ORIGINAL ARTICLE

Metastatic recurrence of early-stage colorectal cancer is linked to loss of heterozygosity on chromosomes 4 and 14q

F Al-Mulla¹, S AlFadhli², A H Al-Hakim¹, J J Going³, M S Bitar⁴

¹ Department of Pathology, Faculty of Medicine, Molecular Pathology Unit, Kuwait University, Kuwait
² Department of Medical Laboratory Sciences, Faculty of Allied Health, Kuwait University, Kuwait
³ Department of Pathology, University of Glasgow, Glasgow, UK
⁴ Department of Pharmacology, Faculty of Medicine, Kuwait University

Correspondence to:
Correspondence to:
Dr F Al-Mulla
Department of Pathology, Faculty of Medicine, Kuwait University, PO Box 24923, Safat 13110, Kuwait; fahd{at}al-mulla.org

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.

Result: 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.

Conclusion: 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.

Abbreviations: CRC, colorectal cancer; LOH, loss of heterozygosity

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