Pathogenesis of Multiple Squamous Cell Carcinomas in the Oral Cavity: Clinicopathological and immunohistochemical study of 31 patients

Carcinomas of the oral cavity sometimes arise as multiple, independent lesions and this observation has led to the concept of field cancerization. Howerever, the mechanism of multiple occurrences of oral squamous cell carcinoma (OSCC) is still unknown. Thirty-one cases of synchronous and/or metachronous multiple OSCCs were selected from biopsy and operation materials of the Dental Hospital, Tokyo Medical and Dental University. Histopathogenetic study and investigation were carried out. The clonality of the tumor tissues was analyzed by immunohistochemistry for Ki-67, Bcl-2, p53, cyclinB1 and cyclinD1. Histologic observation showed two patterns of occurrence of OSCC: de novo type and premalignancy-associated type. Twenty-one patients with multiple OSCCs were classified into 3 groups. Group I was de novo type, Group II was mixed type and Group III was premalignacy-associated type. Seventeen of 21 patients (80.9%) revealed p53-positivity in the epithelium apart from the tumor. Fifty-two of 69 tumors (75.4%) showed a different expression rate between Cyclin B1 and Cyclin D1. This data suggests that those patients are at high risk of developing second primary tumors. It also suggests the possibility of polyclonal development of the multiple OSCCs.