Background: The overexpression of HER-2/neu is found in 20-30% of patients with breast carcinoma and is an adverse prognostic factor. HER-2 overexpression also has been reported in up to 60% of patients with hormone-refractory prostate carcinoma (HRPC) and was correlated with shortened survival. Trastuzumab (Herceptin) is a humanized monoclonal antibody that binds to the HER-2 receptor and has antitumor activity in patients with HER-2-overexpressing breast carcinoma. The authors report the results of HER-2 screening from a Phase II trial of chemotherapy with trastuzumab and docetaxel in patients with HER-2-overexpressing prostate carcinoma.
Methods: Archival paraffin embedded tumor tissue was obtained from potentially eligible patients and was screened for HER-2 expression by immunohistochemistry (IHC) using a specialized test kit. Shed HER-2 antigen in serum also was determined using an enzyme-linked immunosorbent assay (ELISA). HER-2 gene amplification was assessed by fluorescent in situ hybridization (FISH). Patients with IHC scores of 2+ or 3+ were considered to have HER-2 overexpression and were eligible for the trial. To date, 62 patients with HRPC have been screened.
Results: The median patient age was 72 years, and Gleason scores were < 5 in 1 patients, 5-7 in 24 patients, > 7 in 23 patients, and not specified in 14 patients. IHC HER-2 expression was 0 in 28 patients, 1+ in 14 patients, 2+ in 4 patients, and 3+ in 1 patients. Fifteen patients had either suboptimal tissue (13 patients) for interpretation or had pending results (2 patients). Therefore, 8% of all patients screened (5 of 62 patients) had HER-2 overexpression by IHC. Quantitative ELISA for shed HER-2 was available in 32 patients; this level was elevated (> 15 ng/mL) in only 2 patients, and neither had HER-2 expression by IHC. Of the 5 patients with 2+ or 3+ HER-2 expression by IHC, none had elevated shed HER-2 antigen levels by ELISA. FISH for HER-2 amplification was performed on 12 specimens; 5 of these specimens were uninterpretable due to specimen artifact, and none of the remaining 7 specimens had HER-2 amplification, defined as a ratio > 1. Patient age and Gleason score were not correlated with HER-2 status.
Conclusions: Unlike breast carcinoma and contrary to prior reports, HER-2 overexpression by IHC in archival prostate tissue from patients who eventually developed hormone-refractory disease was infrequent. There did not appear to be any correlation between HER-2 overexpression by IHC and shed HER-2 antigen levels in serum by ELISA in this tumor type. Whether trastuzumab possesses single-agent activity or modulates chemotherapy response in tumor types other than breast carcinoma remains to be determined.