Expression of IAP and p53 in oral carcinogenesis

Objectives: To investigate the expression of inhibitors of apoptosis family (IAP family) in human oral premalignant & malignant epithelial lesions and its implication with p53 accumulation and epigenetic mechanism. Methods: From January 1991 to December 2001, 44 out of 1458 patients diagnosed with various oral pre-malignant lesions in the Department of Oral Pathology, Kaohsiung Medical University Hospital were found to develop malignant epithelial lesions. Immunohistochemical staining was performed to investigate the expression of five IAP members (survivin, XIAP, cIAP1, cIAP2 & NAIP) & their relationship with p53 status in both premalignant & transformed malignant lesions. Semi-quantitative RT-PCR & PCR-based methylation assay were also performed. Five normal oral mucosa & 10 oral malignant lesions were used as negative & positive controls respectively. Results: Neither survivin nor cIAP2 (protein and mRNA) could be detected in any of the normal tissues whereas both mRNA & protein of survivin & cIAP2 were significantly increased in malignant tissues. However, both mRNA & protein expression of XIAP, cIAP1 & NAIP for malignant lesions were elevated significantly as compared with the normal tissues. Moreover, mRNA expression of these five IAP members was significantly correlated to each other. p53 (both protein and mRNA) was not detected in any normal tissues. Expression of these five IAPs & p53 proteins were significantly increased in malignant tissues compared with premalignant tissues. The PCR-based methylation assay showed that the expression of IAPs was controlled by an epigenetic mechanism. Conclusion: Our results suggest that IAP family could play an important role oral squamous-cell carcinogenesis and that their expression may be modulated by both genetic (mutant p53) and epigenetic mechanism.