Expression Of HSF₁ And HSPs As Well As Their Relations With Prognosis And Multidrug Resistance In Breast Cancer

Objective To examine the expression of HSF1 and HSPs(HSP27, HSP70 and HSP90 a ) and to investigate the relationship between the expression and prognosis as well as multidrug resistance on protein and mRNA levels in primary breast cancer patients. Methods We performed a reverse transcription polymerase chain reaction (RT-PCR) study measuring mRNA expression levels of HSF1, HSPs and MDR1/Pgp in 30 patients and an immunohistochemistry (IHC) study on protein level in 62 patients. Expression of HSF1, HSPs and MDRi/Pgp in the carcinomas were studied on (i) relations with disease-free survival (DFS) and overall survival (OS), (ii) relations to clinicopathological factors, (iii) their expression diversity between primary carcinomas and axillary metastatic lymph nodes, (iv) their expression correlations between each other. Results Results obtained by both methods were almost concordant. (i)Expression of HSF1, HSPs and MDR1/Pgp in breast cancer specimens were markedly higher than those in normal breast samples on both protein and mRNA levels, (ii) The carcinoma which negatively expressed HSF1, HSP70, HSP90 a and Pgp seemed to have a longer DFS and a longer OS than those of expressing positively. Through Cox multivariate regression analysis, we found that axillary metastatic lymph node numbers, histological grades, HSP90 a expression and tumor size showed significant associations with DFS and OS. Pgp expression was also at the risk of a shorter OS, (iii)There were no relations between expression of HSF1, HSPs, MDR1and clinicopathological factors on mRNA level. But IHC analysis showed an association between HSF1 expression and post-menopausal status, besides, expression of HSP70 were also linked with tumor size and positive axillary nodes, (iv) There were positive correlations between HSF1 and MDR1, HSP70 and HSP27, HSP70 and HSP90 a on both protein and mRNA levels. Otherwise, HSF1 also had a positive correlation with both HSP70 and HSP90 a on protein level and MDR1 correlated positively with HSP90 a on mRNA level. We also found that expression levels of HSP90 a in primary tumors were higher than those in metastatic axillary lymph nodes. Conclusion Expression of HSF), HSP70, HSP90a , MDR1/Pgp were correlated with shorter DFS or OS in breast cancer patients, and expression of HSP90 a is suggested to be a prognostic marker for both the shorter DFS and OS. HSF1 expression was strongly linked with expression of MDR1/Pgp on both protein and mRNA levels, there were also correlations between HSF1 and HSPs on protein level, so HSF1 is hoped to be a target factor to reverse multidrug resistance and improve prognosis in breast cancer patients.