Metastatic recurrence of early-stage colorectal cancer is linked to loss of heterozygosity on chromosomes 4 and 14q.
OBJECTIVE
To investigate the prognostic value for loss of heterozygosity (LOH) of chromosomes 4 and 14q in early-stage colorectal cancer (CRC).


METHODS
A total of 70, largely microsatellite stable, tumours and their corresponding normal mucosa were subjected to microdissection and analysed for LOH at chromosomes 4 and 14q by using 13 highly polymorphic microsatellite markers. LOH was correlated with the survival of the patients, using univariate, multivariate and Kaplan-Meier's survival curves.


RESULTS
LOH at D4S2935, D4S1579 and D4S1595 on chromosome 4 was significantly associated with metastatic recurrence of early-stage CRC. For chromosome arm 14q, two minimal regions of deletion were associated with metastatic recurrence and mapped to neighbouring markers D14S275/D14S49 at 14q12-13 and D14S65/D14S250 at 14q32. High-level loss (loss of five to eight of the informative microsatellite markers) on both chromosomes 4 and 14q, to be an independent prognostic indicator in early-stage CRC was shown by multivariate analysis.


CONCLUSIONS
Determining the LOH of chromosomes 4 and 14q and their extent in primary tumours of patients with early-stage CRC may constitute a molecular signature of metastatic recurrence. This may be achieved if new finding sheds light on the treatment of this subgroup of patients that have been largely ignored.
Al-Mulla
F
F
Department of Pathology, Faculty of Medicine, Molecular Pathology Unit, Kuwait University, Kuwait. fahd@al-mulla.org
AlFadhli
S
S
Al-Hakim
A H
AH
Going
J J
JJ
Bitar
M S
MS
D000368:Aged; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D004273:DNA, Neoplasm / Q000235:genetics; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D042282:Microdissection / Q000379:methods; D018895:Microsatellite Repeats; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis
D004273:DNA, Neoplasm