p53 Mutation as a Prognostic Marker in Advanced Laryngeal Carcinoma

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Abstract
Objective: To determine the relationship ofp53 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 forp53 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 withp53 SSCP and DNA sequencing results. More than half (62% [16/26]) of the tumors that overexpressed p53 immunohistochemically did not have a detectablep53 gene mutation. Similarly, 39% (7/18) of tumors that did not overexpress p53 did have ap53 gene mutation.p53 mutations were present in 39% of tumors tested. Mutations within exon 5 made up 41% ofp53 gene mutations in laryngeal carcinomas. Transitions were the most common type of mutation in this study (92% of mutations). Conclusions: The presence of ap53 mutation as detected by SSCP is associated with decreased patient survival. Further study is required to confirm this relationship and to determine whether specificp53 mutations predict organ preservation. Arch Otolaryngol Head Neck Surg. 1997;123:605-609