Early events in the pathogenesis of epithelial ovarian cancer.
Ovarian carcinogenesis, as in most cancers, involves multiple genetic alterations. A great deal has been learned about proteins and pathways important in the early stages of malignant transformation and metastasis, as derived from studies of individual tumors, microarray data, animal models, and inherited disorders that confer susceptibility. However, a full understanding of the earliest recognizable events in epithelial ovarian carcinogenesis is limited by the lack of a well-defined premalignant state common to all ovarian subtypes and by the paucity of data from early-stage cancers. Evidence suggests that ovarian cancers can progress both through a stepwise mutation process (low-grade pathway) and through greater genetic instability that leads to rapid metastasis without an identifiable precursor lesion (high-grade pathway). In this review, we discuss many of the genetic and molecular disorders in each key process that is altered in cancer cells, and we present a model of ovarian pathogenesis that incorporates the role of tumor cell mutations and factors in the host microenvironment important to tumor initiation and progression.
Landen
Charles N
CN
Department of Gynecologic Oncology, University of Texas M.D. Anderson Cancer Center, 1155 Herman Pressler, Unit 1362, Houston, TX 77030, USA.
Birrer
Michael J
MJ
Sood
Anil K
AK
D000818:Animals; D002277:Carcinoma / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D046228:Microarray Analysis; D009154:Mutation; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction
D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone