Aberrations of tumor-suppressor genes (p53, apc, mcc and Rb) in esophageal squamous-cell carcinoma.
Loss of heterozygosity at 4 tumor-suppressor gene loci (p53, apc, mcc and Rb) was investigated using polymerase chain reactions, in 49 esophageal squamous-cell carcinoma specimens from patients who had undergone curative resection. Mutations in the p53 gene within exons 5 to 8 were also examined. LOH was detected in 9 (43%) of 21 p53 genes, 16 (55%) of 29 apc genes, 10 (48%) of 21 mcc genes, and 13 (52%) of 25 Rb genes for which heterozygosity could be determined. Mutations in the p53 gene were detected in 18 (36%) of 49 cases and were significantly more frequent in stage-III tumors and in tumors exhibiting DNA aneuploidy. In 5 cases where heterozygosity could be determined for all the loci, all had 2 or more aberrations. Additionally, a heterozygous deletion of p53 gene was associated with a mutation of the remaining allele in 8 (89%) of 9 cases. Short-term relapse within 3 to 12 months occurred significantly more frequently in patients having tumors with both p53 aberrations (p < 0.05). Thus, aberration of tumor-suppressor genes was a frequent occurrence in esophageal squamous-cell carcinoma and inactivation of the p53 gene may contribute to the progression of this tumor.
Maesawa
C
C
Department of Pathology, Iwate Medical University School of Medicine, Uchimaru, Japan.
Tamura
G
G
Suzuki
Y
Y
Ogasawara
S
S
Ishida
K
K
Saito
K
K
Satodate
R
R
D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002869:Chromosome Aberrations; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D011003:Ploidies; D016133:Polymerase Chain Reaction; D011379:Prognosis