In this week's Pathology Atlas blog post, we highlight genes with prognostic association to ovarian cancer , as September is National Ovarian Cancer Awareness Month in the US. Ovarian cancer is the fifth most frequent cause of cancer death in women, and 50% of all ovarian cancers are diagnosed in women older than 65 years of age.

Epithelial ovarian carcinoma is one of the most common gynecologic malignancy. There are five subtypes of epithelial ovarian carcinoma, of which high-grade serous carcinoma is the most common. Approximately 10% of ovarian cancers are associated with genetic factors; women with mutations in the genes BRCA1 or BRCA2 have about a 50% higher risk of developing ovarian cancer. Ovarian cancer is typically denoted as a "silent cancer" since symptoms occur late in the course of the disease. At the time of diagnosis, approximately 70% of the tumors have spread beyond the ovary and are in such cases rarely curable. The poor prognosis has prompted research efforts for early detection of ovarian cancer.

The analysis of prognostic genes in ovarian cancer was based on publically available gene expression data and clinical metadata from the Cancer Genome Atlas (TCGA) consisting of 373 women with different stages of ovarian serous cystadenocarcinoma. 143 of the patients were still alive at the time of data collection. Information on stage distribution was missing. According to the analysis 507 genes were associated with prognostic outcome, out of which 151 genes were associated with unfavourable prognosis and 366 genes associated with favourable prognosis.

Epithelial cell adhesion molecule is encoded by the EPCAM gene. The protein is a homotypic calcium-independent cell adhesion molecule and functions as a carcinoma-associated antigen. The antigen is being used as a target for immunotherapy treatment of human carcinomas. In our analysis, higher mRNA expression of EPCAM was shown to be associated with favourable prognosis in ovarian cancer patients. Immunohistochemical staining of EPCAM showed a differential membranous expression pattern in ovarian cancer samples (Figure 1).

The Keratin type II cytoskeletal 7, or KRT7, is a member of the keratin gene family. The type II cytokeratins consist of basic or neutral proteins which are co-expressed during differentiation of simple and stratified epithelial tissues. KRT7 is involved in the translational regulation of the human papillomavirus type 16 E7 mRNA (HPV16 E7). In our analysis, higher mRNA expression of KRT7 was shown to be associated with unfavourable prognosis in ovarian cancer patients. Immunohistochemical staining of KRT7 showed a differential cytoplasmic and membranous expression pattern in ovarian cancer samples (Figure 2).

The ovarian cancer proteome is described more in detail on the Pathology Atlas and information about other prognostic genes can be explored. In this serie of articles we have described prognostic markers for other cancers like prostate cancer, breast cancer and colorectal cancer. Information about how these gene markers have been identified is summarized in a previous article, and the related research article, published last month in Science (Uhlen et al. 2017).

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Åsa Näsström