Ovarian Cancer-Challenges and Innovations

Dualistic Typing of Epithelial Ovarian Cancers: Emerging Paradigms for Oncogenic Progression and Cancer Treatment

Author(s): D. Stave Kohtz

Pp: 106-129 (24)

DOI: 10.2174/9789811421860119010007


Dualistic classifications assign tumors arising from one tissue into two broad types based on differences in histology or grade, growth parameters (e.g., hormone dependence or independence), prognosis, or expression of specific markers. Genomic analyses have allowed a more mechanistic expression of dualistic classification, so that tumor types may be founded on functional differences in the genetics of their development. This review considers the dualistic model of ovarian cancer, which is based primarily on whether or not mutations in the TP53 gene appear in the chronology of tumor progression. Type I ovarian cancers generally do not display mutations in the TP53 gene, and, according to several criteria, they have developed in the context of a relatively stable genome. In contrast, Type II ovarian cancers develop mutations in the TP53 gene early in tumorigenesis, and the resulting genome destabilization becomes a primary driver in tumorigenesis. Type I ovarian cancers generally are of lower grade and display a less malignant phenotype than Type II ovarian cancers, despite the better response of Type II ovarian cancers to certain chemotherapeutic regimens. Some reports have shown that mutation of TP53 can occur, albeit rarely late in a putative Type I progression, giving rise to an ovarian cancer with growth and survival properties similar to a Type II cancer. Future work should apply principles of dualistic cancer lineages acquired from ovarian and some other cancers (e.g., sporadic and inflammatory bowel disease-associated colorectal cancer) to produce a unified model applicable to the prognostication and development of therapeutics for all cancers.

Keywords: Dualistic tumor classification, Genomic destabilization, Type I ovarian cancer, Type II ovarian cancer, TP53, Tumor progression.

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