Gastroenterology

Gastroenterology

Volume 114, Issue 6, June 1998, Pages 1188-1195
Gastroenterology

Alimentary Tract
Prognostic significance of allelic loss at chromosome 18q21 for stage II colorectal cancer,☆☆

https://doi.org/10.1016/S0016-5085(98)70424-XGet rights and content

Abstract

Background & Aims: Allelic loss of a portion of chromosome 18q and lack of expression of deleted in colorectal cancer (DCC) protein has been reported as an adverse prognostic indicator for stage II (i.e., Dukes' B2) colorectal cancer. Our aim was to assess whether the DCC gene locus was responsible. Methods: We amplified five DNA microsatellite markers located on chromosome 18q21 surrounding or within the DCC gene locus, including a DCC intragenic (TA)n microsatellite, from DNA microdissected and isolated from paraffin-embedded, formalin-fixed specimens of 70 patients with stage II colorectal cancer. Epidemiological and survival data were blinded from the microsatellite analysis to avoid bias. Results: The average follow-up time was 63.3 months for all patients. Eleven patients died of colorectal cancer by the end of the study. Loss of heterozygosity of 18q21 was present in 30 of 70 (43%) tumors. After adjustment for all other evaluated factors, 18q21 allelic loss was not a predictor of survival (hazard ratio, 1.17; 95% confidence interval, 0.27–5.10; P = 0.84). Conclusions: Loss of heterozygosity of 18q21 does not seem to predict a survival disadvantage in stage II colorectal cancer in our patient population, and its proposed use as a prognosticator of survival or chemotherapy stratification marker for stage II tumors is not substantiated.

GASTROENTEROLOGY 1998;114:1188-1195

Section snippets

Patient selection and data collection

Seventy patients with stage II colorectal cancer (Dukes' B2 lesions; invasive through the muscularis propria but lymph node negative) for whom pathology slides were available were identified consecutively from the tumor registry at Ohio State University from 1984 to 1988 and the tumor registry at the University of Michigan from 1984 to 1989. This period was chosen because postoperative adjuvant chemotherapy was not administered routinely to patients commonly at these institutions until after

Results

We analyzed 70 stage II colorectal tumors in a blinded fashion for allelic loss at five 18q21 DNA microsatellite markers that are tightly linked to the DCC gene locus, including an intragenic microsatellite located within the DCC gene (18q DCC-TA) (Figure 1).

. Genetic linkage map of microsatellite markers on chromosome 18q. Gene and microsatellite location and centimorgan distance along chromosome 18q were pooled from Genome Data Base,22 Genethon human genetic linkage map,33 and Eppert et al.13

Discussion

The purpose of this study was to validate in a blinded fashion whether allelic loss at chromosome 18q21 around and within the DCC gene is a significant prognostic indicator of survival in stage II colorectal cancer. In our patient population, we were unable to find an association between 18q21 allelic loss and survival by univariate analysis and multivariate analysis.

Our conclusions differ greatly from those of Jen et al.7 Comparison with their study shows a similar number of stage II patients

Acknowledgements

The authors thank Sajeev Cherian for assistance.

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  • Cited by (0)

    Supported by National Institutes of Health grants DK02433, CA72851, and CA57716; the Robert Wood Johnson Foundation; the “V” Foundation for Cancer Research; and the Veterans Administration Research Service.

    ☆☆

    Address requests for reprints to: John M. Carethers, M.D., Department of Medicine 0688, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0688. e-mail: [email protected]; fax: (619) 822-0301.

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