Biology and Prognosis of Ovarian Neoplasms

The prognosis of ovarian cancer can be correlated with numerous clinical and biologic factors. Tumor stage, grade, and size of metastatic disease after resection correlate best with outcome. As discussed below, among patients with low stage disease, tumor grade correlates with prognosis (ie, patients with stage I high-grade lesions have a shorter survival than those of low-grade). In patients with advanced stage disease, the size of residual disease after surgery correlates most clearly with survival.36 The rapidity with which disease regresses during chemotherapy also correlates with survival. A short apparent half-life of the serum tumor marker CA 125 has correlated with improved survival in more than a dozen studies. Normalization of CA 125 by the third course of chemotherapy has been associated with a favorable prognosis.

Several biologic factors have been correlated with prognosis in epithelial ovarian cancer. Using flow cytometry, Friedlander and others have shown that ovarian cancers are commonly aneuploid and that a correlation exists between FIGO stage and ploidy, (low-stage cancers tend to be diploid and high-stage tumors tend to be aneuploid). Patients with diploid tumors have a significantly longer median survival than those with aneuploid tumors: 5 years versus 1 year, respectively. Multivariate analyses have demonstrated that ploidy is an independent prognostic variable and one of the most significant predictors of survival. Flow cytometric analysis also provides data on the cell cycle, and the proliferation fraction (S phase) determined by this technique has correlated with prognosis in some studies. More recent reports utilizing comparative genomic hybridization suggest that copy number abnormalities for chromosome segments also have prognostic significance.

Most sporadic ovarian carcinomas evolve from a single clone of cells. When primary cancers and metastases have been compared, more than 90% share the same patterns of loss of heterozygosity, inactivation of the same X chromosome and, when present, the same mutations in p53. Ovarian cancers can metastasize by multiple routes. Like other epithelial neoplasms, ovarian cancers can spread through lymphatics to the level of the renal hylus and can also spread hematogenously. Most frequently, however, ovarian cancer spreads over the surface of the peritoneum, studding the serosal surface of the bowel and abdominal wall and ultimately producing intestinal obstruction. Ascites formation results from increased leakage of proteinaceous fluid from capillaries under the influence of VEGF/VPF produced by ovarian cancers and from inhibition of fluid outflow through diaphragmatic lymphatics that have been blocked by metastatic disease. Studies of the immunobiology of the peritoneal cavity suggest that it may function as an immunoprivileged site, with elevated levels of suppressive molecules and growth factors.