Hsp27 and Hsp70 in serial biopsies from breast cancer patients treated with doxorubicin

VARGAS ROIG, L.M.; DAGUERRE, P.; LEUZZI, M.; GAGO, F.E.; NADIN, S.B; LAZZARO, M.A.; CIOCCA, D.R.

San Francisco, California, USA

Congreso; 93rd Annual Meeting of the American Association for Cancer Research; 2002

American Association for Cancer Research

Heat shock proteins (Hsps) may be expressed in human breast cancers. In a previous study we observed, that the administration of doxorubicin, 5-fluoruracil and cyclophosphamide increased Hsp27 and Hsp70 nuclear expression and decreased the cytoplasmic content of Hsp70 in biopsies from breast cancer patients. These changes were relatively late events because the post-chemotherapy biopsies were taken approximately 21 days after the last cycle of induction chemotherapy. In the present study, we decided to evaluate the expression of Hsp27 and Hsp70 in serial biopsies from a more homogeneous group of breast cancer patients. The study involved patients with locally advanced disease treated only with 75 mg/m2 of doxorubicin during 4 cycles before the surgery as the initial treatment. The serial biopsies were taken at pre-chemotherapy, at days 1, 3, 7, 21, and at surgery. Forty two patients entered into this protocol, after surgery patients received 6 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil. We evaluated by immunocytochemistry Hsp27 and Hsp70 expression in carcinomas (invasive and in situ) and in normal tissues (breast ephitelium, fibroblasts, endothelium and lymphoid infiltration). In invasive tumors, an increased nuclear expression of Hsp27 and Hsp70 was found as a relatively late event, it was significant at surgery (p<0.01 and p<0.001 respectively). No significant changes were noted in the cytoplasmic content of both Hsps. Hsp27 and Hsp70 were also expressed in the plasma membrane of tumor cells in 43% and 29% of the cases respectively. In normal breast ephitelium, cytoplasmic and nuclear expression of Hsp27 was lower than in the invasive tumor, specially at surgery (p<0.001). In in situ carcinomas, Hsp27 cytoplasmic expression was higher than in the invasive tumor cells reaching statistically significant differences up to day 7 (p<0.001). In normal breast epithelium, nuclear Hsp70 content increased at days 1 and 3 and decreased at days 7 and 21, but at surgery nuclear Hsp70 was increased (p<0.001). After chemotherapy Hsp70 increased in activated fibroblasts and lymphocytes (p<0.001). In endothelium, we observed a slight increase in the expression of Hsp27 and Hsp70 after chemotherapy. These results showed that tumor cells and normal cells in human breast tissue respond to the stress induced by doxorubicin with a particular dynamics in the expression of Hsp27 and Hsp70.