OVEREXPRESSION OF NUCLEOSIDE DIPHOSPHATE KINASE A NM23-H1 PROTEIN IN HUMAN LUNG-TUMORS - ASSOCIATION WITH TUMOR PROGRESSION IN SQUAMOUS CARCINOMA/

Levels of nm23-H1/nucleoside diphosphate/kinase A expression have been reported to correlate inversely with metastatic potential in some tum ors but not in others. To clarify the role of nm23 in lung carcinoma, the genetic abnormalities of nucleoside diphosphate/kinase A/nm23-H1 w ere investigated at the DNA and protein levels. A series of 104 human lung tumors (42 neuroendocrine (NE) and 62 non-NE tumors) was analyzed for nm23-H1 protein expression by immunohistochemistry using one poly clonal and two monoclonal Ab and for genomic alterations using Souther n blotting and single-strand conformation polymorphism. Overexpression of the nm23-H1 protein relative to the normal lung epithelia (pneumoc yte and bronchial epithelial cells) was observed in 83% (35/42) of NE carcinomas and in 89% (55/62) of non-NE carcinomas. Eight of nine carc inoids exhibited an increased expression of nm23-H1 protein, suggestin g that this overexpression of the nm23 protein is necessary for prolif eration in any tumors. No significant correlation was found between nm 23 staining and any clinicopathologic parameters in NE carcinoma or in adenocarcinoma. In squamous carcinoma, high levels of nm23-H1 protein expression were associated with tumor stage (p = 0.0036). Allelic del etion or genetic amplification was never found. No altered mobility wa s detected using single-strand conformation polymorphism analysis. The se data show that nm23-H1 protein is overexpressed in a large number o f lung tumors of all histologic types, in association with advanced tu mor stage in squamous carcinoma. They also suggest that nm23-H1 might play a role in the progression of lung tumors rather than in antimetas tatic function.