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Microsatellite Instability Is Associated with Tumors That Characterize the Hereditary Non-Polyposis Colorectal Carcinoma Syndrome¹

Department of Medical Genetics, P. O. Box 21, Haartmaninkatu 3, SF-00014 University of Helsinki, Finland [P. P., L. A. A., L. P., M. N-L., A. d. l. C.]; The Norwegian Radium Hospital, Departments of Genetics and Pathology, Institute for Cancer Research, Montebello, 0310 Oslo, Norway [R. A. L., R. H., A. B., A-L. B.]; Unit of Genetics—IPATIMUP, Medical Faculty of Porto, Hospital S. Joao, P-4200 Porto, Portugal [R. S., L. D.]; and Department of Toxicology, National Institute of Occupational Health, 0033 Oslo, Norway [D. R., A. H.].

Microsatellite instability implying multiple replication errors (RER+ phenotype) characterizes a proportion of colorectal carcinomas, particularly those from patients with the hereditary non-polyposis colorectal carcinoma syndrome. We studied the incidence of microsatellite instability in more than 500 sporadic tumors representing 6 different types of cancer. Apart from colorectal carcinoma [see the paper by Lothe et al. (Cancer Res., 53: 5849–5852, 1993)] the RER+ phenotype was found in 18% (6 of 33) of gastric carcinomas and 22% (4 of 18) of endometrial carcinomas. In contrast, no evidence of this abnormality was detected in cancers of the lung (N = 85), breast (N = 84), and testis (N = 86). Importantly, the first three cancers, as opposed to the latter three, are characteristic of the hereditary non-polyposis colorectal carcinoma syndrome. These findings suggest that the cancers belonging to the hereditary non-polyposis colorectal carcinoma tumor spectrum may have essential pathogenetic steps in common, including a tendency to multiple replication errors.

¹ Aided by grants from the Academy of Finland, the Finnish Cancer Society, the Sigrid Juselius Foundation, the Norwegian Research Council for Science and Humanities, and the Norwegian Cancer Society. Part of this study was done at the Folkhälsan Institute of Genetics.

² To whom requests for reprints should be addressed.

Received 10/ 9/93. Accepted 11/ 2/93.

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