Basic–Alimentary TractColorectal adenoma to carcinoma progression follows multiple pathways of chromosomal instability☆,☆☆
Section snippets
Tumor material
A total of 194 tumor samples were studied, consisting of 66 nonprogressed adenomas (i.e., simple adenomas without invasion), 46 progressed adenomas (in which a focus of carcinoma already is present, also referred to as malignant polyps), of which both the adenoma part and the carcinoma part were analyzed separately; and 36 simple carcinomas. The samples were obtained from 93 patients, 41 female and 52 male. The mean age was 67 years (range, 40–91). Thirty patients had multiple tumors: 5 had
Comparative genomic hybridization results in relation to adenoma-carcinoma progression
Nineteen nonprogressed adenomas did not show any chromosomal abnormality. The remaining 47 nonprogressed adenoma cases showed few chromosomal aberrations (on average, 4.6). These aberrations showed a rather random distribution over the chromosomes, although there were more losses than gains (ratio of loss to gain, 2:7). The average number of chromosomal aberrations in the 46 progressed adenomas was 10.5, significantly higher than in the nonprogressed adenomas (P = 0.000) and similar to the
Discussion
Current genetic models of colorectal adenoma-carcinoma progression do not reflect the complexity of the disease. We compared genomewide chromosomal aberrations in nonprogressed adenomas to adenomas proven capable of progression toward malignancy. The present data, obtained from a cross-sectional study of a total of 194 tumor samples, revealed that gains at 8q23-qter, 13q14-31, and 20q13 and losses at 8p21-pter, 15q11-q21, 17p12-13, and 18q12-21 were strongly associated with advanced lesions,
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Address requests for reprints to: Gerrit Meijer, M.D., Ph.D., Department of Pathology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, the Netherlands. e-mail: [email protected]; fax: (31) 20-444-2964.
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Supported by the Dutch Cancer Society grants KWF97-1455 and ZONMW 28-1687, and Miur Oncology grant N.02.00273.ST97 (to W.G.).