Diffuse mode of tumor cell invasion and expression of mutant p53 protein but not of p21 protein are correlated with treatment failure in oral carcinomas and their metastatic foci.

Lack of control of metastatic foci is the most prevalent cause of death in patients with oral carcinomas, and it is important for tumor control to identify the factors that predispose patients to death. In the present study, we examined 225 patients with oral squamous cell carcinoma and investigated the immunohistopathological characteristics of 43 tumors that led to death, comparing them with those of the non-lethal tumors. In the 43 patients, lack of control of the primary site, lymph node and distant metastatic tumors were noted in 20, 18 and 16 patients, respectively. The mode of tumor cell invasion was closely correlated with death. The diffuse invasion modes of grades 4C and 4D were observed in 15 (34.9%) of the 43 tumors with a poor outcome and in 35 (19.2%) of the 182 controlled tumors (p < 0.02). The expression of p53 was highly correlated with death. Of the tumors with poor prognosis, p53 protein was expressed in 32 tumors (76.2%). However, p53 protein expression was observed in 52.7% of the tumors with good prognosis (p < 0.02). In contrast, the expression of p21 protein in the well-controlled tumors (30.4%) was almost equal to that of the 43 lethal tumors (26.2%). Compared with the ratios of local recurrence, metastases and their treatment failures in the p53-negative grade 1 and 2 tumors, those in the mutant p53-positive grade 3, 4C and 4D tumors were mostly high. These results indicate that measuring p53 protein expression and evaluating the mode of tumor cell invasion are important for oral carcinoma therapy because the expression of mutant p53 protein and the diffuse modes of tumor cell invasion indicate a predisposition toward a poor prognosis. Copyright 2000 S. Karger AG, Basel