Molecular abnormalities in ovarian carcinoma: clinical, morphological and therapeutic correlates - open access

 open access (note: 2012 posted as abstract only)

Introduction

In the 2002 World Health Organization (WHO) Blue Book[1] a wide range of ovarian carcinoma subtypes are described, but the reality of the era when the book was written was that ovarian carcinoma was managed as if it were a single disease. Since then, there have been significant advances in our understanding of the molecular alterations in ovarian carcinoma, with refinement of the diagnostic criteria for ovarian carcinoma subtypes, which will be reflected in the forthcoming update to the WHO classification system. It is no longer appropriate to consider ovarian carcinoma to be a single disease. While a simplified classification of ovarian carcinoma into Type I and Type II tumours has been suggested,[2, 3] this system perpetuates the earlier error of lumping together unrelated tumour types (e.g. mucinous and clear cell); this has had the effect of holding back progress towards subtype specific therapy, and is to be avoided. Some valid points are made within this classification system, in that the Type I (low-grade) tumours (including low-grade serous, low-grade endometrioid, clear cell and mucinous carcinomas) generally harbour somatic mutations in genes encoding specific protein kinases and other signalling molecules, creating opportunities for targeted therapy, while the Type II (high-grade serous) tumours do not have frequent/recurrent mutations in specific oncogenes. None the less, there are consistent differences between the tumour subtypes lumped together as Type I and these subtypes are best considered as specific tumour types. It is worth noting that high-grade serous carcinomas account for 70% of all ovarian carcinomas and are responsible for 90% of ovarian cancer deaths[4, 5]; significantly lowering overall morbidity and mortality from ovarian carcinoma will therefore necessarily have to focus on this subtype.

This review will discuss recent advances in understanding the molecular pathology and pathogenesis of ovarian carcinoma, considering each of the five subtypes. Their respective responses to currently available treatments will be discussed briefly, along with emerging subtype-specific therapeutic agents..........