WWOX protein expression varies among ovarian carcinoma histotypes and correlates with less favorable outcome

We performed WWOX protein expression analyses by means of immunobloting and immunohistochemistry on normal ovaries and specific human ovarian carcinoma Tissue Microarrays (n = 444). Univariate analysis of clinical-pathological parameters based on WWOX staining was determined by χ2 test with Yates' correction. The basic significance level was fixed at p < 0.05.Immunoblotting analysis from normal ovarian samples demonstrated consistently strong WWOX expression while 37% ovarian carcinomas showed reduced or undetectable WWOX protein expression levels. The immunohistochemistry of normal human ovarian tissue sections confirmed strong WWOX expression in ovarian surface epithelial cells and in epithelial inclusion cysts within the cortex. Out of 444 ovarian carcinoma samples analyzed 30% of tumors showed lack of or barely detectable WWOX expression. The remaining ovarian carcinomas (70%) stained moderately to strongly positive for this protein. The two histotypes showing significant loss of WWOX expression were of the Mucinous (70%) and Clear Cell (42%) types. Reduced WWOX expression demonstrated a significant association with clinical Stage IV (FIGO) (p = 0.007), negative Progesterone Receptor (PR) status (p = 0.008) and shorter overall survival (p = 0.03).These data indicate that WWOX protein expression is highly variable among ovarian carcinoma histotypes. It was also observed that subsets of ovarian tumors demonstrated loss of WWOX expression and is potentially associated with patient outcome.The WWOX gene, originally cloned by our laboratory, spans a genomic region greater than 1 Mb in size and is the second most common chromosomal fragile site, FRA16D (16q23) [1,2]. Abnormalities affecting WWOX at the genomic and expression level have been reported in numerous neoplasias and cancer derived cell lines including, breast, ovarian, esophageal, lung, stomach, liver, pancreas and hematological malignancies [3-12]. We observed that ectopic WWOX expression inhibited anchorag