Summary
p53 gene alterations in ten gastric adenomas and one carcinoma arising in an adenoma were analyzed by deoxynucleotide sequencing. Three (30%) of the ten gastric adenomas had p53 gene mutations, one adenoma showing a frameshift mutation and two others showing silent mutations. In addition, two missense mutations occurred in the carcinoma arising in an adenoma. Histologically, the adenomas containing silent mutations revealed moderate dysplasia. Immunoreactivity to p53 protein was also examined in 61 gastric adnomas, 19 carcinomas arising in adenomas and 48 early well-differentiated adenocarcinomas of the stomach (these included the tumors analyzed by deoxynucleotide sequencing). No staining for p53 was seen in the pure adenomas, but positive immunoreactivity was observed in 27% of the adenocarcinomas and 10.5% of the carcinomas arising in adenomas. These results suggest that p53 gene mutation is an early event in gastric carcinogenesis and missense mutation may play a crucial role in the conversion from adenoma to adenocarcinoma.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ayhan A, Yasui W, Yokozaki H, Ito H, Tahara E (1992) Genetic abnormalities and expression of p53 in human colon carcinomas. Int J Oncol 1:431–437
Baker SJ, Preisinger AC, Jessup JM, Paraskeva C, Markowitz S, Willson JKV, Hamilton S, Vogelstein B (1990) p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis. Cancer Res 50:7717–7722
Bressac B, Kew M, Wands J, Ozturk M (1991) Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa. Nature 350:429–431
Finlay CA, Hinds PW, Tan TH, Eliyahu D, Oren M, Levine AJ (1988) Activating mutations for transformation by p53 produce a gene product that forms an hsc70-p53 complex with an altered half-life. Mol Cell Biol 8:531–539
Frankel RH, Bayona W, Koslow M, Newcomb EW (1992) p53 mutations in human malignant gliomas: comparison of loss of heterozygosity with mutation frequency. Cancer Res 52:1427–1433
Gaidano G, Ballerini P, Gong JZ, Inghirami G, Neri A, Newcomb EW, Magrath IT, Knowles DM, Dalla-Favera R (1991) p53 mutations in human lymphoid malignancies: association with Burkitt lymphoma and chronic lymphocytic leukemia. Proc Natl Acad Sci USA 88:5413–5417
Harris CC (1990) Chemical and physical carcinogens: advances and perspectives for the 1990. Cancer Res 51 [Suppl]:5011s-5086s
Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) p53 mutations in human cancers. Science 253:49–53
Horii A, Nakatsuru S, Miyoshi Y, Ichii S, Nagase H, Kato Y, Yanagisawa A, Nakamura Y (1992) The APC gene, responsible for familial adenomatous polyposis, is mutated in human gastric cancer. Cancer Res 52:3231–3233
Hsu IC, Metcalf RA, Sun T, Welsh JA, Wang NJ, Harris CC (1991) Mutational hotspot in the p53 gene in human hepatocellular carcinomas. Nature 350:427–428
Hsu SM, Raine L, Fanger H (1981) A comparative study of the peroxidase anti-peroxidase method and avidin-biotin-complex method for studying polypeptide hormones with radioimmunoassay antibodies. Am J Clin Pathol 75:734–738
Ito H, Hata J, Yokozaki H, Nakatani H, Oda N, Tahara E (1986) Tubular adenoma of the human stomach. Cancer 58:2264–2272
Lehman TA, Bennett WP, Metcalf RA, Welsh JA, Ecker J, Modali RV, Ullrich S, Romano JW, Appella E, Testra JR, Gerwin BI, Harris CC (1991) p53 mutations,ras mutations, and p53heat shock 70 protein complexes in human lung carcinoma cell lines. Cancer Res 51:4090–4096
Mattar R, Yokozaki H, Yasui W, Ito H, Tahara E (1992) p53 gene mutations in gastric cancer cell lines. Oncology 11:7–12
Mitsudomi T, Steinberg SM, Nau MM, Carbone D, D’Amico D, Bodner S, Oie HK, Linnoila RI, Mulshine JL, Minna JD, Gazdar AF (1992) p53 gene mutations in non-small-cell lung cancer cell lines and their correlation with the presence of ras mutations and clinical fuatures. Oncogene 7:171–180
Morson BC, Dawson IMP (1972) Adenomas and the adenomacarcinoma sequence. In: Morson BC, Dawson IMP (eds) Gastrointestinal pathology. Blackwell, Oxford, pp 615–647
Nigro JM, Baker SJ, Preisinger AC, Jessup JM, Hostetter R, Cleary K, Bigner SH, Davidson N, Baylin S, Devilee P, Glover T, Collins FS, Weston A, Modali R, Harris CC, Vogelstein B (1989) Mutations in the p53 gene occur in diverse human tumor types. Nature 342:705–708
Sano T, Tsujino T, Yoshida K, Nakayama H, Haruma K, Ito H, Nakamura Y, Kajiyama G, Tahara E (1991) Frequent loss of heterozygosity on chromosomes 1q, 5q, and 17p in human gastric carcinomas. Cancer Res 51:2926–2931
Tahara E (1993) Molecular mechanism of stomach carcinogenesis. J Cancer Res Clin Oncol 119 (in press)
Takahashi T, Takahashi T, Suzuki H, Hida T, Sekido Y, Ariyoshi Y, Ueda R (1991) The p53 gene is very frequently mutated in small-cell lung cancer with a distinct nucleotide substitution pattern. Oncogene 6:1775–1778
Todo H, Haruma K, Yoshihara M, Ogasawara H, Suzuki T, Sumii K, Kajiyama G, Kunita T, Hidaka T, Tahara E (1990) Clinical management of group III lesion (in Japanese). Gastroenterol Endosc 32:1133–1139
Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AMM, Bos JL (1988) Genetic alterations during colorectal tumor development. N Engl J Med 319:525–532
Yokozaki H, Kuniyasu H, Kitadai Y, Nishimura K, Todo H, Ayhan A, Yasui W, Ito H, Tahara E (1992) p53 point mutations in primary human gastric carcinomas. J Cancer Res Clin Oncol 119:67–70
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tohdo, H., Yokozaki, H., Haruma, K. et al. p53 gene mutations in gastric adenomas. Virchows Archiv B Cell Pathol 63, 191–195 (1993). https://doi.org/10.1007/BF02899260
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02899260