The role of nm23-H1 in the progression of transitional cell bladder cancer.

The nm23 gene was initially cloned as a metastasis suppressor gene, but the clinical relevance of nm23-H1 as a metastasis suppressor or prognostic indicator for human cancers remains enigmatic. Given that gene expression is regulated at the tissue-specific level, we studied the molecular mechanisms of nm23-H1 expression in human bladder cancer cell lines and the clinical importance of protein product (NM23-H1) in association with patient outcome (n = 257) by immunohistochemistry. We demonstrated that nm23-H1 is expressed in bladder cancer cells without genomic alterations. High NM23-H1 expression was found in 39 cases (15.2%), intermediate expression in 119 cases (46.3%), and low NM23-H1 in 99 cases (38.5%). NM23-H1 was inversely related to staging classification or tumor size (P < 0.05), with the most significant difference being observed between pTa tumors and those of pT1-pT3 bladder cancer (P = 0.01). Reduced NM23-H1, defined as intermediate and low levels of expression, tended to have a higher risk of tumor metastasis (P = 0.06) or poor longtime survival (P = 0.07). In the subset of grade 2 bladder tumors, reduced NM23-H1 significantly correlated with the occurrence of tumor metastasis or poor patient survival (P < 0.05). These findings overall suggest that nm23-H1 may play an important role in suppressing the early step of carcinogenesis and thus act as an invasion suppressor for human bladder cancer. A prospective study is required to clarify the potential of the molecular marker in prediction of disease progression.