Full-coverage TP53 deep sequencing of recurrent head and neck squamous cell carcinoma facilitates prognostic assessment after recurrence.

OBJECTIVES: This study aims to evaluate whether the accumulation of TP53 mutations is associated with clinical outcome by comparing full-coverage TP53 deep sequencing of the initial and recurrent head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Medical records and surgical specimens of 400 patients with HNSCC surgically treated with curative intent, of which 95 patients developed local or locoregional recurrence, were reviewed. Of these patients, 63 were eligible for genomic analysis. Full-coverage TP53 deep sequencing of 126 paired initial and recurrent tumor samples was examined using next-generation sequencing (NGS). Temporal changes in the mutation status, molecular characterization, and clinical outcome were compared. Fisher's exact test, Kaplan-Meier method, log-rank test, and Cox regression models were used for statistical analysis. RESULTS: Of the recurrent tumors, 22% harbored accumulation of TP53 mutations, and 16% lost the original mutation. The accumulation of TP53 mutations was significantly more frequent in oral cancer than in pharyngeal or laryngeal cancer (33% vs. 7%, p = 0.016). Two-year post-recurrence survival (PRS) was associated with TP53 status for recurrent tumors, but not for initial tumors. The TP53 status for recurrent tumors was an independent risk factor in multivariate analysis (hazard ratio, 5.76; 95% confidence interval, 1.86-17.8; p = 0.0023). CONCLUSION: Approximately one-third of the recurrent HNSCC cases showed a different TP53 status from the initial tumor. Temporal changes in the mutation status differed by primary site. Full-coverage TP53 deep sequencing of recurrent tumors was useful in predicting post-recurrence prognosis.

Combined assessment of epidermal [corrected] growth factor receptor dual color in situ hybridization and immunohistochemistry with downstream gene mutations in prediction of response to the anti-EGFR therapy for patients with metastatic colorectal cancer.

BACKGROUND AND AIMS: Biomarkers associated with anti-EGFR antibodies therapy have been investigated in metastatic colorectal cancer (CRC). We conducted this study to evaluate the clinical utility of a combined assessment of EGFR status and genomic mutations of the EGFR downstream signal pathway in predicting the efficacy of anti-EGFR antibody treatment. METHODS: We collected formalin-fixed paraffin-embedded tumor tissues and evaluated the EGFR status by immunohistochemistry (IHC), dual color in situ hybridization (DISH) and genomic analyses of KRAS, BRAF, PIK3CA and NRAS by direct sequencing. RESULTS: A total of 129 patients were evaluated in our study. Among KRAS wild-type patients, EGFR DISH positivity was associated with a higher response rate than DISH negativity (56.3 vs. 21.1%, p = 0.011). A subgroup with EGFR DISH positivity plus IHC3+ and wild-type of EGFR downstream gene mutations achieved higher response rate and disease control rate. EGFR DISH positivity, KRAS codon 146 mutation and NRAS codon 61 mutation were prognostic factors in both progression-free survival and overall survival by multivariate analyses. CONCLUSIONS: Combined assessment of DISH plus IHC and EGFR downstream gene mutations was useful to predict the response to anti-EGFR antibodies treatment in metastatic colorectal cancer patients in our study.