P53, RETINOBLASTOMA, AND HUMAN PAPILLOMAVIRUS IN SQUAMOUS-CELL CARCINOMA AND ADJACENT NORMAL MUCOSA OF THE UPPER AERODIGESTIVE TRACT

Objective: The primary objective of this study was to determine the in cidence of p53 and retinoblastoma tumor suppressor gene mutations and human papillomavirus infection in squamous cell carcinoma and adjacent normal mucosa of the upper aerodigestive tract. The secondary objecti ve was to associate these findings with clinical and histopathologic f eatures. Design: Point mutations of p53 were identified by single-stra nd conformation polymorphism analysis and confirmed by direct DNA sequ ence analysis. Polymerase chain reaction-based methods were used to id entify loss of heterozygosity of the retinoblastoma tumor suppressor g ene and the presence of human papillomavirus sequences. Settings: Univ ersity-based tertiary care center. Patients or Other Participants: For ty-five consecutive cases of upper aerodigestive tract squamous cell c arcinoma. Results: Eleven point mutations of p53 were identified in tu mor samples (24%). No functional p53 mutations were detected in adjace nt normal tissue from eight of these individuals nor was there evidenc e of p53 alteration in normal tissue adjacent to 12 of 30 additional t umors tested that demonstrated conformational alterations by single-st rand conformation polymorphism analysis. The p53 mutations were signif icantly associated with local invasion. Loss of heterozygosity (which has a 20% chance of random occurrence in tumors) was detected at the r etinoblastoma locus in 15% of the tumors tested. Five of the specimens (11%) were positive for human papillomavirus sequences (two of which also contained p53 mutations). Conclusions: These findings suggest tha t p53 but not retinoblastoma or human papillomavirus is an important p rognostic factor and is involved as a late event in the pathogenesis o f upper aerodigestive tract squamous cell carcinoma.