A 27 kDa heat shock protein that has anomalous prognostic powers in early and advanced breast cancer

Abstract

Summary This paper describes a prospective immunohistochemical analysis of 27 kDa heat shock protein (HSP27) in 361 patients with primary breast cancer in relation to disease-free survival (DFS) and survival from first relapse (SR). Oestradiol (ER) and progesterone (PR) receptors were also quantitated and related to the HSP27 data. While ER positively predicted a good outcome for both DFS and SR, HSP27 positivity predicted a prolonged SR but short DFS. The association between HSP27 and DFS only attained statistical significance in node-negative patients. Subgroup analysis reinforced the complementary relationship of HSP27 and ER for SR and opposing influences for DFS. In both node-negative and node-positive women, ER' HSP27-patients had a longer DFS than ER-HSP27+ counterparts. There was no relationship between HSP27 and overall survival. HSP27 staining was highly correlated with ER but not PR, patient age, tumour size or menstrual status. There was a marginal correlation (P = 0.04) with histological grade with welldifferentiated tumours having the highest HSP27. Cox multivariate regression analysis of the contribution of HSP27 in the presence of data on ER, PR, stage, nodal status and histological grade indicated that HSP27 was not of independent prognostic importance for DFS or overall survival and was only of borderline significance for OS (P< 0.07). However, in the absence of ER and PR data, HSP27 staining is an effective way of getting the same prognostic infonnation. HSP27 staining appears to correlate with different biological features in early and advanced breast, high HSP27 being linked with short DFS in node-negative patients but with prolonged survival from first recurrence.

Hsp-27 Expression in Invasive Ductal Breast Carcinoma

“…These results conflict with recently published data which demonstrated that Hsp-27 expression was inversely correlated with the grade of malignancy of invasive ductal breast cancer [26]. In astrocytoma and hepatocellular cancer, Hsp27 expression was positively correlated with grade of malignancy [27][28][29].…”

“…Our study did not show any correlation between Hsp27 expression and the expression of ER and PR. Our data is in agreement with similar results obtained by others [26,[35][36][37][38], although the study by Ciocca et al described a positive correlation between Hsp27 and ER [16]. This discrepancy needs further investigation.…”

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

“…The data presented here show that antibodies to hsp27 were present at enhanced levels in breast cancer patients paralleling the previously observed overexpression of the protein (Thor et al, 1991;Love and King, 1994). Similar results have also been obtained previously for hsp90 both at the mRNA (Jameel et al, 1992(Jameel et al, , 1993) and the antibody levels.…”

“…Some members of the hsp70, hsp27 and hsp9O families have been suggested to play a defined role in human breast cancer (for review see Conroy and Latchman, 1996). Thus, for example, overexpression of hsp27 has been associated with shorter disease-free survival in two independent studies (Thor et al, 1991;Love and King, 1994). Similarly, in patients without nodal involvement, high expression of hsp70 was associated with shorter diseasefree survival and, in patients who had undergone chemotherapy, was the only independent predictor of survival (Ciocca et al, 1993).…”

Heat Shock Proteins in Chronic Lymphocytic Leukaemia

“…However, there are contradictions within the literature; In breast cancer, for example, increased levels of HSPB1 have been associated with prolonged survival in oestrogen receptor-negative cases (Love & King, 1994). Low levels of HSPB1 in ovarian cancer have also been found to correlate with decreased survival (Geisler et al 2004).…”