Risk factors of metastasis in oral squamous cell carcinomas.

Lymph node and distant metastasis were comparatively studied in 225 oral carcinomas, and factors predisposing toward metastasis were investigated using clinical and immunohistopathological approaches. Neither the sites of tumors nor T-stage was correlated with either type of metastasis. Tumor cell differentiation was weakly correlated with lymph node metastasis, and stromal reaction (the degree of cell infiltration) did not differ greatly between metastasis-positive and negative tumors, although natural killer (NK) activities were correlated with lymph node metastasis. However, the mode of tumor cell invasion was closely associated with both lymph node and distant metastases. In grade 4C and 4D tumors, distant and lymph node metastases were observed in 8 (16%) and 31 (62%) cases, respectively, while of 68 grade 1 and 2 tumors, distant metastasis was not observed in any, and lymph node metastasis occurred in only 15 (22. 1%). In addition, the expression of p53 protein was correlated with lymph node metastasis; of 70 tumors without p53 protein expression, 23 (32.9%) revealed lymph node metastasis, while it occurred in 54 out of 96 tumors positive for p53 protein. However, p53 protein expression was not associated with distant metastasis, and p24 protein, a cyclin-dependent kinase inhibitor, did not show any relationship with either type of metastasis. These results indicate that lymph node metastasis is correlated with multiple factors in the host and tumor cells, but distant metastasis is only correlated with the mode of tumor cell invasion, suggesting that the former can be highly accurately predicted by invasion mode, p53 protein expression and NK activity.