Expression of nm23-H1 predicts lymph node involvement in colorectal carcinoma

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Abstract
Reduced expression of the metastasis suppressor gene nm23-H1 has previously been correlated with high tumor metastatic potential and fatal clinical outcome in some tumors (e.g., breast). For colorectal carcinomas, the findings are equivocal. We have used a monoclonal antibody against nm23-H1 to investigate the expression in colorectal carcinomas at the time of primary curative surgery (RO resection) to assess if there was any relation between nm23-H1 expression and stage or histologic grade at the time of primary tumor removal. Of 100 colorectal carcinomas studied (Stages I, II, and III according UICC, all resected curatively), nm23-H1 immunoreactivity was weak in 41 (41 percent), moderate in 24 (24 percent), and strong in 35 (35 percent) cases. The grade of positivity against nm23-H1 was significantly lower in advanced stages of the disease (Stages II or III) (P <0.001, chi-squared=52.8). In tumors with low or weak immunoreactivity against nm23-H1, frequency of lymph node metastases was significantly higher compared with those with moderate or strong staining (P <0.001; chi-squared=50.58). Therefore, with a sensitivity of 93 percent and a specificity of 58 percent, low nm23-H1 immunoreactivity of the primary tumor, assessed at the time of surgery, is an indicator of the presence of lymph node metastases. Immunohisto-chemical evaluation of nm23-H1 in the primary tumor or in a biopsy is a useful predictor of stage of disease and presence of lymph node metastases in colorectal carcinomas and may have clinical significance, e.g., in predicting optimal therapeutic regimes.