GRP94 overexpression as an indicator of unfavorable outcomes in breast cancer patients.

AIMS

This study aimed to examine the heat shock protein Hsp90 family protein (GRP94) expression in breast cancer tissues and its correlation with clinicopathologic features, including the survival of patients with breast cancer.

METHODS

GRP94 mRNA expression was examined in normal breast and breast cancer tissues using real-time PCR. We also analyzed GRP94 protein expression with immunohistochemistry in 139 breast cancer patients whose ages ranged from 29 to 83 years (median =53 years). On evaluation of cytoplasmic GRP94 immunostaining, cases with a score of ≥ or ≤ six were regarded as having high or low GRP94 expression, respectively. The relationship between GRP94 expression levels and the clinical features of breast cancer were also analyzed.

RESULTS

GRP94 mRNA expression was markedly greater in breast cancer tissues than that in normal breast tissues (P=0.0027). Immunohistochemical analysis revealed increased GRP94 protein expression in the cytoplasm of breast cancer cells, which did not positively correlate with age, tumor size classification, lymph node metastasis classification, clinical stage, or estrogen receptor expression in breast cancer patients, but did negatively correlate with progesterone receptor expression (P=0.032). Furthermore, patients with breast cancer tissue that expressed high GRP94 had a significantly shorter survival time than did patients with a low GRP94 expression (P<0.001). A multivariate analysis suggested that the level of GRP94 expression was an independent prognostic indicator (P<0.001) for the survival of patients with breast cancer.

CONCLUSION

High GRP94 expression levels were found to be an independent and unfavorable prognostic indicator of breast cancer survival.