Potential Tumor Biomarkers for Ovarian Cancer

Abstract

In the United States, invasive ovarian cancer is the 5th most deadly malignancy in females, accounting for an estimated 13,850 deaths in 2010 (Ahmad, 2011; American Cancer Society, 2010). The risk of dying from ovarian cancer depends on staging and varies greatly. Ovarian cancer patients diagnosed at the localized stage exhibit a 5 year survival rate of 94%. This rate is 73% when diagnosed at the regional stage following local dissemination and drops to 28% when a patient is diagnosed at the distant stage with metastasis to organs outside the pelvis. Overall, the combined 5 year survival rate for all ovarian cancer patients is an unmanageable 46% (American Cancer Society, 2010). Upon histological evaluation, most ovarian cancers are found to be epithelial in nature and are collectively referred to as ovarian epithelial cancers (OEC). The most common OEC subtypes include, in decreasing order of frequency, serous adenocarcinomas, followed by endometrioid, and smaller subsets of mucinous, clear cell, transitional, and undifferentiated carcinomas (Tavassoli and Devilee, 2003). The typical progression of invasive ovarian cancer is dissemination from the primary site into the peritoneal mesothelium. The close proximity of the ovary to the mesothelium explains the high incidence of peritoneal dissemination observed in nearly all cases of ovarian cancer. Tumors are thought to arise either from implanted cells from the fringe of the fallopian tube (Jarboe et al, 2008) or from dysplastic inclusion cysts which develop out of the mesothelial-like ovarian surface epithelium (OSE). As the tumor progresses, cells shed into the peritoneal fluid, escape apoptotic mechanisms, and begin to attach to their surrounding mesothelium via integrin-mediated interactions with extracellular matrix components (Ahmed et al, 2005; Cannistra et al., 1995; Yokoyama et al., 2007). Unlike most malignancies, ovarian cancers rarely metastasize through the hematogenous route until the advanced stages (Rose et al., 1989). Approximately 62% of cases of ovarian cancer are diagnosed at the distant stage (American Cancer Society, 2010) and the clinical prognosis for such patients is poor. The high mortality associated with ovarian cancer stems, in part, from late detection and underpins the exigent need to identify predictive and early stage diagnostic biomarkers. The task is not an easy one. Difficulty in the validation of current screening tests is mainly attributed to the lack of uniformity in clinical presentation of the disease, which varies with epithelial cell morphology, depending on whether the carcinoma is of a serous, clear cell, mucinous, or endometrioid type. To the present date, blood concentration measurements of CA125 (mucin-16), in conjunction with ultrasonography, have been used to screen for ovarian cancer. However, it has been found that detection of serum CA125 alone is