Decreased expression of the KAI1 gene involved in progression and metastasis of tongue squamous cell carcinoma

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KAI1 was originally identified in prostate cancer as a metastasis suppressor gene, and frequent down-regulation of KAI1 expression was reported in many tumor types. The aim of the present study was to examine whether suppressed expression of KAI1 could contribute to the progression and metastasis of tongue squamous cell carcinoma (SCC). We analyzed mutational status of the KAI1 gene, and both the mRNA and protein level in a series of tongue SCC (25 pre-cancerous lesions, 41 primary tongue SCCs, and 15 metastatic lymph node tumors). We found no mutation of the KAI1 gene by PCR-SSCP analysis, however, immunohistochemistry revealed high frequencies of KAI1 down-regulation not only in metastatic tumors (100%, 15/15) but also in primary tongue SCCs (85%, 35/41) and pre-cancerous lesions (44%, 11/25). There was a significant relationship between down-regulation of KAI1 protein expression and primary tumors with lymph node metastases (P=0.044). Moreover, differentially suppressed expression levels of KAI1 were detected through multiple steps of tumor progression (from normal tissue to carcinoma or metastatic tumor) (P<0.01). Our data suggest that suppressed regulation of KAI1 protein expression is associated with regional lymph node metastasis and that the down-regulation of KAI1 is involved in the tumor progression.
2008-12-01