ONCOLOGY REPORTS 5: 735-739, 1998 NM23 gene product expression does not predict lymph node metastases or survival in young patients with colorectal cancer STEVEN D.HEYS 1 ' 3 , NEIL LANGLOIS 2 , IAN C. SMITH 1 , LESLIE G. WALKER 1 and OLEG EREMIN 1 Departments of Surgery, Pathology, and Surgical Nutrition and Metabolism Unit, University of Aberdeen, Aberdeen, Scotland, UK Received December 30, 1997; Accepted February 3, 1998 Abstract. NM23 gene product is a putative metastases suppressor gene which has structural homology to a nucleo- side diphosphate kinase. Previous studies examining the relationship between NM23 gene product expression and survival in patients with colorectal cancer have revealed conflicting results. However, no study has focused on young patients with colorectal cancer. This study was carried out to determine if expression of the NM23 gene product was correlated with metastatic potential and survival in young patients (45 years and under) with colorectal cancer. Eighty- one patients with colorectal cancer were studied and the presence of the NM23 gene product (HI) was detected using standard immunohistochemical techniques. NM23 gene product expression did not correlate with tumour stage, lymph node involvement by tumour, presence of distant metastases, extramural vascular invasion or degree of tumour differentiation. Independent risk factors for overall survival were: Dukes' stage (p=0.00001) and extramural vascular invasion (p=0.003). NM23 expression was not an independent prognostic indicator (p=0.55). Therefore, NM23 expression does not correlate with existing indicators of tumour aggressiveness and behaviour nor is it an independent predictor of survival in young patients with colorectal cancer. Introduction Colorectal cancer causes up to 15% of all deaths from cancer in the Western world (1). In the USA there are 147,000 new cases per annum and in Scotland approximately 2,400 per year (2,3). Up to 3% of all cases of colorectal cancer have been reported to occur in young patients, 45 years of age and under (4). The prognosis for this young group of patients when compared with older patients with colorectal cancer is Correspondence to: Mr S.D. Heys, Department of Surgery, Surgical Nutrition and Metabolism Unit, University Medical Buildings, Aberdeen Royal Infirmary, Aberdeen AB9 2ZD, Scotland, UK Key words: colorectal cancer, NM23, young patients unclear. Some studies have reported that young patients have more aggressive tumours and present at a more advanced stage (up to 87% of patients having lymph node and distant metastases at presentation) (5-9). However, others have not documented such differences (see ref. 4 for review). The overall 5-year survival for young patients with colorectal cancer has ranged from 8% to 69%, even when patients have undergone apparently 'curative' surgery (4,8,10). Attempts have therefore been made to try to identify which patients are most at risk of disease recurrence and may benefit most from the administration of adjuvant chemotherapy. Recent interest has focused on the NM23 gene product, a putative metastasis suppressor gene. Three human nm23 genes, Hl, H2 and DR have been identified, located on chromosome 17q22, encoding proteins that are 90% identical (11-14). Experimental studies in cell lines and in animal tumour models have demonstrated that the NM23 protein does prevent tumours from metastasising and may also play a role in the control of growth and development (15). Studies in man have also shown that decreased expression of the NM23 protein and the nm23 gene is associated with a reduced survival in a range of tumours, for example liver, breast, ovary and melanoma (16-19). In colorectal cancers conflicting results have been obtained with reduced expression of NM23 either correlating with a poorer survival (20-22) or having no relationship to metastatic disease (23,24). However, the relationship of NM23 gene product expression to disease spread and survival in young patients with colorectal cancer, to the best of our knowledge, has not yet been investigated. The present study evaluated the relationship of NM23 gene product expression to lymph node metastases, distant disease spread and survival in our cohort of young patients with colorectal cancer. The material used for this study was obtained from a previously reported data base of patients aged 45 years and under with cancer of the colon and rectum (25). Patients and methods Patients. Ninety-two patients with colorectal carcinoma aged 45 years and under presented to the Grampian Hospitals between 1970 and 1990. Details of clinical presentation, disease recurrence (local and distant) and survival were