Abstract
BackgroundalphaB-crystallin is a small heat shock protein that has recently been characterized as an oncoprotein correlating with the basal core phenotype and with negative prognostic factors in breast carcinomas. The purpose of this study was to evaluate alphaB-crystallin with respect to clinicopathological parameters and the outcome of patients with operable high-risk breast cancer.MethodsA total of 940 tumors were examined, derived from an equal number of patients who had participated in two randomized clinical trials (paclitaxel-containing regimen in 793 cases). Immunohistochemistry for ER, PgR, HER2, Ki67, CK5, CK14, CK17, EGFR, alphaB-crystallin, BRCA1 and p53 was performed. BRCA1 mutation data were available in 89 cases.Resultsalphaβ-crystallin was expressed in 170 cases (18.1%) and more frequently in triple-negative breast carcinomas (TNBC) (45% vs. 14.5% non-TNBC, p < 0.001). alphaB-crystallin protein expression was significantly associated with high Ki67 (Pearson chi-square test, p < 0.001), p53 (p = 0.002) and basal cytokeratin protein expression (p < 0.001), BRCA1 mutations (p = 0.045) and negative ER (p < 0.001) and PgR (p < 0.001). Its overexpression, defined as >30% positive neoplastic cells, was associated with adverse overall survival (Wald’s p = 0.046). However, alphaB-crystallin was not an independent prognostic factor upon multivariate analysis. No interaction between taxane-based therapy and aβ-crystallin expression was observed.ConclusionsIn operable high-risk breast cancer, alphaB-crystallin protein expression is associated with poor prognostic features indicating aggressive tumor behavior, but it does not seem to have an independent impact on patient survival or to interfere with taxane-based therapy.Trial registrationsACTRN12611000506998 (HE10/97 trial) and ACTRN12609001036202 (HE10/00 trial).
Highlights
AlphaB-crystallin is a small heat shock protein that has recently been characterized as an oncoprotein correlating with the basal core phenotype and with negative prognostic factors in breast carcinomas
Clinicopathological characteristics of patients and tumor subtyping A total of 940 patients with available Formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks and successful assessment of alphaB-crystallin were included in the analysis
In this study we found that alphaB-crystallin is associated with basal core phenotype (BCP) and BRCA1 mutational status but not with BRCA1 protein expression
Summary
AlphaB-crystallin is a small heat shock protein that has recently been characterized as an oncoprotein correlating with the basal core phenotype and with negative prognostic factors in breast carcinomas. Small heat shock proteins (sHsps) are molecular chaperones and are expressed in response to a wide variety of unfavorable physiological and environmental conditions, playing a cytoprotective role Their importance is reflected by the conservation of the a-crystallin structure from bacteria to humans [1]. Several studies have suggested that alphaB-crystallin expression is correlated with high histological grade, metastatic potential, poor clinical outcome and chemotherapy resistance in breast carcinomas [7,16,18]. It is more commonly expressed in basal-like breast carcinomas (BLBC) and it is thought to contribute to their aggressive phenotype [19]
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