Mutation analysis of genes in the EGFR pathway in Head and Neck cancer patients: implications for anti-EGFR treatment response

BMC Research Notes

Marc Baay⁶  Filip Lardon⁶  Patrick Pauwels²  Marc Peeters³  Jan B Vermorken³  Mark Kockx¹  Danielle Van den Weyngaert⁵  Carl Van Laer⁴  Pol Specenier³  An Wouters⁶  Vanessa Deschoolmeester⁶  Isabelle Vanden Bempt¹  Christine Weyn⁶  Carolien Boeckx⁶ 

[1] HistoGeneX, Berchem, Belgium;Department of Pathology, Antwerp University Hospital, Edegem, Belgium;Department of Medical Oncology, Antwerp University Hospital, Edegem, Belgium;Department of Otolaryngology, Antwerp University Hospital, Edegem, Belgium;Department of Radiation Therapy, Antwerp University Hospital, Edegem, Belgium;Center for Oncological Research (CORE) Antwerp, Laboratory of Cancer Research and Clinical Oncology, University of Antwerp, Wilrijk, Belgium

关键词: HPV;    EGFR tyrosine kinase mutations;    EGFRvIII mutations;    KRAS mutations;    Resistance;    Cetuximab;    EGFR inhibitors;    Head neck squamous cell carcinoma;   

Others  :  1132586
DOI  :  10.1186/1756-0500-7-337

 received in 2014-03-23, accepted in 2014-05-29,  发布年份 2014

【 摘 要 】

Background

Targeted therapy against the Epidermal Growth Factor Receptor (EGFR) is among the most promising molecular therapeutics for Head and Neck Squamous Cell Carcinoma (HNSCC). However, drug resistance limits the clinical efficacy of anti-EGFR monoclonal antibodies and no predictive biomarker has entered the clinic yet.

Methods

A retrospective clinical study was performed utilizing pathological specimens from 52 newly diagnosed HNSCC patients. These patients were screened for mutations in EGFR and KRAS. Tyrosine kinase mutations in EGFR and KRAS mutations were evaluated by high resolution melting analysis (HRMA), whereas EGFRvIII was determined using one-step real-time PCR. Finally, patient samples were screened for HPV-DNA by GP5+/6+ PCR. Survival analysis was performed using Kaplan-Meier analysis and significance was calculated using log-rank statistic.

Results

In our study population no EGFRvIII mutations were present. However, two silent mutations were found; T785T in exon 20 and R836R in exon 21 of the EGFR gene. Additionally, HRMA revealed an abnormal KRAS melting pattern in 7.0% of the samples. However, the KRAS StripAssay could confirm only one sample with a G12S mutation and none of these samples could be confirmed by direct sequencing. HPV DNA was present in 3/25 larynx and 9/27 oropharynx tumors.

Conclusion

The low rate of EGFR and KRAS mutations in this Belgian HNSCC population suggests that these genes will probably not play a major role in predicting response to anti-EGFR therapy in HNSCC. Hence, other predictive markers need to be discovered in order to optimize EGFR targeting therapy.

【 授权许可】

   
2014 Boeckx et al.; licensee BioMed Central Ltd.

【 图 表 】

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