Introduction

Ovarian cancer is the most lethal gynecologic malignancy in the United States. In 2010, over 21 880 new cases were diagnosed and 13 850 women died from this disease (1). Over the past two decades, advances in conventional therapy have led to an increase in five-year survival for women with ovarian cancer, but the fraction of long-term survivors remains unchanged at 30%, when all stages are considered. Traditional methods are unlikely to produce dramatic improvements in outcomes. Insights into the molecular mechanisms of ovarian cancers, the biological basis for their clinical behavior, and utilization of these targets are needed.

Cellular origin of ovarian cancers

Over 90% of ovarian cancers are of epithelial origin with mesothelial features. The remaining 10% are from germ cells or granulosa-theca cells within the ovary. Traditionally, epithelial ovarian cancers have been thought to originate from flattened cells covering the ovary or lining subserosal inclusion cysts (2). Recent evidence suggests that the majority of familial ovarian cancers, and as many as 20% of the primary peritoneal cancers, may arise from the fimbriae of the Fallopian tube (3). Epithelial ovarian cancers exhibit four histotypes (serous, endometrioid, mucinous, and clear cell) regulated by the different HOX genes implicated in normal gynecologic development (Table 54.1; 4,5). Ovarian cancers may be of low or high grade, correlating with stage at presentation, rate of growth, and response to chemotherapy. Ninety percent of epithelial ovarian cancers are clonal; thus, the genetic abnormalities found in primary cancers are also found in metastases, although the correlation is not always precise (6).