Molecular abnormalities in ovarian cancer subtypes other than high-grade serous carcinoma

Abstract

Ovarian cancer is the fifth leading cause of cancer death in women in North America, and approximately two-thirds of cases of ovarian cancer are of high-grade serous type. The remaining cases are comprised of a mix of different tumor types (e.g., endometrioid, clear cell, mucinous, etc.), with no single tumor type accounting for more than 10% of ovarian cancer cases. These tumor types can be reproducibly diagnosed, and each features distinct underlying molecular events during oncogenesis, with a characteristic natural history and response rate to conventional cytotoxic chemotherapy. In this review the molecular abnormalities present in the more common non-high-grade serous subtypes of ovarian cancer will be presented. Development of targeted therapies for these tumor types will require understanding of the genetic basis of each tumor type, and may lead to subtype-specific therapy.

Figure 1

Ovarian carcinoma of endometrioid type (a). Immunostaining for beta-catenin shows both nuclear and membranous localization within the tumor cells (b).

Figure 2

HER2 immunostaining of a mucinous carcinoma shows diffuse membranous positivity. This was associated with high-level HER2 amplification on FISH analysis.

Figure 3

Results of sequencing of the transcriptome of a granulosa cell tumor, showing sequence from the FOXL2 gene (a). At nucleotide 402, both G and C were identified, indicating that this tumor was hemizygous for the 402C->G mutation charateristic of adult-type granulosa tumor. Granulosa tumor cell nuclei show high-level expression of the FOXL2 protein by immunostaining (b), in association with this mutation.