αB-crystallin expression in breast cancer is associated with brain metastasis

Abstract

BACKGROUND/OBJECTIVES: The molecular chaperone αB-crystallin is expressed in estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 ‘triple-negative’ breast carcinomas and promotes brain and lung metastasis. We examined αB-crystallin expression in primary breast carcinomas with metastatic data to evaluate its association with prognosis and site-specific metastases. METHODS: αB-crystallin gene (CRYAB) expression was examined using publically available global-gene expression data (n = 855 breast tumors) with first site of distant metastasis information (‘855Met’). αB-crystallin protein expression was determined by immunohistochemistry using the clinically annotated British Columbia Cancer Agency (BCCA) tissue microarray (n = 3,987 breast tumors). Kaplan–Meier and multivariable Cox regression analyses were used to evaluate the prognostic value of αB-crystallin. Multivariable logistic regression analysis was used to evaluate risks of αB-crystallin and other markers for site of metastasis. RESULTS: In the 855Met data set, αB-crystallin gene (CRYAB) expression was an independent predictor of brain as the first distant site of relapse (hazards ratio, HR = 1.2, (95% confidence interval, CI 1.0–1.4), P = 0.021). In the BCCA series, αB-crystallin protein expression was an independent prognostic marker of poor breast cancer-specific survival (HR = 1.3, (95% CI 1.1–1.6), P = 0.014). Among patients with metastases, αB-crystallin was the strongest independent predictor of brain metastasis (odds ratio, OR = 2.99 (95% CI 1.83–4.89), Po0.0001) and the only independent predictor of brain as the first site of distant metastasis (OR = 3.15 (95% CI 1.43–6.95), P = 0.005). αB-crystallin was also associated with worse survival (3.0 versus 4.7 months, P = 0.007). CONCLUSIONS: αB-crystallin is a promising biomarker to identify breast cancer patients at high risk for early relapse in the brain, independent of estrogen receptor and human epidermal growth factor receptor-2 status.