Unexpected close surgical margin in resected buccal cancer: Very close margin and DAPK promoter hypermethylation predict poor clinical outcomes

Hon Yi Lin, Tze Ta Huang, Moon Sing Lee, Shih Kai Hung, Ru Inn Lin, Chih En Tseng, Shu Mei Chang, Wen Yen Chiou, Feng Chun Hsu, Wen Lin Hsu, Dai Wei Liu, Yu Chieh Su, Szu Chi Li, Michael W.Y. Chan

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Objectives: In resected buccal cancer patients, an unexpected close surgical margin has been observed to correlate with poor clinical outcomes. However, close surgical margin alone does not independently guide post-operative therapies, revealing a clinical debate. Hence, the present study intended to explore epigenetic-based bio-predictors for further stratifying this debating patient population. Materials and methods: Between 2000 and 2008, we retrospectively recruited 44 resected buccal cancer patients with a close surgical margin of ≤5 mm. All patients had post-operative radiotherapy. Genomic DNA was extracted from tumor-enrich areas that contained cancer cells of >70%. Methylation-specific PCR was performed to detect promoter methylation of four tumor suppressor genes, including RASSF1A, DAPK, IRF8, and SFRP1. Post-irradiation locoregional control was defined as the primary end point. Results: There were 40 males and 4 females, with a median age of 53.5 years (range, 32-82 years). Multivariate analysis identified two independent predictors for locoregional recurrence: very close margin of ≤1 mm (HR: 4.96; 95% CI, 1.63-15.09; P = 0.018) and promoter hypermethylation of DAPK (HR: 2.83; 95% CI, 1.05-7.63; P = 0.042). The highest risk of locoregional recurrence was observed in patients with both of the two factors (HR, 8.05; 95% CI, 2.56-25.82; P = 0.002) when compared with patients with none. Shorter disease-free survival, but not overall survival, was also observed. Conclusion: More aggressive managements should be considered in resected buccal cancer patients with both very close margin and DAPK promoter hypermethylation rather than post-operative observation or radiotherapy alone.

Original languageEnglish
Pages (from-to)336-344
Number of pages9
JournalOral Oncology
Volume49
Issue number4
DOIs
Publication statusPublished - 2013 Apr

All Science Journal Classification (ASJC) codes

  • Oral Surgery
  • Oncology
  • Cancer Research

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