The putative tumor suppressor WWOX gene spans 1Mb genomic region at the second most common chromosomal fragile site, FRA16D (16q23). Loss of heterozigosity affecting the WWOX region is commonly observed in prostate carcinomas. BAC and expression microarrays studies also suggest that WWOX is one of the most likely targets for abnormalities affecting chromosome 16q in prostate cancer. Interestingly, using genetic linkage approaches the genomic region where WWOX precisely maps has been identified as an area statistically significant for harboring a prostate cancer susceptibility and tumor aggressiveness gene.The aim of this study is to correlate protein expression abnormalities affecting WWOX protein product in prostate cancer with clinico-pathological parameters. WWOX protein expression pattern was analyzed by means of immunohistochemistry, on prostate specific Tissue Microarrays (TMA) and whole sections, from normal prostate (n=13) , benign prostatic hyperplasia (BPH) (n=19) and invasive prostate carcinomas (IPC) (n=350) . Prostate specific TMAs were provided by the Cooperative Prostate Cancer Tissue Resource (CPCTR) funded by NCI.The distribution of WWOX protein expression in normal prostate showed an intriguing pattern displaying a remarkable strong positive staining for the basal cell layer compartment and only moderate staining for the luminal cells compartment . The BPH samples were equivalent to normals in terms of pattern and staining intensity. The currently ongoing analysis of the prostate TMA indicate that aproximately 25-30% IPC cases showed a negative/weak staining, 45% showed moderate and 30% showed strong positive staining. In our preliminary analysis a tendency of decreasing WWOX expression was observed depending on higher Gleason Score (Gleason sum) i.e. the less differentiated the tumor the less WWOX expressed . We are currently analyzing WWOX protein expression pattern with clinical parameters as well as Androgen Receptor status. We hypothesize that WWOX is the target for genomic abnormalities affecting the region 16q33 in prostate cancer. We speculate that WWOX is a tumor suppressor gene and that its loss of expression is relevant in cancer progression. Since WWOX is and oxidoreductase enzyme likely involved in sex steroid metabolism an association may also exist between loss of WWOX expression and loss of androgens dependence in prostate cancer. Supported by RO1 CA102444-01

[Proc Amer Assoc Cancer Res, Volume 46, 2005]