Abstract
Epithelial ovarian cancer is morphologically heterogeneous being classified as serous, endometrioid, clear cell, or mucinous. Molecular genetic analysis has suggested a role for tumor suppressor genes located at chromosome 10q in epithelial ovarian cancer pathogenesis. Our objective is to evaluate the expression of ANXA7, a novel tumor suppressor gene located on 10q21, in these epithelial ovarian cancer subtypes, and to investigate its correlation with patient survival. ANXA7 is ubiquitously expressed in small amounts in nearly every normal cell and the Anxa7 (+/-) knockout mouse has a cancer prone phenotype. Altered ANXA7 protein levels are associated with prognostically challenging aggressive forms of prostate and breast cancer. So far, information is not available regarding the association of ANXA7 expression in ovarian cancer and patient survival. Therefore, we used human tumor tissue microarray (TMA) technology in order to evaluate the ANXA7 immunoreactivity as possible diagnostic and/or prognostic marker of ovarian cancer by immunoperoxidase assay using ANXA7 monoclonal antibody. Using a 129 case diagnostic human tumor tissue microarray, we report that the expression of ANXA7 is significantly reduced and is associated with disease progression. Furthermore, using a separate 301 case retrospective prognostic tumor tissue microarray, we find that loss of ANXA7 expression is also significantly associated with poor over-all patient survival. We conclude that ANXA7 may be a new prognostic marker or a target for improving the treatment efficiency of patients with ovarian cancers.
Highlights
Ovarian cancer is the fourth leading cause of cancer-related death in women in the U.S and the leading cause of gynecologic cancer death [1]
In our work with the Anxa7 knockout mouse we found that the nullizygous Anxa7 (-/-) mutant is embryonically lethal and the Anxa7 (+/-) animals developed profoundly increased frequency of tumors compared to the Anxa7 (+/+) normal littlermate controls
Loss of ANXA7 expression is associated with ovarian disease progression
Summary
Ovarian cancer is the fourth leading cause of cancer-related death in women in the U.S and the leading cause of gynecologic cancer death [1]. Epithelial ovarian cancer (EOC) is characterized by few early symptoms, presentation at an advanced stage, and poor survival. Finding a reliable biomarker or a target that could be used to individualize both patient prognosis and therapy is essential for the prevention and cure of ovarian cancers. The finding of a novel tumor suppressor gene (ANXA7) in a chromosomal region (10q21) with frequent mutations/deletions in human cancers raises important questions as to its use as a prognostic factor for the ovarian cancer. Tumor frequency is in the range of 20-50% of animals, becoming more accentuated with advancing age [8]. Using a human prostate and breast tissue microarray, we found that alterations of ANXA7 protein expression is associated with metastases and hormone insensitive local recurrent cancers. We found that allelic loss of the ANXA7 gene occurs in over one third of primary carcinoma of the prostate and breast [9,10]
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