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 br east 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-mu m sections obtained from 62 formalin-fixed, paraffin-embedded PCs by flu orescence in situ hybridization (FISH). The results were compared with HER-2/neu protein expression as determined by MC and correlated by lo gistic regression analysis with Gleason tumor grade, DNA ploidy, serum prostate specific antigen (PSA), and pathological stage. The HER-2/ne u gene was localized using the Oncor (Gaithersburg, MD) digoxigenin-la beled unique sequence probe. Amplified PCs had at least 20 malignant c ells, with 5 or more copies of the sequence. Amplification of HER-2/ne u correlated with Gleason score (P=.0001). The mean Gleason score of u namplified tumors was 5.7 and that of amplified tumors was 7.5. Nondip loid tumors had a significantly greater rate of HER-2/neu amplificatio n compared with diploid tumors (P=.0003). Of the 62 cases evaluated by MC and FISH, 18 cases (29%) were overexpressed by MC, and 27 cases (4 4%) were amplified by FISH. A trend for similar HER-2/neu status in ea ch PC by the two methods did not reach statistical significance (P=.23 ). HER-2/neu amplification by FISH was associated with advanced pathol ogical stage; however, this relationship reached only near-statistical significance (P=.06). There was no correlation of HER-2/neu amplifica tion by FISH with patient age or preoperative serum PSA levels. The au thors conclude that HER-2/neu gene amplification status can be determi ned by FISH on archival prostate cancer specimens, significantly corre lates with high tumor grade and nondiploid DNA content, and is more fr equently 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 importan ce in the prediction of prognosis and planning of therapy in prostate cancer patients. HUM PATHOL 28:827-833. Copyright (C) 1997 by W.B. Sau nders Company.