Metastasis is the manifestation most directly affecting survival for patients with colorectal carcinoma. Identification of high-risk markers for metastases would allow focused selection of patients for adjuvant chemotherapy. Reports of the relationship between the putative metastasis suppressor NM23 and metastasis and/or survival in colorectal cancer patients are conflicting. The purpose of this study was to separately assess expression of NM23-H1 and NM23-H2 in primary colon cancers and determine whether expression was associated with regional nodal disease and/or liver metastases. Four patient cohorts were selected on the basis of histopathological staging at primary surgery (lymph node status/liver metastasis): -/- (n = 46), +/- (n = 47), -/+ (n = 43), and +/+ (n = 46). Primary tumors were evaluated by semiquantitative immunohistochemical analysis of NM23-H1 and NM23-H2. NM23-H2 expression was not related to survival; however, there was a modest survival advantage with low expression of NM23-H1 (P = 0.027). NM23-H1 expression in the +/+ group was increased compared with the other groups (P < 0.001). The -/+ group had the lowest expression of NM23-H2 (P < 0.001). This analysis distinguishes two high-risk groups of colorectal cancer patients. Prior discrepancies regarding the usefulness of NM23 staining may be explained by the need to evaluate both serotypes in addition to standard histopathological analysis to identify specific “at-risk” groups.
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