MHC-class-I expression in human breast cancer correlates with nuclear localization of the 90 kDa heat-shock-protein.

Breast cancer cells frequently exhibit a reduction in expression of major-histocompatibility-complex (MHC) class I proteins which blocks cytotoxic T-lymphocyte (CTL) mediated apoptosis. Recent studies indicate that the 90 kD heat-shock-protein (HSP90) plays a major role in the transfer of antigenic peptides to the MHC class I complex. HSP90 is a molecular chaperone which is involved in signal transduction and regulation of apoptosis. Since HSP90 is described to be elevated in breast cancer, its relationship with MHC class I expression was investigated. Using immunohistochemistry we analyzed the expression and localization of HSP90 and MHC class I in 17 human breast tumors. Positive correlation (p < 0.025) between strong nuclear staining for HSP90 and high MHC class I expression was observed. In tumors with reduced MHC class I expression, no nuclear localization of HSP90 was detectable. These findings lead to the hypothesis that tumor cells with high MHC class I expression and susceptibility to CTL action may escape apoptosis by a mechanism which involves increased nuclear HSP90.