THE SIGNIFICANCE OF ALLELIC DELETIONS AND ANEUPLOIDY IN COLORECTAL-CARCINOMA - RESULTS OF A 5-YEAR FOLLOW-UP-STUDY

BACKGROUND. A prospective study was initiated to analyze the prognosti c value of both the deletion of candidate tumor suppressor genes and t he DNA content in colorectal carcinoma specimens. METHODS. A prospecti ve study was initiated in 1988, into which 104 patients from the Brook lyn VA Medical Center were accrued through March 1992. DNA restriction endonuclease digests, obtained by the Southern blot technique, were e xamined for allelic deletions by cDNA probes pnm23-H1 (17q21) YNZ 22.1 (17p13), and p15-65 (18q21). DNA content was measured by image analys is cytometry of Feulgen-stained tumor imprints. Median follow-up was 5 .5 years (range, 4-8.5 years). RESULTS. Patients with nm23-H1 allelic deletions were 3 times as likely to develop distant metastases as pati ents without mm23-H1 deletions (relative risk [RR], 3.89; 95% confiden ce interval [CI], 1.39, 10.89). This connection was even stronger afte r adjustment for TNM stage and site of primary tumor (RR, 5.27; 95% Ct , 1.67, 16.68). No significant association of 17p or 18q deletions or ploidy with either distant metastases or overall survival was noted. I n multivariate analysis, clinicopathologic variables associated with d ecreased survival included intracellular mucin production, nuclear gra de, TNM stage, and nerve invasion. CONCLUSIONS. A combination of clini copathologic and molecular biologic variables may identify patients at high risk for death from disseminated colorectal carcinoma. (C) 1997 American Cancer Society.