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>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Adenocarcinoma, Bronchiolo-Alveolar , Metabolism , Pathology , Biomarkers, Tumor , Metabolism , Blotting, Western , Carcinoma, Non-Small-Cell Lung , Metabolism , Pathology , Coxsackie and Adenovirus Receptor-Like Membrane Protein , Lung , Metabolism , Lung Neoplasms , Metabolism , Pathology , Lymphatic Metastasis , Prognosis , RNA, Messenger , Metabolism , Receptors, Virus , Genetics , Metabolism , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
<p><b>OBJECTIVE</b>To assess the effect of endostatin on growth and neoplastic angiogenesis in transplanted human lung adenocarcinoma Calu-6 tumor in nude mice.</p><p><b>METHODS</b>To treat Calu-6 tumor-bearing mice with endostatin at different doses, and to record the changes of the tumor size. The expressions of survivin, VEGF, COX-2 and MVD in tumor tissue were examined by immunohistochemistry staining, circulating endothelial cells (CECs) by flow cytometry and mRNA of CD146 and CD105 by RT-PCR and real-time PCR.</p><p><b>RESULTS</b>After endostatin treatment, the tumor size was conspicuously shrunk, and the expressions of survivin, COX-2 and VEGF protein and MVD in tumor tissue decreased concomitantly with the significant difference between each of trial groups and control group (all P < 0.05). Both CECs and mRNA of CD146 and CD105 diminished remarkably. A positive correlation between both exhibition and change of amount of activated CECs and survivin, VEGF expression and MVD count in tumor tissue was found.</p><p><b>CONCLUSION</b>Endostatin can decrease the expression of survivin, COX-2, VEGF and MVD, and to inhibit the growth of transplanted tumor. Activated CECs may probably serve as an ideal marker to predict the efficacy and prognosis of anti-angiogenesis therapy.</p>
Subject(s)
Animals , Female , Humans , Mice , Adenocarcinoma , Pathology , Angiogenesis Inhibitors , Pharmacology , Antigens, CD , Metabolism , Antineoplastic Agents , Pharmacology , CD146 Antigen , Metabolism , Cell Line, Tumor , Cyclooxygenase 2 , Metabolism , Dose-Response Relationship, Drug , Endoglin , Endostatins , Pharmacology , Endothelial Cells , Pathology , Inhibitor of Apoptosis Proteins , Lung Neoplasms , Metabolism , Pathology , Mice, Inbred BALB C , Mice, Nude , Microtubule-Associated Proteins , Metabolism , Microvessels , Pathology , Neoplasm Transplantation , RNA, Messenger , Metabolism , Random Allocation , Receptors, Cell Surface , Metabolism , Tumor Burden , Vascular Endothelial Growth Factor A , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the pathological diagnosis, surgical treatment and prognostic factors of gastrointestinal stromal tumors (GISTs).</p><p><b>METHODS</b>The clinicopathological data of operated 96 patients with GISTs were analyzed retrospectively. Expression of CD117, CD34, SMA and S-100 was determined by immunohistochemical methods.</p><p><b>RESULTS</b>Expression of CD117, CD34, SMA and S-100 was 79.2% (76/96), 58.3% (56/96), 35.4% (34/96) and 9.4% (9/96). Benign tumor 23 and malignant 73. Of the malignant, the omentum was resected in 39 and the rest remained, of which the recurrent and metastatic rates were 5.1% and 26.5% (P < 0.05). The safety margin between the normal intestine and tumor was > 5 cm in 46 patients; while in the other 27 patients, it was < 5 cm. The recurrent and metastatic rates were 6.5% and 29.6% (P < 0.05), respectively. The 5-year survival rates of benign and malignant GISTs were 91.5% and 57.3% (P < 0.05).</p><p><b>CONCLUSION</b>The application of immunohistochemical markers CD117 and CD34 are supplementary to pathological diagnosis. The adapting of rational primary treatment, including complete tumor resection and prophylactic omentectomy, is able to reduce the recurrence of GISTs.</p>