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p53 Tumor Suppressor Gene Mutation in Early Esophageal Precancerous Lesions and Carcinoma among High-Risk Populations in Henan, China¹

Laboratory for Cancer Research, College of Pharmacy, Rutgers University, Piscataway, New Jersey 08855 [H. G., L-D. W., Q. Z., T-Y. H., J-Y. H., C. S. Y.], and Henan Institute of Medical Sciences, Henan Medical University, Zhengzhou 450052, China [L-D. W., Q. Z.]

To understand whether p53 gene mutation is an early or late event in esophageal carcinogenesis, biopsy samples of esophageal epithelium from symptom-free subjects in a high incidence area, Huixian county of Henan Province, China, were analyzed. Mutations in exons 5, 6, 7, and 8 of p53 were analyzed by single-strand conformation polymorphism analysis and DNA sequencing. Among the 37 biopsy samples showing accumulation of p53 protein in immunohistochemical staining, missense mutations of p53 gene were detected in 1 of 3 samples with normal epithelia, 3 of 23 samples with basal cell hyperplasia, and 4 of 11 samples with dysplasia. All mutations occurred at exon 5 with 3 at codon 175, 2 at codon 176, and 1 each at codons 159, 135, and codon 132. Of the 8 mutations, there were 3 G to A transitions and 3 G to T transversions. To understand the mutation spectrum and possible causative factors of esophageal cancer in this area, surgically resected human primary esophageal carcinomas from Linxian county were analyzed for p53 gene mutations in exons 5, 6, 7, and 8. Mutations were detected in 16 of 29 samples (55%). Twelve samples contained different missense point mutations, with 75% transitions (7 G to A and 2 A to G) and 25% transversions (2 G to T and 1 G to C). Most of the mutations were located at either exon 5 or exon 7. A deletion and an insertion of nucleotides leading to frame-shift mutations were detected in each of two other samples. The results demonstrate that p53 protein accumulation and gene mutation may occur at very early stages of esophageal carcinogenesis. In carcinomas, there was a higher frequency of p53 gene mutations, which accounts for most of the cases with p53 protein accumulation.

¹ This work was supported by NIH Grant CA37037 and National Institute of Environmental Health Sciences Center Grant ES05022.

² To whom requests for reprints should be addressed, at Laboratory for Cancer Research, College of Pharmacy, Rutgers University, Piscataway, NJ 08855.

Received 3/31/94. Accepted 6/13/94.

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