Hsp27, angiogenesis and cadherins in human breast cancer biopsy

FANELLI M. A.; CUELLO CARRIÓN F. D.; GAGO F. E.; TELLO O.; CIOCCA D. R.

Mendoza, Argentina

Workshop; 3rd. International Workshop: Molecular Biology of Stress Responses; 2001

Cell Stress Society International, Fundación Argentina para la Investigación del Cáncer, Instituto de Medicina y Biologia Experimental de Cuyo

Breast cancer is a heterogeneous disease and the correct identification of the patients who will have a poor prognosis is of clinical value to provide the best treatment options and to plan the follow-up. There are several pathological and molecular prognostic factors and it is clear that the combination  of several of them will be necessary to discover the patients with poor prognosis, e.g. those developing distant metastases. In the present study we have evaluated fue prognostic significance of Hsp27 in the blood vessels of breast cancer patients correlating its expression with that of: a) coagulating factor VIll (FVIll, used to measure angiogenesis), and b) cadherins (E-cadherin and P-cadherin) and Beta-catenin. Cadherins are important molecules involved in cell-cell adhesion, some of them have been related with the prognosis of breast cancel. The study involved 113 patients, 76 with a median follow-up of 5 years. The breast cancer biopsy samples were processed for immunohistochemistry. Hsp27 could be detected in the endothelium of smaIl blood vessels as well as in the tumor cells, the number of Hsp27-positive vessels was higher in the tumor areas with infiltrating lymphocytes. There was no correlation between the presence of Hsp27-positive blood vessels and the amount of blood vessels positive for FVllI, FVIII was a better marker for angiogenesis. The expression of Hsp27 in the blood vessels did not correlate with the development of distant metastasis, however, angiogenesis (FVIll) correlated with poor prognosis (P < 0.02). Tumors expressing P-cadherin showed more Hsp27-negative blood vessels (P < 0.05). The presence of P-cadherin (but not E-cadherin) in the membrane of tumor cells was associated with poor prognosis (P < 0.02). In tumor cells, Hsp27 did not correlate with P-cadherin expression. Beta-catenin content did not correlate with disease prognosis. In summary, poor prognosis was seen in patients with P-cadherin expression and with elevated angiogenesis.