Increased activity of nm23-H1 gene in squamous cell carcinoma of the head and neck is associated with advanced disease and poor prognosis

The present study was undertaken to determine whether the nm23-H1 gene is e xpressed in squamous cell carcinoma of the head and neck (SCCHN) and whethe r the level of nm23-H1 protein or mRNA in cells vary as they progress to a more malignant phenotype. Of the 120 SCCHN studied 54 (45%) stained positiv ely for nm23-H1 protein. Protein expression was significantly higher in mor e advanced stages of disease. Expression of nm23-H1 was significantly highe r in cancer tissues than in normal, adjacent tissue, dysplasia, or carcinom a in situ, The nm23-H1 rate increased with progression of synchronous lesio ns from dysplasia to carcinoma in situ and finally to carcinoma (P<0.05). N orthern blot analyses of tissues with various clinicopathological character istics also revealed differences in nm23-H1 mRNA expression. When levels of nm23-H1 mRNA were compared to tumor stage, intensity of expression was fou nd to be higher in stages 3 and 4 than stages 1 and 2 (P<0.01), Malignant t umors had a higher level of mRNA nm23-H1 expression than normal or premalig nant tissues. The nm23-H1 negative patients survived significantly longer t han nm23-H1 positive ones (P<0.05). To study the possible relationship betw een nm23-H1 gene expression and cell growth rate in tumor cells, the mRNA l evel in each tumor was compared to proliferative activity. The nm23-H1 gene expression levels were directly related to the [H-3]thymidine labeling ind ex in tumor cells (R=0.6681). Our results strongly indicate that the nm23-H 1 gene is involved in progression of SCCHN. Together with results obtained on lung cancer, our observations suggest that increased expression of nm23- H1 in cancers of the upper aerodigestive tract may have different implicati ons than elsewhere in the body.