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Norris K. Lee, MD; Yun-Wei Ye, MS; Jun Chen, MD; Xiaohua Li, MD; Pamela G. Waber, MLA; Perry D. Nisen, MD, PhD

Arch Otolaryngol Head Neck Surg. 1993;119(10):1125-1131.

Abstract
Objective
The primary objective of this study was to determine the incidence 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 objective was to associate these findings with clinical and histopathologic features.

Design
Point mutations of p53 were identified by singlestrand conformation polymorphism analysis and confirmed by direct DNA sequence analysis. Polymerase chain reaction—based methods were used to identify loss of heterozygosity of the retinoblastoma tumor suppressor gene and the presence of human papillomavirus sequences.

Setting
University-based tertiary care center.

Patients or Other Participants
Forty-five consecutive cases of upper aerodigestive tract squamous cell carcinoma.

Results
Eleven point mutations of p53 were identified in tumor samples (24%). No functional p53 mutations were detected in adjacent normal tissue from eight of these individuals nor was there evidence of p53 alteration in normal tissue adjacent to 12 of 30 additional tumors tested that demonstrated conformational alterations by single-strand conformation polymorphism analysis. The p53 mutations were significantly associated with local invasion. Loss of heterozygosity (which has a 20% chance of random occurrence in tumors) was detected at the retinoblastoma 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 that p53 but not retinoblastoma or human papillomavirus is an important prognostic factor and is involved as a late event in the pathogenesis of upper aerodigestive tract squamous cell carcinoma.

(Arch Otolaryngol Head Neck Surg. 1993;119:1125-1131)

Author Affiliations
From the Departments of Otolaryngology—Head and Neck Surgery (Dr Lee and Ms Ye) and Pediatrics (Drs Chen, Li, and Nisen and Ms Waber), University of Texas Southwestern Medical Center, Dallas.

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