p53 mutation as a prognostic marker in advanced laryngeal carcinoma

Objective: To determine the relationship of p 53 mutations in advanced laryngeal carcinomas to p53 immunohistochemistry, organ preservation, and patient survival. Design: Paraffin-embedded tumor specimens were obtained from patients enrolled in the Department of Veterans Affairs Laryngeal Cancer Cooperative Study, a multi-institutional randomized clinical trial comparing induction chemotherapy (cisplatin and fluorouracil) plus radiation therapy with surgery plus postoperative radiation therapy. Tumor specimens were analyzed for p 53 mutations in exons 5 through 8 by using single-strand conformational polymorphism (SSCP) analysis followed by DNA sequencing of all variants. Fiveyear follow-up data were available for all patients studied. Subjects: Forty-four patients enrolled in the Department of Veterans Affairs Laryngeal Cancer Cooperative Study from whom paraffin-embedded tumor specimens were readily available. Results: p53 immunostaining did not correlate with p 53 SSCP and DNA sequencing results. More than half (62% [16/26]) of the tumors that overexpressed p53 immunohistochemically did not have a detectable p 53 gene mutation. Similarly, 39% (7/18) of tumors that did not overexpress p53 did have a p 53 gene mutation. p 53 mutations were present in 39% of tumors tested. Mutations within exon 5 made up 41% of p 53 gene mutations in laryngeal carcinomas. Transitions were the most common type of mutation in this study (92% of mutations). Conclusions: The presence of a p 53 mutation as detected by SSCP is associated with decreased patient survival. Further study is required to confirm this relationship and to determine whether specific p 53 mutations predict organ preservation. Arch Otolaryngol Head Neck Surg. 1997;123:605-609