Abstract 1176: αB-Crystallin expression across different stages and subtypes of breast cancer analyzed using tissue microarrays
Authors: Lubin Gabrielle P. , Khramtsov Andrey , Khramtsova Galina , Sveen Walmy E. , Perou Charles M. , Huo Dezheng , Olopade Olufunmilayo I. 
Published: February 2011

Background: Cancer biology investigations have produced many biomarkers for breast tumor diagnosis, prognosis and for therapeutic decision making. One of the potentially new important biomarkers is αB-crystallin. Previous studies have demonstrated the high prevalence of αB-crystallin positivity in basal-like breast cancer. What has not been adequately explored yet is the expression of αB-crystallin within the different stages of breast tumor progression. This study examines whether the expression of αB-crystallin changes during the progression, and if the expression varies by subtypes of breast cancer.

Methods: Immunohistochemical assays were performed on tissue microarrays consisting of 190 patients with different stages and subtypes (basal-like, luminal A, luminal B, and HER2) of breast cancer from The University of Chicago. IHC was performed using the mouse monoclonal antibody to αB-crystallin (SPA-222; 1:200, Stressgen Biotechnologies), which was evaluated as was described by Moyano et al. (2006). Breast cancer subtypes were also defined using IHC assays as previously described.

Results: Localization of αB-crystallin expression varied by tissue types: in the normal breast epithelium, αB-crystallin was expressed mainly in basal/myoepithelial layer (96% of patients) rather than luminal layer (1%). Within in situ carcinomas we found that 70% of patients expressed this biomarker in basal/myoepithelial layer and 14% of patients expressed it in the tumor cells. αB-Crystallin was expressed in 60% (3/5) of patients with basal-like DCIS, compared to 5% (2/39) of patients with luminal A DCIS (p=0.001). αB-Crystallin was expressed in 81% (26/32) of patients with invasive basal-like cancer, compared to 5% (3/66) of patients with invasive luminal A breast cancer (p&lt;0.001). αB-Crystallin was also positively correlated with tumor grade (rho= 0.23, p=0.01). As shown before, expression of αB-crystallin was associated with a worse overall survival (p=0.02), showing a hazard ratio of 1.48 for weakly positive and 1.96 for strongly positive staining compared with negative staining. We also saw a trend toward significance that αB-crystallin predicted survival within patients with basal-like breast cancer. Expression of αB-crystallin was not correlated with tumor size, lymph node involvement, stage, or race.

Conclusions: We found that αB-crystallin expression was strongly associated with the basal-like breast cancer subtype, as has been reported before. Importantly, we also found that the expression of αB-crystallin was observed in DCIS stage of breast cancer, especially in basal-like DCIS. αB Crystallin can serve as additional biomarker for basal-like carcinomas in the pre-invasive stage of tumors. Identification of this phenotype in early stage breast cancer can serve as a prognostic marker.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1176.