ORIGINAL ARTICLE

Ki-ras gene mutations, LOH of the APC and DCC genes, and microsatellite instability in primary colorectal carcinoma are not associated with micrometastases in pericolonic lymph nodes or with patients’ survival

N P Zauber¹, C Wang², P S Lee³, T C Redondo⁴, D T Bishop⁶, A Goel⁵

¹ Department of Medicine, Saint Barnabas Medical Center, Livingston, NJ 07039, USA
² Department of Pathology, Saint Barnabas Medical Center
³ Department of Pathology, Saint Barnabas Medical Center
⁴ Department of Pathology, Saint Barnabas Medical Center
⁵ Department of Medicine, Saint Barnabas Medical Center
⁶ Genetic Epidemiology Division, Cancer Research UK Clinical Centre in Leeds, St James’s University Hospital, Leeds LS9 7TF, UK

Correspondence to:
Correspondence to:
Dr N P Zauber
Department of Medicine, Saint Barnabas Medical Center, Livingston, NJ 07039, USA; pzauber{at}aol.com

Aims: The primary aim of this study was to look for possible correlations between molecular genetic changes in primary colorectal cancer and the presence or absence of micrometastases in the accompanying pericolonic lymph nodes. The secondary aim was to correlate the data on these molecular genetic changes and micrometastases with survival.

Methods: One hundred and twenty five Dukes’s stage B colorectal cancers from 1989 to 1992 were analysed. The primary tumours were evaluated for Ki-ras mutation, adenomatous polyposis coli (APC) loss of heterozygosity (LOH), deleted in colon cancer (DCC) LOH, and microsatellite instability using standard molecular techniques. All available lymph nodes were immunohistochemically stained for micrometastases.

Results: Micrometastases were present in 41% of patients. There were significantly more lymph nodes removed in the patients with micrometastases. Micrometastases were not associated with Ki-ras mutation, APC LOH, DCC LOH, or microsatellite instability, even when controlling for the number of lymph nodes removed. None of the molecular variables considered had a significant impact on either overall survival or on death with disease.

Conclusions: There are insufficient data to justify using molecular genetic changes in primary colorectal carcinomas as prognostic markers. Micrometastases do not provide prognostic information on survival. There is value in increasing the numbers of lymph nodes removed and analysed along with the primary tumour.

Abbreviations: APC, adenomatous polyposis coli; DCC, deleted in colon cancer; H&E, haematoxylin and eosin; LOH, loss of heterozygosity; MSI, microsatellite instability; PCR, polymerase chain reaction; SSCP, single stranded conformation polymorphism

Keywords: APC gene; Dukes’s B colon cancer; Ki-ras gene; micrometastases

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