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HER‐2/ neu is overexpressed infrequently in patients with prostate carcinoma
Author(s) -
Lara Primo N.,
Meyers Frederick J.,
Gray Carl R.,
Gandour Edwards Regina,
Gumerlock Paul H.,
Kauderer Caren,
Tichauer Garrett,
Twardowski Przemyslaw,
Doroshow James H.,
Gandara David R.
Publication year - 2002
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.10526
Subject(s) - medicine , immunohistochemistry , trastuzumab , docetaxel , prostate , breast carcinoma , carcinoma , oncology , chemotherapy , pathology , cancer , breast cancer
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 patient, 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 patient. 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. Cancer 2002;94:2584–9. © 2002 American Cancer Society. DOI 10.1002/cncr.10526