Ovarian cancer is the most lethal gynecologic malignancy and the five-year survival rate is only 35% after diagnosis. Epithelial ovarian cancer is a highly metastatic disease characterized by widespread peritoneal dissemination and ascites. The death incidences from ovarian cancer could be significantly lowered by developing new methods for the early diagnosis and treatment of this fatal disease. Several potential markers have been identified recently. However, mucins are the most promising markers for ovarian cancer diagnosis. Mucins are large extracellular, heavily glycosylated proteins and their aberrant expression has been implicated in the pathogenesis of a variety of cancers, including ovarian cancer. This review will summarize known facts about the pathological and molecular characteristics of ovarian cancer, the current status of ovarian cancer markers, as well as general information about mucins, the putative role of mucins in the progression of ovarian cancer and their potential use for the early diagnosis and treatment of this disease.
The life-time risk of having ovarian cancer is 1 in 70 women. This is the fifth leading cause of death for women in developing countries. According to epidemiological studies, age is a common risk factor of ovarian cancer because the ovaries of post-menopausal women become smaller and folded. This folding results in deep cleft formations and formation of smaller cysts lined with ovarian surface epithelial (OSE) cells. The other risk factors are: nulliparity, family history, history of fertility drug use and endocrine disorders. Multiparity, use of oral contraceptives, pregnancy and lactation all are associated with lower risk of ovarian cancer because of the decreased number of ovulation cycles. Molecular alterations are also known to occur in ovarian cancer. These molecular alterations include mutation in the p53 gene which is known to be involved in DNA damage repair. Mutation in BRCA1 and BRCA2 has also been reported in ovarian tumors. Inactivation or downregulation of tumor suppressor genes and amplification of oncogenes is also a potential cause of ovarian cancer. In ovarian tumors, the downregulation of OVCA1 and OVCA2 (tumor suppressor genes present in normal ovary) is reported, while their functions in normal ovary are not well known. In contrast, overexpression/amplification of certain oncogenes like C-MYC, RAS, AKT, EGFR (ErbB1 or HER1), HER2/neu (ErbB2), CSF1 C-MYC, etc., is also well known in ovarian tumors.
Being that 90% of ovarian cancers are of epithelial origin, mucins may be attractive candidates for the detection of early stage ovarian cancer. Mucins, large extracellular proteins, are heavily glycosylated with oligosaccharides and are generally known for providing protection to the epithelial tissues under normal physiological conditions. Mucins are usually secreted by the epithelial tissues which remain in contact with relatively harsh environments such as airway epithelium, stomach epithelia, epithelial lining of intestine and ductal epithelial tissue of liver, pancreas, gall bladder, salivary gland, lachrymal gland, etc. In these tissues, epithelial cells are exposed to a variety of microorganisms, toxins, proteases, lipases, glycosidases and diverse microenvironment fluctuations that includes pH, ionic concentration, oxygenation, etc. All mucins share general characteristics. For example, they have repetitive domains of peptides rich in serine, threonine, and proline in their backbone. Serine and threonine are sites for O- and N-glycosylation. Presence of the tandem repeat domain which varies in number, length and O-glycosylation is the common structural feature of all mucins. Their general structure and biochemical composition provides protection for the cell surface and specific molecular structures regulate the local microenvironment near the cell surface. In addition, mucins also communicate the information of the external environment to the epithelial