Loss of heterozygosity at 3p23 is correlated with poor survival in patients with colorectal carcinoma.
BACKGROUND
Loss of heterozygosity (LOH) of chromosome 3p has been observed commonly in carcinomas of various tumor tissues, including colorectal carcinoma (CRC). Because there is no report analyzing 3p deletions in relation to patient prognosis in CRC, the authors investigated the prognostic value of LOH on 3p in 87 patients with sporadic CRC.


METHODS
DNA samples from tumor and nontumor tissues were amplified by using polymerase chain reaction (PCR) and were analyzed for LOH on 3p using four different polymorphic human dinucleotide repeat DNA markers that map on this chromosome arm. The correlations with prognosis were established by the Kaplan-Meier method, and the Cox proportional hazards model was used to identify which independent factors jointly had a significant influence on patient survival.


RESULTS
Overall, allelic losses were detected in 19.5% of the patients evaluated. Only considering informative tumors, the data indicated that LOH was observed in 17 of 71 (29.4%) informative cases. Results from survival analysis showed a significant correlation between this molecular abnormality and both overall survival and disease free survival (P = 0.02 and P = 0.0005, respectively). The worst prognosis was found for the group of patients with LOH at 3p23: This alteration was an independent prognostic factor according to Cox multivariate analysis.


CONCLUSIONS
This study is the first to demonstrate the prognostic significance of LOH at chromosome arm 3p for patients CRC and may help to identify patients who need an intensive postoperative follow-up protocol.
Iniesta
P
P
Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
Massa
M J
MJ
González-Quevedo
R
R
de Juan
C
C
Morán
A
A
Sánchez-Pernaute
A
A
Cerdán
J
J
Torres
A
A
Balibrea
J L
JL
Benito
M
M
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000368:Aged; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D016019:Survival Analysis
D004273:DNA, Neoplasm