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 prognostic value of both the deletion of candidate tumor suppressor genes and the DNA content in colorectal carcinoma specimens.


METHODS
A prospective study was initiated in 1988, into which 104 patients from the Brooklyn VA Medical Center were accrued through March 1992. DNA restriction endonuclease digests, obtained by the Southern blot technique, were examined for allelic deletions by cDNA probes pnm23-H1 (17q21) YNZ 22.1 (17p13), and p15-65 (18q21). DNA content was measured by image analysis 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 patients without nm23-H1 deletions (relative risk [RR], 3.89; 95% confidence interval [CI], 1.39, 10.89). This connection was even stronger after adjustment for TNM stage and site of primary tumor (RR, 5.27; 95% CI, 1.67, 16.68). No significant association of 17p or 18q deletions or ploidy with either distant metastases or overall survival was noted. In multivariate analysis, clinicopathologic variables associated with decreased survival included intracellular mucin production, nuclear grade, TNM stage, and nerve invasion.


CONCLUSIONS
A combination of clinicopathologic and molecular biologic variables may identify patients at high risk for death from disseminated colorectal carcinoma.
Cohn
K H
KH
Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.
Ornstein
D L
DL
Wang
F
F
LaPaix
F D
FD
Phipps
K
K
Edelsberg
C
C
Zuna
R
R
Mott
L A
LA
Dunn
J L
JL
D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D003110:Colonic Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006801:Humans; D008297:Male; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009367:Neoplasm Staging; D009701:Nucleoside-Diphosphate Kinase; D011446:Prospective Studies; D012004:Rectal Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D054778:NM23 Nucleoside Diphosphate Kinases; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins