1. ¹Department of Head and Neck Surgery, Institut Gustave-Roussy, 39, Rue Camille Desmoulins, Villejuif 94805, France
2. ²Department of Surgical Oncology, National Cancer Center Singapore, 11 Hospital Drive, Singapore 169610, Singapore
3. ³Translational Research Laboratory, Institut Gustave-Roussy, Rue Camille Desmoulins, Villejuif 94805, France
4. ⁴Department of Biostatistics, Institut Gustave-Roussy, Rue Camille Desmoulins, Villejuif 94805, France
5. ⁵Department of Pathology, Institut Gustave-Roussy, Rue Camille Desmoulins, Villejuif 94805, France
6. ⁶Université Pierre et Marie Curie, 4 Place Jussieu, Paris 75005, France

Correspondence: Dr S Temam, E-mail: Temam@igr.fr

Received 9 May 2008; Accepted 27 May 2008; Published online 1 July 2008.

Abstract

This study sought to determine whether the presence of hypermethylated genes in the surgical margins can predict local recurrences in head and neck squamous cell carcinomas (HNSCCs). We prospectively collected tumour and surgical margin specimens from patients with HNSCCs who had undergone surgical resections. Quantitative methylation-specific PCR (QMSP) of CDKN2A, CCNA1 and DCC were performed in these specimens and correlated with clinical data. Of the 42 patients eligible for the study, 27 were hypermethylation informative for the above three genes. This latter group was associated with longer disease-free survivals (P=0.007) and longer time to disease-specific deaths (P=0.004). Multivariate analyses confirmed hypermethylation non-informative tumours as an independent prognosticating factor for disease-specific deaths (risk ratio 3.8, P=0.026). Quantitative MSP of the margins of 24 hypermethylation informative tumours revealed that 11 patients had molecularly positive margins, of which, five developed disease-specific events (DSEs, three local recurrences and two metastases), compared to none in patients with molecularly negative margins, after a median follow-up of 48 months. Log-rank analyses showed that molecularly positive margins were associated with shorter time to local recurrences and disease-specific deaths (P=0.03 and 0.01, respectively). This study demonstrated that QMSP of hypermethylated promoters in surgical margins predicted all the local recurrences in our series of HNSCC patients. We have also identified hypermethylation non-informative tumours as an independent predictor for the development of DSEs.