ABSTRACT
<p><b>OBJECTIVE</b>To investigate gene mutations of epidermal growth factor receptor (EGFR) and K-ras in Chinese patients with non-small cell lung cancer (NSCLC) and its clinicopathological significance, and to analyze the correlation between these mutations and tumor response to erlotinib treatment.</p><p><b>METHODS</b>Mutations of exons 18, 19, 20 and 21 of the EGFR and codons 12, 13 of the K-ras in 301 cases of NSCLC were detected by PCR-amplification and gene sequencing. The relationship between the mutations and clinicopathological characteristics of the 301 patients was analyzed.</p><p><b>RESULTS</b>EGFR mutations were present in 32.9% (99/301) of the samples: 3 mutation in exon 18, 59 in exon 19, 2 in exon 20, and 35 in exon 21. Mutations of K-ras were present in 4.7% (14/301) of the samples: 13 in codon 12 and 1 in codon 13. EGFR mutations were never found in tumors with K-ras mutations, suggesting a mutually exclusive relationship. EGFR mutations were more common in adenocarcinomas, non-smokers and females. Seven out of 10 erlotinib-treated patients with disease control carried EGFR mutation.</p><p><b>CONCLUSION</b>The frequency of EGFR mutation in Chinese NSCLC patients is higher than that in Westerners, but the frequency of K-ras mutation is quite opposite. Combined detection of EGFR gene and K-ras gene mutation may help clinicians to choose patients who may gain benefit from EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment, and to predict their response to erlotinib treatment and prognosis.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Adenocarcinoma , Drug Therapy , Genetics , Pathology , Asian People , Carcinoma, Non-Small-Cell Lung , Drug Therapy , Genetics , Pathology , Carcinoma, Squamous Cell , Drug Therapy , Genetics , Pathology , Codon , Erlotinib Hydrochloride , Exons , Genes, erbB-1 , Genes, ras , Lung Neoplasms , Drug Therapy , Genetics , Pathology , Mutation , Protein Kinase Inhibitors , Therapeutic Uses , Proto-Oncogene Proteins , Genetics , Proto-Oncogene Proteins p21(ras) , Quinazolines , Therapeutic Uses , ErbB Receptors , Genetics , Sex Factors , Smoking , ras Proteins , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To investigate the mRNA and proten expression of coxsackievirus and adenovirus receptor (CAR) in the corresponding normal lung tissue, para-neoplastic tissue and lung cancer tissue, and the correlation of CAR expression with the carcinogenesis as well as the expression difference in various clinicopathologic parameters.</p><p><b>METHODS</b>The expression of CAR mRNA and protein in the samples from 32 lung cancer patients was determined by RT-PCR and Western blot, respectively.</p><p><b>RESULTS</b>The expression level of CAR mRNA and protein in normal lung tissue, paraneoplastic tissue and cancer tissue were 1.000 +/- 0.012, 1.048 +/- 0.035, 1.282 +/- 0.072, and 0.902 +/- 0.038, 0.944 +/- 0.042, 1.08 +/- 0.052, respectively, with a statistical significance among the groups (P = 0.022, P = 0.007, P = 0.009, P = 0.027). There was a statistically significant positive correlation between expression of CAR mRNA and that of CAR protein (r = 0.448, P = 0.026). The expression levels of CAR were significantly different among different pathological types (P = 0.012), with a high level of CAR in all 7 bronchiolo-alveolar carcinoma (BAC, P = 0.029). However, there was no statistical significance in other clinicopathologic parameters (P > 0.05), including gender, age, smoking or not, tumor size, with or without lymph node metastasis and TNM stage.</p><p><b>CONCLUSION</b>The expression of CAR mRNA and protein in cancer tissue samples are significantly higher than that in the normal and paraneoplastic samples, indicating that CAR might play a crucial role in the carcinogenesis. It may become a new potential prognostic marker for lung cancer patients.</p>