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Loss of Heterozygosity and DNA Aneuploidy in Colorectal Adenocarcinoma

From the Department of Surgery, Division of Colon & Rectal Surgery (J-KL, S-CC), and Department of Pathology (AF-YL), Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine (S-CC), National Yang-Ming University, Taipei, Taiwan; School of Medical Technology (Y-CY), College of Medicine, Institute of Epidemiology, College of Public Health; and Department of Laboratory Medicine (Y-CY), College of Medicine, National Taiwan University, Taipei, Taiwan.

Correspondence: Address correspondence and reprint requests to: Jen-Kou Lin, MD, PhD, Division of Colon & Rectal Surgery, Department of Surgery, Veterans General Hospital Taipei, No. 201, Sec. 2, Shih-Pai Rd., Taipei 11217, Taiwan, ROC; Fax: 886-2-287-57639; E-mail: jklin{at}vghtpe.gov.tw

Background: This study evaluated the relationship between DNA aneuploidy and loss of heterozygosity (LOH) at different genetic loci in colorectal adenocarcinoma.

Methods: A total of 112 patients with surgically removed colorectal adenocarcinoma in Taipei Veterans General Hospital from January 1999 to July 2001 were included in this study. The pattern of DNA ploidy was determined with DNA flow cytometry, and the LOH of various genetic loci was determined with fluorescence polymerase chain reaction and denaturing gradient gel electrophoresis. The relationship between DNA ploidy, LOH of various genetic loci, and clinicopathologic variables was analyzed with the ² test with Yates’ correction as well as by multivariate binary logistic regression analysis.

Results: Seventy-one (63.4%) of the 112 carcinomas had DNA aneuploidy. The DNA aneuploidy was not associated with any clinicopathologic variable. Ninety-one tumors (81.3%) exhibited LOH in at least one genetic locus. In the univariate analysis, the DNA aneuploidy was associated with LOH of Tp53-penta, D8S254, D5S346, and high-frequency LOH (P = .001, P = .016, P = .041, and P < .001, respectively). In the multivariate analysis, the most significant factor influencing DNA aneuploidy was D8S254, followed by Tp53-penta, high-frequency LOH, and D5S346.

Conclusions: DNA aneuploidy is strongly associated with LOH at specific genetic loci.

Key Words: Loss of heterozygosity • Aneuploidy • Microsatellite instability • Colorectal neoplasms • p53 • APC

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