engleski

Expression of bone morphogenetic proteins in human metastatic prostate and breast cancer

The prostate and breast cancer frequently metastasize to bone. Human prostatic adenocarcinoma produces osteoblastic metastases in bone, whereas the majority of bone secondaries from breast cancers are osteolytic lesions. The mechanisms of the metastatic process to bone are poorly understood. Receant research showed different findings about BMPs expression in both prostate and breast carcinoma. The present study was centered on the BMPs expression in prostate and breast carcinoma cells with established bone metastases, as confirmed by a bone scan. The aim of this study was to explore the difference of the expression of BMP-2, -3, -4, -5, -6 and – 7 between those two tumors, as prostate carcinoma induces osteoblastic metastatic lesions in bone, whereas breast carcinoma metastasizes inducing osteolytic lesions. Primary tumor specimens from 20 patients with prostate cancer and 15 with breast cancer were studied immunohistochemistry for BMP-2/4, -3, -5, -6 and -7. All patients had multiple bone metastases as proven by bone scan. Laboratory findings and clinicopathologic parameters were obtained from clinical data. Immunopositive cells were counted on 15 randomly chosen high power fields and expressed as percentage (minimum 1, 000 cells per specimen). Our results demonstrated a different pattern of BMPs expression in human metastatic prostate and breast cancers. In prostate cancer, BMP-2/4 and BMP-5 expression were positive in all examined cases, whereas BMP-3, -6 and -7 were found positive in 15%, 55 % and 40% of cases, respectively. The percentage of positive cells varied among individual BMPs. BMP-2/4 showed the highest level of expression (83% of positive cells in all cases). All samples of breast cancer cells expressed only BMP-7, with high percentage of positive cells, too (86% positive cells). The pattern of BMPs expression in prostate cancer cells was typically cytoplasmic, whereas in breast carcinoma the staining was exclusively nuclear. Alkaline phosphatase concentrations was higher in patients with prostate cancer and differed significantly from patients with breast carcinoma. In conclusion, the results show different BMP expression in prostate and breast cancer cells, tumors with different types of bone metastasis. The prostatic carcinoma expressed all BMPs while breast carcinoma only BMP-7 independently of tumor differentiation. This may be relevant for metastasing to bone and causing osteolytic or osteoblastic reaction.

prostate cancer; breast cancer; BMPs; immunohistochemistry

doi:10.1016/j.bone.2005.04.001