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NSCLC Cases (nsclc + case)
Selected AbstractsUsefulness of EGFR mutation screening in pleural fluid to predict the clinical outcome of gefitinib treated patients with lung cancerINTERNATIONAL JOURNAL OF CANCER, Issue 10 2006Junichi Soh Abstract The importance of epidermal growth factor receptor (EGFR) gene mutation has been recognized in nonsmall cell lung cancer (NSCLC), requiring the standardization of mutation screening system including the kind of samples. Here, we examined the EGFR mutation status in 61 pleural fluid samples from NSCLC cases using direct sequencing, nonenriched PCR, mutant-enriched PCR and peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp assay. The mutant-enriched PCR assay detected 16 mutant cases. Among them, the nonenriched PCR assay failed to detect 3 mutant cases. Regarding the discrepancy between mutant-enriched PCR and PNA-LNA PCR clamp assays, 3 cases of exon19-deletions were detected only by mutant-enriched PCR assay and no difference at the L858R mutation. There was no difference in results between direct sequencing and nonenriched PCR assay. We also correlated the EGFR mutation with clinical outcome of gefitinib-treated 29 cases. EGFR mutations were present in 10 cases, revealing 7 partial response and 3 no change (NC). In EGFR wild-type cases, 10 revealed NC and 9 progressive disease. The responders were significantly more frequent among the EGFR mutant cases than among the wild-type (p < 0.0001). Overall survival (p = 0.0092) and progression-free survival (p = 0.018) were significantly longer among the EGFR mutant cases than among the wild-type. In summary, we evaluated the utility of EGFR mutation screening in pleural fluid using 4 assays that showed some discrepancies arising from the designs of the assays. As clinical importance, the EGFR mutation status in pleural fluid can be a biomarker for the favorable outcome of gefitinib-treated NSCLC cases. © 2006 Wiley-Liss, Inc. [source] Co-overexpression of fibroblast growth factor 3 and epidermal growth factor receptor is correlated with the development of nonsmall cell lung carcinomaCANCER, Issue 1 2006Amy L.S. Tai M.Phil. Abstract BACKGROUND Lung cancer is a prevalent cancer with a poor prognosis. To develop a useful in vitro cell model, a cell line of lung squamous cell carcinoma (SCC-35) was established. METHODS The SCC-35 cell was characterized by comparative genomic hybridization (CGH) and spectral karyotyping (SKY). Chromosome microdissection, fluorescence in situ hybridization (FISH), and Southern and Northern blots analyses were used to study target genes. RESULTS Two amplicons were found at chromosomes 7p12 and 11q13. Amplification and overexpression of epidermal growth factor receptor (EGFR) at 7p12 and fibroblast growth factor 3 (FGF3) at 11q13 were found. To understand the correlation between these two genes in nonsmall cell lung carcinoma (NSCLC) more comprehensively, overexpression of FGF3 and EGFR was investigated by immunohistochemistry with a tissue microarray containing 406 NSCLC samples. Cytoplasmic overexpression of FGF3 and EGFR was detected in 61% and 69% NSCLC cases, respectively. More interestingly, a significant correlation between overexpression of FGF3 and EGFR was found in NSCLC. CONCLUSION These results suggest that co-overexpression of FGF3 and EGFR may play an important role in the pathogenesis of lung carcinoma. Cancer 2006. © 2005 American Cancer Society. [source] Hypermethylation of FHIT as a prognostic marker in nonsmall cell lung carcinomaCANCER, Issue 7 2004Riichiroh Maruyama M.D. Abstract BACKGROUND Methylation of CpG islands in the promoter and upstream coding regions has been identified as a mechanism for transcriptional inactivation of tumor suppressor genes. The purpose of the current study was to determine the correlation between the aberrant promoter methylation of multiple genes and survival in patients with nonsmall cell lung carcinoma (NSCLC). METHODS The methylation status of nine genes was determined in 124 surgically resected NSCLC cases using methylation-specific polymerase chain reaction. RESULTS The methylation frequencies of the genes tested in NSCLC specimens were 52% for E-cadherin (CDH1), 41% for RAS association domain family protein (RASSF1A), 38% for fragile histidine triad (FHIT) and adenomatous polyposis coli (APC), 27% for retinoic acid receptor beta (RAR,) and H-cadherin (CDH13), 20% for p16INK4A, 0.8% for O6 -methylguanine-DNA-methyltransferase (MGMT), and 0% for glutathione S-transferase P1 (GSTP1). The survival of the patients with FHIT methylation-positive tumors was found to be significantly shorter than that for those patients with methylation-negative tumors (P = 0.03), even in those patients with International Union Against Cancer TNM Stage I or Stage II disease (P = 0.007). In contrast, there were no significant survival differences noted between the methylation-positive and methylation-negative tumors for the other genes tested. In addition, based on multivariate analyses, FHIT methylation-positive status was found to be independently associated with poor survival (P = 0.046) and disease stage (P < 0.0001). CONCLUSIONS The results of the current study suggest that methylation of FHIT is a useful biomarker of biologically aggressive disease in patients with NSCLC. Cancer 2004;100:1472,7. © 2004 American Cancer Society. [source] Non-solid oncogenes in solid tumors: EML4,ALK fusion genes in lung cancerCANCER SCIENCE, Issue 12 2008Hiroyuki Mano It is generally accepted that recurrent chromosome translocations play a major role in the molecular pathogenesis of hematological malignancies but not of solid tumors. However, chromosome translocations involving the e26 transformation-specific sequence transcription factor loci have been demonstrated recently in many prostate cancer cases. Furthermore, through a functional screening with retroviral cDNA expression libraries, we have discovered the fusion-type protein tyrosine kinase echinoderm microtubule-associated protein like-4 (EML4),anaplastic lymphoma kinase (ALK) in non-small cell lung cancer (NSCLC) specimens. A recurrent chromosome translocation, inv(2)(p21p23), in NSCLC generates fused mRNA encoding the amino-terminal half of EML4 ligated to the intracellular region of the receptor-type protein tyrosine kinase ALK. EML4,ALK oligomerizes constitutively in cells through the coiled coil domain within the EML4 region, and becomes activated to exert a marked oncogenicity both in vitro and in vivo. Break and fusion points within the EML4 locus may diverge in NSCLC cells to generate various isoforms of EML4,ALK, which may constitute ~5% of NSCLC cases, at least in the Asian ethnic group. In the present review I summarize how detection of EML4,ALK cDNA may become a sensitive diagnostic means for NSCLC cases that are positive for the fusion gene, and discuss whether suppression of ALK enzymatic activity could be an effective treatment strategy against this intractable disorder. (Cancer Sci 2008; 99: 2349,2355) [source] | ||||||||||