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

• Published in: Journal of molecular medicine (Berlin, Germany) Vol. 78; no. 2; pp. 111 - 118
• Main Authors: PAVELIC, K, KAPITANOVIC, S, RADOSEVIC, S, BURA, M, SEIWERTH, S, PAVELIC, L. J, UNUSIC, J, SPAVENTI, R
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01-01-2000
• Subjects: Adult; Aged; Biological and medical sciences; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - mortality; Dysplasia; Female; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - mortality; Humans; Immunohistochemistry; Male; Medical sciences; Middle Aged; Monomeric GTP-Binding Proteins - genetics; Monomeric GTP-Binding Proteins - metabolism; NM23 Nucleoside Diphosphate Kinases; Nucleoside-Diphosphate Kinase; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Prognosis; RNA, Messenger - metabolism; Survival Rate; Transcription Factors - genetics; Transcription Factors - metabolism; Tumors; Human; Immunohistochemistry; Pathology; Squamous cell carcinoma; Prognosis; Head and neck; ENT disease; Malignant tumor; Molecular biology; Gene expression
• ISSN: 0946-2716; 1432-1440
• 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.