This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kikuchi-Yanoshita, R. Articles by Miyaki, M. Search for Related Content PubMed PubMed Citation Articles by Kikuchi-Yanoshita, R. Articles by Miyaki, M.

Genetic Changes of Both p53 Alleles Associated with the Conversion from Colorectal Adenoma to Early Carcinoma in Familial Adenomatous Polyposis and Non-Familial Adenomatous Polyposis Patients¹

Departments of Biochemistry [R. K-Y., M. Kon., S. I., M. S., K. T., M. M.] and Clinical Genetics, [H. S.], The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome; Department of Pathology and Surgery, The Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome [Y. M., H. I., M. F., M. Koi., T. M.]; and Department of Surgery, Tokyo Medical and Dental University, Yushima [H. F., T. I.], Bunkyo-ku, Tokyo, 113, Japan

Mutation and loss of heterozygosity (LOH) in the p53 gene were analyzed in 274 colorectal tumors of 4 histopathological grades. Among 160 tumors from 40 familial adenomatous polyposis patients, none of 58 adenomas with moderate dysplasia had p53 mutations, whereas 8% (3 of 37) of severe adenomas, 15% (6 of 40) of intramucosal carcinomas, and 40% (10 of 25) of invasive carcinomas had p53 mutations. Only 3% (1 of 33) of severe adenomas showed both mutation and LOH, while 25% (6 of 24) of intramucosal carcinomas and 40% (10 of 25) of invasive carcinomas had both mutation and LOH. All intramucosal and invasive carcinomas that had mutations lost the other allele of the p53 gene. In 114 tumors from 86 non-familial adenomatous polyposis patients, similar results were obtained; no adenoma showed both mutation and LOH, but both alterations occurred in intramucosal and invasive carcinomas.

As regards specificity in 56 mutations detected in the present study, the frequently affected codons were codons 175, 238, 245, 248, 273, and 282, 4 of these amino acids being arginine, and 72% (39 of 54) of all mutations were GC to AT transition. Although expression into p53 polyadenylated RNA was high in every invasive carcinoma irrespective of the presence of mutation or LOH, there was a correlation between mutation and protein level; immunostaining of p53 protein was negative in almost all adenomas, but it was positive in 86% of invasive carcinomas exhibiting p53 mutation.

These data suggest that genetic changes on both alleles of the p53 gene through mutation and LOH, which result in abnormal protein accumulation, are involved in the conversion of adenoma to early carcinoma. Also, carcinoma cells with p53 mutations existing within adenoma tissues are detectable by immunostaining, even in formalin-fixed, paraffin-embedded specimens.

¹ This work was supported in part by Grants-in-Aid for Cancer Research from the Ministry of Education, Science and Culture of Japan and from the Ministry of Health and Welfare of Japan.

² To whom requests for reprints should be addressed.

Received 12/26/91. Accepted 5/ 6/92.

This article has been cited by other articles:

				J. G. Einspahr, M. E. Martinez, R. Jiang, C.-H. Hsu, A. K. Bhattacharrya, D. J. Ahnen, E. T. Jacobs, P. S. Houlihan, C. R. Webb, D. S. Alberts, et al. Associations of Ki-ras Proto-oncogene Mutation and p53 Gene Overexpression in Sporadic Colorectal Adenomas with Demographic and Clinicopathologic Characteristics. Cancer Epidemiol. Biomarkers Prev., August 1, 2006; 15(8): 1443 - 1450. [Abstract] [Full Text] [PDF]

				B. Diergaarde, A. Vrieling, A. A. van Kraats, G. N.P. van Muijen, F. J. Kok, and E. Kampman Cigarette smoking and genetic alterations in sporadic colon carcinomas Carcinogenesis, March 1, 2003; 24(3): 565 - 571. [Abstract] [Full Text] [PDF]

				M Miyaki, T Iijima, M Ohue, Y Kita, T Hishima, T Kuroki, T Iwama, and T Mori A novel case with germline p53 gene mutation having concurrent multiple primary colon tumours Gut, February 1, 2003; 52(2): 304 - 306. [Abstract] [Full Text] [PDF]

				T. Sugai, W. Habano, N. Uesugi, Y.-F. Jiao, S.-i. Nakamura, K. Sato, T. Chiba, and M. Ishii Molecular Validation of the Modified Vienna Classification of Colorectal Tumors J. Mol. Diagn., November 1, 2002; 4(4): 191 - 200. [Abstract] [Full Text] [PDF]

				M. Miyaki, T. Iijima, R. Ishii, Y. Kita, M. Koike, T. Kuroki, and T. Mori Increased Frequency of p53 Mutation in Sporadic Colorectal Cancer from Cigarette Smokers Jpn. J. Clin. Oncol., June 1, 2002; 32(6): 196 - 201. [Abstract] [Full Text] [PDF]

				X P Hao, I M Frayling, J G Sgouros, M Q Du, T C Willcocks, I C Talbot, and I P M Tomlinson The spectrum of p53 mutations in colorectal adenomas differs from that in colorectal carcinomas Gut, June 1, 2002; 50(6): 834 - 839. [Abstract] [Full Text] [PDF]

				E. Sadot, B. Geiger, M. Oren, and A. Ben-Ze'ev Down-Regulation of {beta}-Catenin by Activated p53 Mol. Cell. Biol., October 15, 2001; 21(20): 6768 - 6781. [Abstract] [Full Text] [PDF]

				Y. Maniwa, M. Yoshimura, C. Obayashi, M. Inaba, K. Kiyooka, M. Kanki, and Y. Okita Association of p53 Gene Mutation and Telomerase Activity in Resectable Non-Small Cell Lung Cancer Chest, August 1, 2001; 120(2): 589 - 594. [Abstract] [Full Text] [PDF]

				M. Miyaki, T. Iijima, K. Hosono, R. Ishii, M. Yasuno, T. Mori, M. Toi, T. Hishima, N. Shitara, K. Tamura, et al. Somatic Mutations of LKB1 and {beta}-Catenin Genes in Gastrointestinal Polyps from Patients with Peutz-Jeghers Syndrome Cancer Res., November 1, 2000; 60(22): 6311 - 6313. [Abstract] [Full Text]

				K Shitoh, F Konishi, M Miyaki, T Iijima, T Furukawa, T Tsukamoto, and H Nagai Pathogenesis of non-familial colorectal carcinomas with high microsatellite instability J. Clin. Pathol., November 1, 2000; 53(11): 841 - 845. [Abstract] [Full Text] [PDF]