Intratumoural cytogenetic heterogeneity of sporadic colorectal carcinomas suggests several pathways to liver metastasis

• Published in: The Journal of pathology 2010-07, Vol.221 (3), p.308-319
• Main Authors: Sayagués, José María, del Mar Abad, María, Melchor, Hermann Barquero, Gutiérrez, María Laura, González-González, María, Jensen, Evan, Bengoechea, Oscar, Fonseca, Emilio, Orfao, Alberto, Muñoz-Bellvis, Luís
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adenocarcinoma - secondary; Aged; Aged, 80 and over; Biological and medical sciences; chromosomal abnormalities; Chromosome 1; chromosome 17; chromosome 6; chromosome 7; chromosome 8; Chromosome Aberrations; Chromosomes; clonal evolution; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; DNA, Neoplasm - genetics; Female; Fluorescence in situ hybridization; Gastroenterology. Liver. Pancreas. Abdomen; histopathology; Humans; iFISH; In Situ Hybridization, Fluorescence; Interphase; Investigative techniques, diagnostic techniques (general aspects); Karyotypes; Karyotyping; Liver; liver metastases; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Liver Neoplasms - secondary; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Metastases; Middle Aged; Neoplasm Staging; Neoplastic Stem Cells - pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Probes; Risk factors; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.2712

Much has been learned about the chromosomal abnormalities of colorectal carcinomas but the cytogenetic relationship between the neoplastic clones present in primary versus metastatic tumour samples remains unclear. We analyse the frequency of abnormalities for 47 chromosome regions using the interphase fluorescence in situ hybridization technique in a group of 48 tumours, including 24 primary colorectal tumours and 24 paired liver metastases. All tumours showed complex karyotypes with numerical/structural abnormalities for seven or more different chromosomes/chromosome regions both in the primary tumours and in their paired metastases. Chromosome 8 was the most frequently altered (22/24 primary tumours), consistently showing del(8p22) and/or gains/amplification of 8q24, followed by abnormalities of the entire chromosome 7 (21/24 primary tumours) and of chromosomes 17p and 20q (20/24 primary tumours). Simultaneous staining for multiple chromosome probes revealed the presence of two or more tumour cell clones in 23/24 cases (46/48 tumour samples). Interestingly, the liver metastases typically contained tumour cell clones similar to those found in the primary tumours, suggesting the absence of selective selection of specific tumour clones. Despite this, additional chromosomal abnormalities were detected in 23/24 metastatic tumours, which preferentially consisted of del(17p13) and gains/amplification of 11q13 and 20q13; moreover, compared to primary tumours, metastases showed an increased number of abnormalities of chromosomes 1p, 7q, 8q, 13q, and 18q, and new chromosomal abnormalities involving chromosomes 6, 10q23, 14q32, 15q22, and 19q13. Owing to the high frequency of numerical abnormalities of the entire chromosome 7 and loss and/or gain/amplification of specific regions of chromosome 8, eg del(8p22) and/or gains/amplification of 8q24 in primary colorectal tumours with associated metastases, it is suggested that their assessment at diagnosis could be of great clinical utility for the identification of colorectal cancer patients at higher risk of developing liver metastases. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.