Chihiro Sugiura

Specific p53 mutations predict poor prognosis in oral squamous cell carcinoma

In this study, we focused on p53 mutations in specific regions, including DNA-binding surface regions, to clarify the correlation between mutations within the specific regions of p53 and clinical outcomes of patients with oral cancers. We analyzed p53 mutations in 121 fresh primary oral squamous cell carcinomas (SCCs) by polymerase chain reaction-single-strand conformation polymorphism or a yeast functional assay. p53 mutations were detected in 51/121 (42%) cases. Mutation of p53 was not associated with any clinicopathological parameters; however, tumors containing specific p53 mutations, e.g. DNA-binding surface regions (L2, L3 and the LSH motif) and conserved regions (II-V), had significantly poorer prognoses than tumors with mutations outside of those regions. Moreover, locoregional failure, lymph node metastasis and the occurrence of subsequent distant metastasis were also significantly associated with mutations within DNA-binding surface regions. These data indicate that specific mutations of p53 could be important prognostic factors in oral SCCs.

Characteristics of mutations in the p53 gene of oral squamous-cell carcinomas associated with betel-quid chewing in Sri Lanka

Oral squamous‐cell carcinoma (SCC) is the most common neoplasm in Sri Lanka, accounting for approximately 30% of all cancers in males. Epidemiologic evidence indicates that there is an unequivocal relationship between betel chewing and oral carcinogenesis, suggesting that there may be specific genetic targets of betel‐quid ingredients. The p53 gene has been indicated to be a tumor‐suppressor gene that is found in mutated form in common human cancers; however, there are few reports about “carcinogen‐specific” p53 mutation. Because of this background, primary resected specimens from 23 oral SCCs, 7 leukoplakias and 2 oral submucous fibrosis were collected from oral SCC patients in Sri Lanka and were used for p53 mutation analysis. Exons 5 through 8 of the p53 gene were examined by polymerase chain reaction‐single‐strand conformation polymorphism (PCR‐SSCP) and direct sequencing. Mutations in the p53 gene were frequent (10/23) in oral SCC specimens from Sri Lanka. Moreover, the mutations clustered significantly in exon 5 (7/10) of the p53 gene, and small deletions and inclusions other than point mutations were observed. These results indicate that 1) betel‐quid chewing may cause specific genetic changes, including mutation in the p53 gene; 2) mutations in the p53 gene are not rare events in SCC patients who are betel‐quid chewers, which contrasts with other reports; 3) exon 5 of the p53 gene could be one of the specific targets for some betel‐quid ingredients; and 4) betel‐quid chewing may be a critical environmental factor in the development of oral SCC. Int. J. Cancer 77:839–842, 1998.© 1998 Wiley‐Liss, Inc.

Expression pattern of p63 in oral epithelial lesions and submucous fibrosis associated with betel-quid chewing in Sri Lanka

Betel-quid chewing, which is closely related to the high incidence of oral cancer, is prevalent in Sri Lanka. p63 has a remarkable structural similarity to p53, suggesting an aberrant expression in oral cancer. Using anti-p63 antibody and immunohistochemistry, the present study investigated the expression pattern of p63 in oral epithelial lesions, including different types of squamous cell carcinoma (SCC), different grades of epithelial dysplasia, and submucosal fibrosis associated with betel-quid chewing. Nuclear immunoreactivity for p63 was detected in all the cases, including normal oral epithelium and epithelial lesions. In normal oral epithelium, nuclear positivity for p63 was observed in some of the basal cell layers and focally in the parabasal layer. Nuclear positivity increased in the epithelial lesions. The percentage of positive nuclei in the epithelial lesions was significantly higher than in normal epithelium (P < 0.01) and was also significantly higher in oral submucosal fibrosis than in epithelial dysplasia (P < 0.05). The results indicate that the overexpression of p63 in oral precancerous lesions and SCC in betel-quid chewers in Sri Lanka may be a useful marker for oral precancerous lesions.

XENOGENIZATION OF TUMOR CELLS BY TRANSFECTION WITH PLASMID CONTAINING env GENE OF FRIEND LEUKEMIA VIRUS

A rat hepatocellular carcinoma cell line (cKDH‐8 cl‐11) showed decreased tumorigenicity after transfection with an envelope gene derived from a Friend leukemia virus (FV‐env gene). FV‐env gene product was found by indirect immunofluorescence staining to be expressed on the cell surface of the FV‐env gene‐transfected cells. The FV‐env‐transfected cells (FV‐env cKDH‐8), however, grew well in X‐irradiated immunosuppressed rats, indicating that the reduction in tumorigenicity of the transfected cells is based on immunological reaction in the host. The rats which rejected FV‐env cKDH‐8 cells showed resistance to rechallenge with the parent cKDH‐8 cl‐11 tumor cells. These results suggest that the FV‐env gene product may elicit antitumor immunity against FV‐env cKDH‐8 cells in a host with a resultant reduction in the tumorigenicity of these cells.