Aberrant expression of homeobox gene HOXA7 is associated with mullerian-like differentiation of epithelial ovarian tumors and the generation of a specific autologous antibody response

Autologous serum antibodies to molecules that are aberrantly expressed in tumors represent potential biomarkers for early diagnosis of cancer. In this study, we identified the homeobox gene HOXA7 as encoding an antigen in epithelial tumors of the ovary. These tumors are thought to arise from the simple epithelium lining the ovarian surface, but they often resemble the specialized epithelia derived from the mullerian ducts. Expression of HOXA7 was detected in ovarian tumors exhibiting muillerian-like features and correlated with the generation of anti-HOXA7 antibodies by patients. In contrast, it was observed that healthy women lack anti-HOXA7 antibodies (P < 0.0001) and that HOXA7 expression is absent from normal ovarian surface epithelium. Interestingly, HOXA7 expression was detected in the mullerian-like epithelium lining inclusion cysts in normal ovaries and in the mullerian duct-derived epithelium of normal fallopian tubes. Furthermore, ectopic expression of HOXA7 enhanced the epithelial phenotype of immortalized ovarian surface epithelial cells, as indicated by the appearance of cobblestone morphology, induction of E-cadherin expression, and down-regulation of vimentin. These findings associate aberrant HOXA7 expression with the mullerian-like differentiation of epithelial ovarian tumors and suggest diagnostic utility of serum antibodies to HOW.