The relationship between tyrosine-phosphorylated erbB-2 (p-erbB-2) expression and tumor development in patients with prostate cancer.
Nagasaki Graduate University School of Medicine, Nagasaki, Japan
AIM. ErbB-2 protein (also known as Her-2/neu) is a membrane receptor tyrosine kinase. Overexpression of the c-erbB-2 has been correlated with poor prognosis in several malignancies. Concerning prostate cancer, c-erbB-2 overexpression was reported to be associated with tumor grade, stage, and prognosis. On the other hand, several reports showed that no association was observed between erbB-2 protein overexpression and tumor stage and proliferation. Despite the tyrosine kinase receptor, role of tyrosine-phosphorylated erbB-2 (p-erbB-2) in prostate cancer is not clear. To determine whether the overexpression of erbB-2 protein or p-erbB-2 protein is involved in tumor growth and progression, we examined the distribution of p-erbB-2 expression in pretreatment biopsies from patients with prostate cancer. METHODS. Biopsy sections removed from 55 patients were examined by immunohistochemistry. For evaluation of p-erbB-2 expression, we used phospho-specific c-erbB-2 mouse monoclonal antibody (Ab-18, clone PN2A). This antibody is well known to be high specific to the tyrosine-phosphorylated (P-Tyr1248) form of erbB-2. We also examined the proliferation index (PI) by using anti-Ki-67 antibody. The correlation between the above variables and tumor features was analyzed statistically. RESULTS. Of 55 biopsy samples, 35 (54.5%) and 23 samples (41.8%) were positive for erbB-2 and p-erbB-2, respectively. ErbB-2 expression did not correlate with tumor progression (locally confined or not, p=0.09) and PI (p=0.14). However, sections with p-erbB-2 expression-positive correlated with tumor progression (p< 0.01) and high PI (p< 0.01). On the other hand, pretreatment serum PSA levels did not show significant difference between patients with erbB-2 expression-positive and those with p-erbB-2 expression-positive. In addition, both of erbB-2 and p-erbB-2 expression did not correlate with tumor grade (p=0.08). CONCLUSION. These data suggested that the expression of p-erbB-2 protein is a potentially useful marker for tumor progression and proliferation of primary prostate cancer.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 893 (Molecular pathology).