Abstract
Background
This study elucidates the clinical impact of surgical treatment of head and neck squamous cell carcinoma (HNSCC) based on a detailed search of all exons of the TP53 gene and p53 protein phenotypic analysis using formalin-fixed paraffin-embedded (FFPE) specimens.
Methods
Clinically well-annotated FFPE specimens from 317 patients with HNSCC treated by surgery were examined by all-exon TP53 sequencing using a next-generation sequencer and p53 protein phenotype by immunohistochemistry. After excluding human papillomavirus-associated oropharyngeal carcinomas, two risk categories were classified as “p53 adverse function” and “p53 favorable function” based on TP53 mutation status and p53 protein phenotype. Mutation in PIK3CA, AKT, and HRAS was also evaluated by target sequence. Cox proportional hazards regression models were used for statistical analysis of clinical outcomes. Receiver operating characteristic curve analysis was used to determine the optimal surgical margin cutoff for local recurrence. Local control rates were compared between the risk groups using Fisher’s exact test.
Results
Multivariate analysis identified “p53 adverse function” as an independent poor predictor of overall survival, local control, and distant metastasis-free survival. In oral cavity cancer, the optimal surgical margin cutoff associated with local recurrence was 6 mm. In patients with surgical margin > 6 mm, the “p53 adverse function” group demonstrated significantly higher local recurrence rate than the “p53 favorable function” group. PIK3CA, AKT, or HRAS mutation did not correlate with improved overall survival.
Conclusions
All-exon TP53 sequencing and p53 protein phenotype analysis using FFPE specimens can accurately predict clinical outcomes.
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Acknowledgements
We acknowledge Yuki Saito, MD, PhD for his substantial contribution to critical manuscript revisions. The authors wish to thank Mr. Kensuke Suzuki (Illumina Inc.) for technical support. We also thank Ms. Sachiko Miura, Ms. Toshiko Sakaguchi, and Ms. Chizu Kina for skillful technical assistance.
Funding
This work was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant nos. 16K20232 to K.K. and 17K08710 to T.M.
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Kobayashi, K., Yoshimoto, S., Matsumoto, F. et al. All-Exon TP53 Sequencing and Protein Phenotype Analysis Accurately Predict Clinical Outcome after Surgical Treatment of Head and Neck Squamous Cell Carcinoma. Ann Surg Oncol 26, 2294–2303 (2019). https://doi.org/10.1245/s10434-019-07287-x
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DOI: https://doi.org/10.1245/s10434-019-07287-x