Antibodies to heat-shock protein 27 are associated with improved survival in patients with breast cancer.

Se Conroy,Dy Wang,Is Fentiman,Pd Sasieni,Ds Latchman,V Amin,P Smith

doi:10.1038/bjc.1998.312

Abstract

The overexpression of the heat-shock proteins hsp90, hsp70 and hsp27 in human mammary carcinomas has previously been shown to correlate with reduced overall survival. Moreover, antibodies to hsp90 were detectable in the serum of a large proportion of breast cancer patients but they were not found in normal controls. High antibody levels also correlated with reduced survival. Here, we show that antibodies to hsp27 were also detectable in the sera from breast cancer patients but not from normal controls, whereas antibodies to hsp70 were detectable in approximately one-third of both groups. The presence of antibodies to hsp27 was correlated with an improved rather than a reduced survival, particularly beyond the first 5 years. Hence, the overexpression of hsps in breast cancer cells does not provoke a generalized immune response to all the hsps. Moreover, the presence of antibodies to different hsps has distinct associations with survival. These effects are discussed in terms of the mechanisms that provoke an immune response to the hsps and the protective/non-protective effects of such a response.

Highlights

We have previously studied whether such antibodies to hsp90 could be observed in breast cancer patients
There was no significant difference in the frequency of antibodies to hsp70 in patients with breast cancer and healthy control subjects, with these antibodies being detectable in approximately one-third of both groups
Whereas over one-third of breast cancer patients had antibodies to hsp27, these antibodies were only detectable in a single normal individual (P < 0.001)

Summary

Methods

ELISA assays were carried out as described previously (Conroy et al, 1994; Faulds et al, 1995). Nunc Immuno ELISA plates were coated with hsp (0.5 gg ml-' Bioquote, UK) overnight at 4°C blocked with borine serum albumin (BSA) and goat sera (Sigma and Gibco) at 37°C. This ELISA was established using D5, a monoclonal antibody to hsp (a gift from Professor R King). A pool of sera positive for these antibodies was applied in duplicate at four dilutions on each plate. Survival has been analysed from the date of diagnosis until death because of breast cancer. All breast cancer patients at Guys are carefully followed. The survival times of women dying of causes other than breast cancer were censored at their time of death.

Results

Discussion

Conclusion