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Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 3 February 2013, last major update February 2013
Copyright: (c) 2002-2013, PathologyOutlines.com, Inc.


● Tumor suppressor gene at 13q12-13; considered a "caretaker" gene that maintains stability in the cellular network, rather than a "gatekeeper" gene that directly inhibits cell growth or promotes cell death (OMIM 600185)
● Interacts with RAD51; may facilitate homologous recombination in bypass of stalled replication forks
● Loss of functional BRCA1 or BRCA2 leads to activation of p53, causing cell cycle arrest or apoptosis
● If p53 if inactivated, proliferation results in progressive accumulation of DNA damage and increased frequency of malignancy
● 6174delT in BRCA2 common in Ashkenazi Jews
● BRCA1 and BRCA2 mutations in Ashkenazi Jews have 2% prevalence vs. 0.1% of rest of population
● Gene first cloned at Myriad Genetics, and the subject of extensive patent litigation (Wikipedia)

● See also BRCA2 associated breast carcinoma
● Patients with BRCA1 or BRCA2 mutation have a 35%-80% lifetime risk of breast cancer by age 70; usually high grade, aneuploid, but ER+, PR+ (Mod Pathol 2005;18:1305)
● Higher risk with 4486 G > T mutation
● Men with BRCA2 mutation have higher risk of breast cancer also

● 15%-27% lifetime risk of adenocarcinoma in women with mutations
● Often younger patients with high stage tumors
● BRCA mutations cause 90% of hereditary cases of ovarian carcinomas, which account for 10% of all ovarian carcinomas (Hum Pathol 2005;36:861)
● For patients with known BRCA1 or BRCA2 mutation or family history of breast or ovarian cancer, should submit entire fallopian tube and ovary for microscopic examination Am J Surg Pathol 2002;26:171, Am J Surg Pathol 2001;25:1283), as incidental neoplasms are common (Am J Surg Pathol 2006;30:1222)

● Also causes familial cancers of pancreas (Arch Pathol Lab Med 2009;133:365) and prostate; associated with esophageal squamous cell carcinoma in China (Asian Pac J Cancer Prev 2011;12:1771)


Interaction with RAD51

Role in DNA Repair

Uses by pathologists

● Genetic testing is important, since prophylactic oophorectomy and rigorous breast surveillance is recommended for BRCA1 or BRCA2 mutation carriers when childbearing is completed (BMC Womens Health 2010 Oct 20;10:28); risk-reducing salpingo-oophorectomy (RRSO) causes a 72% reduction in BRCA2-associated breast cancer risk without significant reduction in BRCA2-associated gynecologic cancer risk (Arch Pathol Lab Med 2009;133:1041)

Micro images

Breast: normal and hereditary cancer

Ovarian carcinoma, endometrioid type: BRCA2 and AURKA expression

Prostate carcinoma, endometrioid type: BRCA2 and AURKA expression

Positive staining - normal

● Keratinizing squamous epithelium, breast, prostate (nuclei of both luminal and basal epithelial layers in normal tissue and BPH)

Negative staining

● Loss of BRCA2 in HG PIN and prostatic adenocarcinoma (Arch Pathol Lab Med 2009;133:1041)

End of Stains > BRCA2

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