Some markers were able to detect 80% of the cases, but if there is a substantial number of false negatives and the markers do not detect 100% of the cancer cases, the markers are considered failures.6,7 These failures,

in early detection and therapy, prompted the question whether we really understand the etiology and the biology of this disease. THE ORIGIN OF OVARIAN CANCER One fundamental question that has yet to be answered is the origin of ovarian cancer. In spite of numerous studies, the original lesion that gives rise to ovarian cancer has thus far not been identified. Some researchers even considered the original lesion to be created Inhibitors,research,lifescience,medical de novo.8 The prevalent theory is that ovarian cancer originates from the surface epithelium layer of the ovaries, which is of mesothelial origin. The epithelial cells involute inside the ovaries and form cysts. Subsequently, due to an accumulation of

genetic mutations, the Inhibitors,research,lifescience,medical cells turn cancerous and a tumor is formed. The problem with this theory is that there are different types of ovarian cancers. These subtypes include endometrial ovarian cancers, clear cell carcinomas, and mucinous, serous, and Brenner transitional tumors, whose cellular make-up is not necessarily mesothelial in Inhibitors,research,lifescience,medical nature (Figure 1).9 All these selleck chemicals llc cancers have diverse histological origins and different clinical and pathological behaviors. Therefore, it is unlikely that all these tumors originate from the same cell or the same lesion. The simplistic theory of the origin of ovarian cancer is even more improbable if we take into account that most of the disparate cancer Inhibitors,research,lifescience,medical cell types are not ovarian in origin.10 Figure 1 Histologically different types of ovarian cancer. While it was logical to

assume that the genesis of the ovarian tumor is the ovary, it is also logical that the progenitor cells of the ovarian tumors originate from tissues adjacent to the ovary, such as the fallopian tubes.11 Studies in which fallopian tubes were more carefully examined confirmed that small in-situ early invasive Inhibitors,research,lifescience,medical tubal carcinomas occur in women with a genetic predisposition for ovarian cancer.12 In addition, 70% of sporadic (non-hereditary) ovarian and peritoneal high-grade serous carcinomas demonstrated mucosal tubal involvement, including serous tubal intraepithelial carcinoma (STIC).13 Further support for this argument is the finding that selleck chem inhibitor nearly all STICs overexpress GSK-3 p53, similar to high-grade serous carcinoma. Laser capture micro-dissection studies have demonstrated that these lesions harbor mutated p53. In addition, STICs that are associated with a concomitant ovarian carcinoma shared not only morphologic features but also identical p53 mutations, indicating a clonal relationship.13 Therefore, it seems very likely that there is a “two-way traffic” between the ovaries and the fallopian tubes.