title: Molecular pathogenesis of endometriosis-associated clear cell carcinoma of the ovary (review).
abstract: Epithelial ovarian cancer (EOC) is the leading cause of death in women with gynecological malignancies. Among EOC, clear cell carcinoma (CCC) and endometrioid adenocarcinoma (EAC) differ from the other histological types with respect to their clinical characteristics and carcinogenesis. Both tumor types are often associated with endometriosis. EAC is recently reported to be characterized by K-RAS activation and PTEN dysfunction. However, the molecular changes in CCC remain largely unknown. The aim of this review is to summarize the current knowledge on the molecular mechanisms involved in CCC tumorigenesis. The present article reviews the English language literature for biological, pathogenetic and pathophysiological studies on endometriosis-associated CCC of the ovary. Several recent studies of loss of heterozygosity (LOH), allelic loss, comparative genomic hybridization, mutation, methylation status, microarray gene-expression profiling and proteomics are discussed in the context of CCC biology. Retrograde menstruation or ovarian hemorrhage carries highly pro-oxidant factors, such as heme and iron, into the peritoneal cavity or ovarian endometrioma. A histologically normal ectopic endometrium bears genetic damages caused by iron-dependent oxidative stress. DNA damage or LOH caused by oxidative stress is a critical factor in the carcinogenic process. LOH studies have implicated the involvement of specific chromosomal regions (5q, 6q, 9p, 10q, 11q, 17q and 22q). Furthermore, the PTEN and APC (early event), p53, polo-like kinases, Emi1 and K-RAS (late event) genes may be involved in CCC carcinogenesis. The molecular pathology of CCC is heterogeneous and involves various putative precursor lesions and multiple pathways of development, possibly via genetic alteration by oxidative stress.
authors: Department of Obstetrics and Gynecology, Nara Medical University, Kashihara 634-8522, Japan. hirokoba@naramed-u.ac.jp
authors: Hiroshi
authors: H
authors: Kobayashi
authors: Hirotaka
authors: H
authors: Kajiwara
authors: Seiji
authors: S
authors: Kanayama
authors: Yoshihiko
authors: Y
authors: Yamada
authors: Naoto
authors: N
authors: Furukawa
authors: Taketoshi
authors: T
authors: Noguchi
authors: Shoji
authors: S
authors: Haruta
authors: Shozo
authors: S
authors: Yoshida
authors: Mariko
authors: M
authors: Sakata
authors: Toshiyuki
authors: T
authors: Sado
authors: Hidekazu
authors: H
authors: Oi
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000209:etiology*; D018797:Cell Cycle Proteins / Q000502:physiology; D004715:Endometriosis / Q000150:complications*; D044783:F-Box Proteins / Q000502:physiology; D005260:Female; D016147:Genes, Tumor Suppressor; D051539:Hepatocyte Nuclear Factor 1-beta / Q000502:physiology; D006801:Humans; D019656:Loss of Heterozygosity; D053842:Microsatellite Instability; D010051:Ovarian Neoplasms / Q000209:etiology*; D018384:Oxidative Stress; D011494:Protein Kinases / Q000502:physiology; D058570:TOR Serine-Threonine Kinases
chemical_list: D018797:Cell Cycle Proteins; D044783:F-Box Proteins; C498960:FBXO5 protein, human; D051539:Hepatocyte Nuclear Factor 1-beta; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases