Immunohistochemical detection of p53 protein accumulation in head and neckcancer: Correlation with p53 gene alterations

The genetic and functional status of the p53 gene may be an important facto r in guiding therapeutic strategies for patients with cancer. The purpose o f this study was to determine whether p53 immunohistochemistry (LHC) accura tely reflects the mutational status of the p53 gene and to determine whethe r p53 IHC independently predicts tumor responsiveness to radiation therapy for patients with HNSCC. p53 MC was performed using the monoclonal antibody DO7 on tumors from 85 patients with HNSCC treated with primary or adjuvant radiation. The p53 status in all of these tumors was previously assessed b y direct sequence analysis of exons 5 through 9: 49 tumors were p53 wild-ty pe, and 36 harbored p53 gene mutations. All patients were well characterize d with respect to locoregional recurrence, distant spread, and survival. Po sitive p53 staining was observed in 53 of the 85 cases (62%). Only 27 (51%) of these 53 MC-positive cases harbored gene mutations in exons 5 through 9 ; 23 (72%) of the 32 IHC-negative cases did not harbor mutations. The overa ll correlation rate between MC and sequencing was 59% (P < .04, chi(2)) Dis cordant results were observed for 35 (41%) cases, including 26 MC-positive cases and 9 MC-negative cases. In 7 of 9 cases, false-negative staining was due to a nonsense or splice-site mutation. p53 MC was not predictive of ov erall survival (P = .37) or disease-free survival (P = .95). In a sizable n umber of cases, p53 IHC does not reflect the mutational status of the p53 g ene. Specific types of alterations (eg, truncating mutations) and other fac tors may contribute to this poor correlation. Moreover, p53 MC does not app ear to be an independent predictor of tumor responsiveness to radiation in patients with HNSCC. Copyright (C) 1999 by W.B. Saunders Company.