Dao F, et al. Integrated genomic analyses of ovarian carcinoma. Nature. 2011;474(7353):609-615.
Sun C, Li N, Yang Z, Zhou B, He Y, Weng D, et al. MiR-9 regulation of BRCA1 and ovarian cancer sensitivity to cisplatin and PARP inhibition. J Natl Cancer Inst. 2013;105(22):1750-1758.
Hollis RL, Churchman M, Michie CO, Rye T, Knight L, McCavigan A, et al. High EMSY expression defines a BRCA-like subgroup of high-grade serous ovarian carcinoma with prolonged survival and hypersensitivity to platinum. Cancer. 2019;125(16):2772-2781.
Soslow RA, Han G, Park KJ, Garg K, Olvera N, Spriggs DR, et al. Morphologic patterns associated with BRCA1 and BRCA2 genotype in ovarian carcinoma. Mod Pathol. 2012;25:625-636. Available from: www.modernpathology.org
Arakelyan A, Melkonyan A, Hakobyan S, Boyarskih U, Simonyan A, Nersisyan L, et al. Transcriptome patterns of BRCA1-and BRCA2-mutated breast and ovarian cancers. Int J Mol Sci. 2021;22(3):1-18.
Hwang WT, Adams SF, Tahirovic E, Hagemann IS, Coukos G. Prognostic significance of tumor-infiltrating T-cells in ovarian cancer: a meta-analysis. Gynecol Oncol. 2012;124(2):192-198.
Tumor O, Goode EL. Dose-response association of CD8+ tumor-infiltrating lymphocytes and survival time in high-grade serous ovarian cancer supplemental content. JAMA Oncol. 2017;3(12):173290 Available from: https://jamanetwork.com/
Hao J, Yu H, Zhang T, An R, Xue Y. Prognostic impact of tumor-infiltrating lymphocytes in high grade serous ovarian cancer: a systematic review and meta-analysis. Ther Adv Med Oncol. 2020;12:1-14.
Strickland KC, Howitt BE, Shukla SA, Rodig S, Ritterhouse LL, Liu JF, et al. Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer. Oncotarget. 2016;7(12):13587-13598. Available from: www.impactjournals.com/oncotarget/
Tsibulak I, Wieser V, Degasper C, Shivalingaiah G, Wenzel S, Sprung S, et al. BRCA1 and BRCA2 mRNA-expression prove to be of clinical impact in ovarian cancer. Br J Cancer. 2018;119(6):683-692. https://doi.org/10.1038/s41416-018-0217-4
Ledermann JA, Drew Y, Kristeleit RS. Homologous recombination deficiency and ovarian cancer. Eur J Cancer. 2016;60:49-58. https://doi.org/10.1016/j.ejca.2016.03.005