Ovarian serous carcinoma: recent concepts on its origin and carcinogenesis

Worldwide, approximately 225,500 women are diagnosed with ovarian cancer annually, with an estimated 140,200 associated deaths [1]. Although ovarian cancer accounts for only 3% of all cancers in women, it has one of the highest death-to-incidence ratios, which has been primarily attributed to the unavailability of effective screening tools, the absence of early phase symptomatology in many patients, and accordingly, its typical presentation at advanced stages when prognosis is poor [2,3].As has become apparent in recent years, one of the greatest obstacles to the detection of early-stage ovarian cancer was our poor understanding of its histogenesis and pathogenesis. Ovarian carcinoma was traditionally thought to originate from the ovarian surface epithelium (OSE) or ovarian epithelial inclusions (OEI), and investigative efforts at early detection have accordingly been centered on the ovary for decades. However, these efforts have not been successful, as evidenced by the fact the overall survival for women with ovarian cancer has not changed in any fundamental manner over the last 50 years [4]. Several emerging lines of evidence indicate that some traditional tenets of ovarian epithelial carcinogenesis and cellular origination are fundamentally flawed.Patients with high-grade serous carcinoma (which constitute 60-80% of ovarian epithelial carcinomas [OEC], and which represent the archetypical "ovarian cancer") most frequently present at advanced clinical stage and have a very poor overall survival [5,6]. Therefore, understanding of the nature and development of this type is extremely important for improving the survival rate of ovarian cancer patients as a group. Recently, studies of both asymptomatic women with germline BRCA1 or BRCA2 mutations as well as those from the general population with pelvic serous carcinoma, have detected precancerous or early cancerous lesions - serous tubal intraepithelial carcinoma (STIC) - in the fallopian tubal fimbria [7-9]. Furtherm