title: Genetics of synchronous uterine and ovarian endometrioid carcinoma: combined analyses of loss of heterozygosity, PTEN mutation, and microsatellite instability.
abstract: Synchronous development of carcinomas in the endometrium and ovaries is a fairly common phenomenon, but distinction of a single clonal tumor with metastasis from 2 independent primary tumors may present diagnostic problems. To determine clonality and the occurrence of progression, we microdissected multiple foci from 17 cases of synchronous endometrioid carcinomas and studied loss of heterozygosity (LOH), microsatellite instability (MI), and PTEN mutations. In 14 of the 17 cases, genetic alterations were either homogeneous or found in only some of the foci. LOH was detected for 10q (4 cases), 17p (2 cases), and 2p, 5q, 6q, 9p, 11q, 13q, and 16q (1 case each). Four cases had the MI phenotype with discordant MI patterns between both tumor sites, thus indicating a biclonal or triple clonal process. In 3 of 6 cases with PTEN mutations, identical mutations in both tumor sites indicated a single clonal neoplasm. Altogether, 14 synchronous tumors were genetically diagnosed as follows: single clonal tumor, characterized by concordant genetic alterations in both tumor sites, including identical LOH, identical PTEN mutations, and/or identical sporadic allelic instability patterns (4 cases); single clonal tumor with genetic progression, homogeneous LOH or identical PTEN mutations in both tumor sites and progressive LOH in ovarian metastatic foci (2 cases); and double (7 cases) or triple clonal tumors (1 case), determined by discordant PTEN mutations, heterogeneous LOH, and/or discordant MI patterns. Thus, 35% of synchronous tumors were monoclonal, 47% were polyclonal, and 18% were undetermined. The favorable prognosis of synchronous endometrioid carcinomas may be due to the occurrence of PTEN mutations in both independent and metastatic tumors, the MI-positive independent primary tumors, and the low frequency of LOH.
authors.affiliation: Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Fujii
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Manabu
authors.initials: M
authors.lastname: Yoshida
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Furugen
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takagaki
authors.forename: Keiichi
authors.initials: K
authors.lastname: Iwabuchi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Nakata
authors.forename: Yoshitake
authors.initials: Y
authors.lastname: Takagi
authors.forename: Takuya
authors.initials: T
authors.lastname: Moriya
authors.forename: Naomi
authors.initials: N
authors.lastname: Ohtsuji
authors.forename: Mareki
authors.initials: M
authors.lastname: Ohtsuji
authors.forename: Sachiko
authors.initials: S
authors.lastname: Hirose
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Shirai
mesh_terms: D000328:Adult; D002999:Clone Cells; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis / Q000175:diagnosis / Q000235:genetics; D009378:Neoplasms, Multiple Primary / Q000175:diagnosis / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics*; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D014594:Uterine Neoplasms / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human