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. © Wiley‐Liss, Inc.