HER-2/neu gene amplification status in prostate cancer by fluorescence in situ hybridization

HER-2/neu expression has been established as a prognostic factor in breast and other cancers. In prostate cancer (PC), a similar predictive role has been hindered by variable immunohistochemical (IHC) results. The authors studied DNA amplification of the HER-2/neu gene on 4-microm sections obtained from 62 formalin-fixed, paraffin-embedded PCs by fluorescence in situ hybridization (FISH). The results were compared with HER-2/neu protein expression as determined by IHC and correlated by logistic regression analysis with Gleason tumor grade, DNA ploidy, serum prostate specific antigen (PSA), and pathological stage. The HER-2/neu gene was localized using the Oncor (Gaithersburg, MD) digoxigenin-labeled unique sequence probe. Amplified PCs had at least 20 malignant cells, with 5 or more copies of the sequence. Amplification of HER-2/neu correlated with Gleason score (P = .0001). The mean Gleason score of unamplified tumors was 5.7 and that of amplified tumors was 7.5. Nondiploid tumors had a significantly greater rate of HER-2/neu amplification compared with diploid tumors (P = .0003). Of the 62 cases evaluated by IHC and FISH, 18 cases (29%) were overexpressed by IHC, and 27 cases (44%) were amplified by FISH. A trend for similar HER-2/neu status in each PC by the two methods did not reach statistical significance (P = .23). HER-2/neu amplification by FISH was associated with advanced pathological stage; however, this relationship reached only near-statistical significance (P = .06). There was no correlation of HER-2/neu amplification by FISH with patient age or preoperative serum PSA levels. The authors conclude that HER-2/neu gene amplification status can be determined by FISH on archival prostate cancer specimens, significantly correlates with high tumor grade and nondiploid DNA content, and is more frequently encountered in tumors with advanced pathological stage. Also, FISH is more sensitive than IHC for detection of abnormalities in the HER-2/neu gene, and further studies should be undertaken to determine whether a FISH-based HER-2/neu detection method may prove of importance in the prediction of prognosis and planning of therapy in prostate cancer patients.