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

J Mol Med (Berl). 2000;78(2):111-8. doi: 10.1007/s001090000081.


The present study was undertaken to determine whether the nm23-H1 gene is expressed in squamous cell carcinoma of the head and neck (SCCHN) and whether 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 positively for nm23-H1 protein. Protein expression was significantly higher in more advanced stages of disease. Expression of nm23-H1 was significantly higher in cancer tissues than in normal, adjacent tissue, dysplasia, or carcinoma in situ. The nm23-H1 rate increased with progression of synchronous lesions from dysplasia to carcinoma in situ and finally to carcinoma (P<0.05). Northern blot analyses of tissues with various clinicopathological characteristics also revealed differences in nm23-H1 mRNA expression. When levels of nm23-H1 mRNA were compared to tumor stage, intensity of expression was found to be higher in stages 3 and 4 than stages 1 and 2 (P<0.01). Malignant tumors had a higher level of mRNA nm23-H1 expression than normal or premalignant tissues. The nm23-H1 negative patients survived significantly longer than nm23-H1 positive ones (P<0.05). To study the possible relationship between nm23-H1 gene expression and cell growth rate in tumor cells, the mRNA level in each tumor was compared to proliferative activity. The nm23-H1 gene expression levels were directly related to the [3H]thymidine labeling index in tumor cells (R=0.6681). Our results strongly indicate that the nm23-H1 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 implications than elsewhere in the body.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality
  • Female
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / mortality
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Monomeric GTP-Binding Proteins / genetics*
  • Monomeric GTP-Binding Proteins / metabolism*
  • NM23 Nucleoside Diphosphate Kinases
  • Nucleoside-Diphosphate Kinase*
  • Prognosis
  • RNA, Messenger / metabolism
  • Survival Rate
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*


  • Biomarkers, Tumor
  • NM23 Nucleoside Diphosphate Kinases
  • RNA, Messenger
  • Transcription Factors
  • NME1 protein, human
  • Nucleoside-Diphosphate Kinase
  • Monomeric GTP-Binding Proteins