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Background and Objectives:Expression of HMGI(Y), a nucleoprotein that binds to A/T rich sequences in the minor groove of the DNA helix, is observed in neoplastically transformed cells but not in normal cells. We have analyzed HMGI (Y) expression in the head and neck squamous cell carcinoma and evaluated its clinicopathologic significance. Materials and Methods:HMGI(Y) mRNA was measured by RT-PCR and immunohistochemical staining for HMGI(Y) was performed in the head and neck squamous cell carcinoma. Results:Expression of HMGI(Y) by immunohistochemical staining was observed in 35 of 40 (87.5%) head and neck squamous cell carcinoma samples, whereas normal mucosa and/or the mucosa adjacent to the tumor tissue showed negative or weakly positive staining (p<0.05). Semiquantification of HMGI(Y) by RT-PCR were 2.98±2.24 in cancer and 0.47±0.25 in normal tissue (p<0.001). High expression of HMGI(Y) was observed in well differentiated group and recurrent cases compared to the less differentiated group and/or non-recurrent cases (p<0.05). But no significant correlation was observed between the levels of HMGI(Y) expression and other clinical factors such as stage, tumor size and cervical lymph node metastasis. Conclusion:We think that the HMGI(Y) gene plays some roles in carcinogenesis and cellular proliferation of the head and neck squamous cell carcinoma. HMGI(Y) gene can be used as a cancer marker, but the correlation between the gene expression and the prognosis of the cancer patient should be proved in the future studies. (Korean J Otolaryngol 2002;45:594-600)