Classification of Ovarian Cancer: A Genomic Analysis

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Ovarian cancer is the most lethal gynecologic cancer, accounting for over 16,000 deaths. In the US annually (1). The poor prognosis of this disease is due to the lack of reliable screening tools, the late stage of disease at the time of diagnosis, the high rate of recurrence of the disease, and the poor response to chemotherapy in the recurrent setting. Patients who present with stage I disease have over 90% 5-year survival, while those diagnosed with stage III disease have less than 20% 5-year survival (2). However, only 25% of patients with ovarian cancer are diagnosed with stage I disease (1). Despite new chemotherapeutic regimens and radical surgical debulking procedures, only minimal improvement in overall survival has been appreciated in the last several decades.

Epithelial ovarian cancer encompasses four major histotypes: papillary serous, endometrioid, mucinous, and clear cell. These histotypes resemble various müllerian cell types, with serous tumors resembling Fallopian tube, endometrioid tumors resembling uterine endometrium, mucinous tumors resembling the endocervix, and clear cell tumors resembling endometrial glands during pregnancy (2). Tumors are graded from 1 to 3, with grade 3 being the most poorly differentiated. Tumors of low malignant potential (LMP) display the atypical cellular features of cancer, but do not invade into the ovarian stroma (2).

The clinical characteristics of ovarian tumors vary according to histology and grade. Although clear cell ovarian cancer usually presents with earlier stage of the disease, there is a higher rate of recurrence among these patients. In fact, the 5-year survival for patients with stage I of clear cell ovarian cancer is only 60% (2). Late stage clear cell cancer also carries a worse prognosis when compared with papillary serous cancer, with an overall median survival of 12 months compared with 22 months (3). Mucinous cancers have a poorer response to chemotherapy and worse survival than the other epithelial ovarian histotypes (4). Patients with endometrioid ovarian cancers tend to have a better prognosis. Higher tumor grade correlates with poorer prognosis. Patients with LMP tumors have a 5-year survival over 95%. Among patients with early stage of disease, the survival drops down from 97% for patients with grade I tumors to 50% for those with grade III tumors (5).