Stains & molecular markers
BRCA2
Copyright: 2003-2020, PathologyOutlines.com, Inc.
PubMed Search: brca2[title]
BRCA2
Author: Nat Pernick, M.D.
Topic Completed: 1 February 2013
Minor changes: 15 September 2020
Copyright: 2003-2020, PathologyOutlines.com, Inc.
PubMed Search: brca2[title]
Table of Contents
Definition / general | Uses by pathologists | Microscopic (histologic) images | Positive staining - normal | Negative stainingCite this page: Pernick N. BRCA2. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsbrca2.html. Accessed September 20th, 2020.
Definition / general
- 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)
-
Breast:
- 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
-
Ovary:
- 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)
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)
Microscopic (histologic) images
Images hosted on other servers:
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)
