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Table of Contents
Definition / general | Pathophysiology / etiology | Clinical features | Uses by pathologists | Diagrams / tables | Microscopic (histologic) images | Positive staining - normal | Negative stainingCite this page: BRCA1. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/stainsbrca1.html. Accessed July 12th, 2017.
Definition / general
- Breast cancer type 1 susceptibility protein
- Tumor suppressor gene at 17q21; 220 kDa nuclear phosphoprotein, 1863 amino acids with 7.8 kb mRNA (OMIM 113705, Wikipedia)
Pathophysiology / etiology
- 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
- Overexpression suppresses estrogen receptor transactivation
Clinical features
- 185delAG and 5382insC mutations are common in Ashkenazi Jews
- BRCA1 and BRCA2 mutations in Ashkenazi Jews have 2% prevalence vs. 0.1% of rest of population
Breast: - Normally expressed at puberty and pregnancy
- Interacts with cyclin dependent kinases; inhibits tumor growth in cell culture
- Accounts for 5% (age < 40 years) to 1% (age 50-70 years) of breast cancer cases in general population
- Patients with BRCA1 or BRCA2 mutation have 35%-80% lifetime risk of breast cancer by age 70
- BRCA1 associated breast carcinomas are usually high grade, aneuploid with basal / myoepithelial phenotype of P-cadherin+ EGFR+ ER- PR- HER2- (Mod Pathol 2005;18:1305)
- Higher risk of breast cancer with 300 T > G mutation
- However, BRCA1 or BRCA2 mutation is also associated with medullary carcinoma of breast, which has more favorable prognosis
Colon: - Relative risk of 4.0 for adenocarcinoma
Ovary: - 30-60% lifetime risk of adenocarcinoma in women with mutations
- Usually associated with serous cystadenocarcinoma; may be detectable only by thin sectioning and examination of entire ovary and fallopian tube (Am J Surg Pathol 2009;33:1878)
- Often younger age and high stage
- BRCA mutations cause 90% of hereditary cases of ovarian carcinomas, which account for 10% of all ovarian carcinomas (Hum Pathol 2005;36:861)
Prostate: - Relative risk of 3.0 for adenocarcinoma
Uses by pathologists
- Immunostaining in high-grade serous ovarian carcinomas may be useful to stratify patients for germline genetic testing (loss of staining is abnormal, Am J Surg Pathol 2013;37:138)
Diagrams / tables
Roles of BRCA1 and BRCA2 in DNA repair
Position on #17
Microscopic (histologic) images
High grade serous ovarian tumors with BRCA1 mutations
Positive staining - normal
- Ovarian epithelium
Negative staining
- Loss of staining seen in high grade serous ovarian carcinoma
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