title: Genetic pathways of multiple esophageal squamous cell carcinomas.
abstract: Whether multiple esophageal squamous cell carcinomas (SCCs) in a patient develop through an identical genetic pathway is still unclear. We examined multiple esophageal SCCs for alterations of p53, p16, IRF and mitochondrial DNA (mtDNA) and microsatellite instability (MSI). Thirty patients with multiple superficial esophageal SCCs, 23 with double lesions and 7 with triple lesions, were enrolled. Loss of heterozygosity (LOH) of p53 (TP53), p16 (D9S171), IRF (IRF) and other microsatellite loci including D1S191, D17S858, D18S58 and D18S61 of the tumors was examined by microsatellite assay. Mutations of p16 and mtDNA were examined with PCR single-strand conformation polymorphism (SSCP) analysis. LOH of p53, p16 and IRF were detected in 16 of 50 (32%), 5 of 38 (13%) and 5 of 48 (10%) tumors, respectively. Mutations of p16 were detected in 4 of 67 (6%) tumors. Six of 67 (9%) tumors had mtDNA alterations and none of the tumors showed high-frequency MSI. All 30 patients showed one or more gene alterations in one or more genetic loci. Discordant genetic patterns among individual lesions within a patient were observed in 28 of the 30 (93%) patients. The most discordant locus was TP53, present in 11 of 29 (38%) informative cases, followed by D18S61, present in 11 of 30 (37%) informative cases. These results suggest that the genetic pathways of multiple esophageal SCCs may differ even within the same patient.
authors.affiliation: Department of Gastroenterology and Metabolism, Hiroshima University Hospital, Health Service Center, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Takayasu
authors.initials: T
authors.lastname: Kuwabara
authors.forename: Toru
authors.initials: T
authors.lastname: Hiyama
authors.forename: Shinji
authors.initials: S
authors.lastname: Tanaka
authors.forename: Masaharu
authors.initials: M
authors.lastname: Yoshihara
authors.forename: Koji
authors.initials: K
authors.lastname: Arihiro
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004252:DNA Mutational Analysis; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019942:Genes, p16; D016158:Genes, p53; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics