EGFR protein overexpression and gene copy number increases in oral tongue squamous cell carcinoma
Introduction
Oral tongue squamous cell carcinomas (OTSCCs) are associated with increasing incidence and poor prognosis.1 Deeper understanding of the molecular behaviour of the tumour may improve patient outcome. New promising therapeutic agents targeting epidermal growth factor receptor (EGFR) have been developed but clinical information concerning EGFR status in OTSCC is limited.
Epidermal growth factor receptor (EGFR) is a tyrosine kinase (TK) receptor known to be associated with radiation resistance and prognosis in head and neck squamous cell carcinoma (HNSCC).2, 3 Overexpression of EGFR is seen in approximately 90% of head and neck cancers making it an interesting target for therapy.4, 5 EGFR inhibitors, one being C225 (cetuximab), have shown promising radiosensitivity enhancement with amplification of radiation-induced apoptosis in tumour specimens.6 These studies are highly supportive that EGFR might provide a radiosensitising route for OTSCC patients.
This study aimed to investigate EGFR status using immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH) in patients with OTSCC. We investigated the association between EGFR IHC and FISH. In addition, we evaluated whether EGFR protein expression and/or high gene copy numbers, ⩾four gene copies, were associated with tumour progression, treatment prediction of preoperative radiotherapy and prognosis in OTSCC.
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Materials and methods
We obtained 78 formalin-fixed, paraffin-embedded biopsy specimens with histopathologically confirmed OTSCC (UICC Stages I–IV) treated at the Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Karolinska University Hospital (Stockholm, Sweden) from January 2000 to December 2004. Clinical information, including age, tumour grade, treatment modality, treatment response and follow-up, was retrieved from medical records (Table 1). Each patient had a minimum follow-up time of at least 36
Results
EGFR protein expression determined by IHC showed that all tumours were positively stained for EGFR (Table 1). EGFR protein expression was categorised as intense in 72% and weak in 5% of patients, which is illustrated in Fig. 1A and B.
FISH analyses were performed on interphase cells from 65 OTSCC patients. Fifty-four percent (35 out of 65) of OTSCCs were FISH positive and had high gene copy numbers, i.e. ⩾four gene copy numbers (Table 1). In the positive group, there were 20 tumours with
Discussion
We investigated EGFR protein expression and gene copy number variation and its association with tumour progression, treatment prediction of preoperative radiotherapy and prognosis in OTSCC. We found that EGFR gene copy number significantly correlated with EGFR protein expression levels. Tumours that responded to radiotherapy showed less EGFR protein expression and the same trend was seen for EGFR gene copy number. Finally non-smokers had significantly higher EGFR protein expression and higher
Conflict of interest statement
None declared.
Acknowledgements
This work was supported by the Swedish Cancer Society (Cancerfonden), the Cancer Society of Stockholm (Cancerföreningen), Laryngfonden, Karolinska Institutet and the Intramural Research Programme of the NIH, National Cancer Institute. We gratefully thank Ann Olsson and Margaretha Waern for excellent technical assistance.
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These authors contributed equally to this work.