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 esoph ageal squamous-cell carcinoma specimens from patients who had undergon e curative resection. Mutations in the p53 gene within exons 5 to 8 we re 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 gen es 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 inact ivation of the p53 gene may contribute to the progression of this tumo r. (C) 1994 Wiley-Liss, Inc.