Inducible heat shock protein 70 expression as a potential predictive marker of metastasis in breast tumors

Heat shock protein (Hsp)-peptide complexes purified from tumors can prime the immune system against tumor antigens, but how they contribute to the generation of immune responses against naturally occurring tumors is unknown. Murine tumors expressing high amounts of Hsp70 are preferentially rejected by the immune system, suggesting that low Hsp70 expression is advantageous for tumor growth in the host. To determine whether Hsp70 was differentially expressed in human tumors, inducible Hsp70 expression was quantitatively (by Western blot) and qualitatively (by immunohistology) analyzed in 53 biopsies of tumor and normal breast tissue. The mean expression of inducible Hsp70 was significantly higher in tumor compared with normal tissue (U = 899.0; P = 0.0033). However, a significant negative association of the amount of Hsp70 expressed by tumor tissue was found with metastasis (r = -0.309; P = 0.05). After 3 years, follow-up analysis determined that 7 of the 53 patients relapsed, and 5 died. Hsp70 expression in tumor (but not normal) cells was significantly lower in relapse patients and patients with metastatic disease than in patients with no relapse or metastasis. Together, these observations support the hypothesis that Hsp70 plays a role in tumor expansion in vivo, and tumors that downregulate it may be able to evade immunosurveillance and grow.