ABSTRACT
The discovery of kinase domain mutations in the epidermal growth factor receptor gene (EGFR) in never-smoker patients, associated with an increased sensitivity to tyrosine kinase inhibitors (TKIs) such as gefitinib or erlotinib, has been one of the most relevant findings ever in non-small cell lung carcinomas (NSCLC). Since treatment with TKIs has furthermore shown a clinical benefit in head and neck squamous cell carcinoma (HNSCC) patients, we hypothesized that these mutations could also be present in this neoplasia. Current studies looking for EGFR mutations in HNSCC are limited and results are still controversial. In this work, we screened for EGFR tyrosine kinase mutations in tumour DNA obtained from 31 Spanish patients with HNSCC by PCR-single-strand conformational polymorphism analysis. None of the patients displayed a somatic EGFR mutation, previously described in NSCLC, but other DNA sequence variations were found in 9 of 31 HNSCC patients. Accordingly, activating EGFR mutations in HNSCC patients seem to be a rare event in Spanish patients, suggesting that there is little room for the administration of TKIs in HNSCC based on the presence of these mutations. Additional investigations about EGFR amplification are indicated to establish a potential relationship between EGFR overexpression and the response to anti-EGFR therapies.
Subject(s)
Carcinoma, Squamous Cell/genetics , ErbB Receptors/chemistry , Genes, erbB-1/genetics , Head and Neck Neoplasms/genetics , Neoplasm Proteins/chemistry , Aged , Carcinoma, Squamous Cell/enzymology , Carcinoma, Squamous Cell/epidemiology , DNA Mutational Analysis , DNA, Neoplasm/genetics , ErbB Receptors/antagonists & inhibitors , Head and Neck Neoplasms/enzymology , Head and Neck Neoplasms/epidemiology , Humans , Laryngeal Neoplasms/enzymology , Laryngeal Neoplasms/epidemiology , Laryngeal Neoplasms/genetics , Male , Middle Aged , Mouth Neoplasms/enzymology , Mouth Neoplasms/epidemiology , Mouth Neoplasms/genetics , Neoplasm Proteins/antagonists & inhibitors , Pharyngeal Neoplasms/enzymology , Pharyngeal Neoplasms/epidemiology , Pharyngeal Neoplasms/genetics , Polymorphism, Single-Stranded Conformational , Protein Kinase Inhibitors/therapeutic use , Smoking/epidemiology , Smoking/genetics , Spain/epidemiologyABSTRACT
Serum levels of the soluble epidermal growth factor receptor (sEGFR) and its ligands epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha) and amphiregulin (AR) were measured in healthy donors and patients with non-small cell lung cancer (NSCLC) and head and neck carcinoma (HNC). In NSCLC, we found sEGFR and EGF levels significantly lowered in patients with respect to healthy donors. In HNC patients, significantly diminished levels were found in the case of sEGFR, EGF and also AR. In both malignancies, no significant association was found between the serum levels of the molecules and the patients' gender, age or smoking habit. Only a significant association was found between the decrease of sEGFR and the absence of distant metastasis in NSCLC and the tumour stage in HNC. The most interesting result was that combining sEGFR and EGF, sensitivities of 88% in NSCLC and 100% in HNC were reached without losing specificity (97.8% in both cases). The use of discriminant analysis and logistic regression improved the sensitivity for NSCLC and the specificity for HNC. These data demonstrate a potentially interesting value of the serum levels of sEGFR and EGF, especially when combined, as markers for NSCLC and HNC.
