BRCA1 promoter methylation & its immunohistochemical correlation in sporadic breast cancer

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dc.contributor.authorKhan, Fatimaen_US
dc.contributor.authorAgarwal, Preetien_US
dc.contributor.authorGupta, Sameeren_US
dc.contributor.authorMaurya, Malti Kumarien_US
dc.contributor.authorSingh, Poojaen_US
dc.contributor.authorAgarwal, Apoorvaen_US
dc.contributor.authorSingh, Kulranjanen_US
dc.contributor.authorSonkar, Abhinav, Arunen_US
dc.contributor.authorGoel, Madhu Matien_US
dc.date.accessioned2023-08-19T04:51:52Z
dc.date.available2023-08-19T04:51:52Z
dc.date.issued2023-01
dc.description.abstractBackground & objectives: Studies have shown that apart from hereditary breast carcinomas, breast cancer susceptibility gene 1 (BRCA1) mutations conferring to its loss are seen in sporadic breast carcinomas (SBC) as well. The aim of the present study was to assess BRCA1 methylation in females presenting at King George’s Medical University, Lucknow, with SBC by both immunohistochemistry (IHC) and methylation PCR with respect to hormonal profile and various morphological prognostic parameters. The primary objective was to look for the association between BRCA1 protein expression and DNA promoter methylation. Methods: 81 mastectomy specimens from SBC of invasive breast carcinoma (no special type) were included in this study. After a detailed morphological assessment, formalin fixed paraffin embedded tissue from a representative tumour area was selected for BRCA1 IHC by heat-mediated antigen retrieval under high pH and DNA extraction and further bisulphate treatment. BRCA1 was studied for methylation by methylated and unmethylated PCR-specific primers. Results: BRCA1 promoter methylation was present in 42/81 (51.9%) participants, with significant BRCA1 protein loss (72.7%; P=0.002). A significant association between BRCA1 loss and hormonal profile was found (P=0.001); maximum in triple negative breast carcinoma (TNBC) (72%; 18/25). Most of the TNBC also harboured methylation (68%). Although not significant grade II and III tumours, lymph vascular invasion, ductal carcinoma in situ, and nodal metastasis (?3) were seen in a higher percentage in methylated tumours. Mortality in SBC was significantly associated with BRCA1 loss (30.3%; P=0.024). Interpretation & conclusions: Study results highlight the concept of “BRCAness” in SBC as well. Hence, we can confer that identification of BRCA1 loss in SBC can make it a perfect candidate for poly ADP- ribose polymerase inhibitors or cisplatin-based therapy like hereditary ones.en_US
dc.identifier.affiliationsDepartments ofen_US
dc.identifier.affiliationsPathologyen_US
dc.identifier.affiliationsSurgical Oncologyen_US
dc.identifier.affiliationsGeneral Surgeryen_US
dc.identifier.affiliationsEndocrine Surgery, King George’s Medical University, Lucknow, Uttar Pradeshen_US
dc.identifier.affiliationsDepartment of Biotechnology, A.N. College, Magadh University, Bodh Gaya, Bihar, Indiaen_US
dc.identifier.citationKhan Fatima, Agarwal Preeti, Gupta Sameer, Maurya Malti Kumari, Singh Pooja, Agarwal Apoorva, Singh Kulranjan, Sonkar Abhinav Arun, Goel Madhu Mati. BRCA1 promoter methylation & its immunohistochemical correlation in sporadic breast cancer . Indian Journal of Medical Research. 2023 Jul; 158(1): 47-54en_US
dc.identifier.issn0971-5916
dc.identifier.placeIndiaen_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/223571
dc.languageenen_US
dc.publisherWolters Kluwer – Medknowen_US
dc.relation.issuenumber1en_US
dc.relation.volume158en_US
dc.source.urihttps://doi.org/10.4103/ijmr.IJMR_4605_20en_US
dc.subjectBRCA1en_US
dc.subjectBreast cancer susceptibility gene 1en_US
dc.subjectimmunohistochemistryen_US
dc.subjectpromoter methylationen_US
dc.subjectsporadic breast carcinomaen_US
dc.subjecttriple negative breast canceren_US
dc.titleBRCA1 promoter methylation & its immunohistochemical correlation in sporadic breast canceren_US
dc.typeJournal Articleen_US
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