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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Except in developed countries, the incidence of lung cancer notably in women and non-smokers is rising in most parts of the world. Here, we report two children diagnosed with pulmonary adenocarcinoma at a very early age. Interestingly, both showed negative EGFR mutation despite their ethnicity, histology, never smoking status and early age. Furthermore, one had preceding pulmonary tuberculosis. In the literature, the possible association of pulmonary tuberculosis and adenocarcinoma of lung especially in non-smokers has long been debated. The two children, by far the youngest with EGFR negative adenocarcinoma of lung, form the basis of this report.
Lung Cancer 2008 Aug
PMID:Adenocarcinoma of lung in never smoked children. 1839 48

The management of advanced non-small cell lung cancer (NSCLC) has progressed over the last 3 decades due to advances in chemotherapeutic drugs and targeted agents improving survival and quality of life. In particular erlotinib, an orally available human epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor advancing through clinical trials for the treatment of various human malignancies in a large placebo-controlled phase III study, has shown a significantly better OS vs. placebo suggesting its potential benefits in third line and possibly in second line treatments. The association of erlotinib with ionizing radiation has been recently published showing an enhancing antitumor activity and good tolerance. No information are available on side effects when erlotinib is associated with abdominal hypofractionated radiotherapy although diarrhoea is the most known side effect dose-limiting toxicity when the abdomen is treated. Here we report a fatal acute diarrhoea in a metastatic NSCLC patient taking erlotinib during abdominal hypofractionated radiotherapy for metastatic spinal cord compression (MSCC).
Lung Cancer 2008 Aug
PMID:Acute and fatal diarrhoea after erlotinib plus abdominal palliative hypofractionated radiotherapy in a metastatic non-small cell lung cancer patient: a case report. 1844 70

This study was conducted to evaluate the prevalence of EGFR and KIT mutations in thymomas and thymic carcinomas as a means of exploring the potential for molecularly targeted therapy with tyrosine kinase inhibitors. Genomic DNA was isolated from 41 paraffin-embedded tumor samples obtained from 24 thymomas and 17 thymic carcinomas. EGFR exons 18, 19, and 21, and KIT exons 9, 11, 13, and 17, were analyzed for mutations by PCR and direct sequencing. Protein expression of EGFR and KIT was evaluated immunohistochemically. EGFR mutations were detected in 2 of 20 thymomas, but not in any of the thymic carcinomas. All of the EGFR mutations detected were missense mutations (L858R and G863D) in exon 21. EGFR protein was expressed in 71% of the thymomas and 53% of the thymic carcinomas. The mutational analysis of KIT revealed only a missense mutation (L576P) in exon 11 of one thymic carcinoma. KIT protein was expressed in 88% of the thymic carcinomas and 0% of the thymomas. The results of this study indicate that EGFR and KIT mutations in thymomas and thymic carcinomas are rare, but that many of the tumors express EGFR or KIT protein.
Lung Cancer 2008 Dec
PMID:Mutational status of EGFR and KIT in thymoma and thymic carcinoma. 1844 88

Recent years have brought tremendous progress in the development of genomic and proteomic platforms to study cancer biology. Tests based on these platforms are helpful in early diagnosis, prognosis, and prediction of treatment benefit. Molecular studies performed on minimally invasive material (plasma, sputum) from individuals participating in longitudinal or case-control studies have approximately 70%-90% sensitivity and specificity to detect lung cancer. In operable non-small-cell lung cancer, genomic and proteomic studies yield better prognostic information than pathologic staging. There are several examples of successful identification of predictive assays for benefit from chemotherapy (ERCC1, RRM1, p27Kip1, and p53 expression) or targeted therapies (epidermal growth factor receptor [EGFR] gene copy number, EGFR activating mutations, EGFR protein expression, serum proteomic profile). These markers should be prospectively tested in clinical studies before they can be routinely used in the clinic.
Clin Lung Cancer 2008 Mar
PMID:Advances in genomic and proteomic studies of non-small-cell lung cancer: clinical and translational research perspective. 1850 Oct 93

Epithelial to mesenchymal transition (EMT) has been reported to be related with reduced sensitivity to EGFR tyrosine kinase (EGFR-TK) inhibitors. We performed this study to investigate whether this phenomenon would play a role in acquired resistance to gefitinib. In this study, we established a gefitinib-resistant subline (A549/GR), which was derived from the parental A549 cell line by chronic, repeated exposure to gefitinib. Compared with the A549 cells, the A549/GR cells were approximately 7.7-fold more resistant to gefitinib and they showed the cross-resistance against other EGFR-TK inhibitors, including CL-387,758, erlotinib and ZD6478. Phenotypic changes such as a spindle-cell shape and increased pseudopodia formation suggesting EMT was present in the A549/GR cells. These changes were accompanied by a decrease of E-cadherin and an increase of vimentin, which is a mesenchymal marker. In addition, the ability of invasion and migration was increased in the A549/GR cells. TGF-beta1 treatment for 72 h also induced EMT in the A549 cells and this transition led to resistance to gefitinib. Conversely, this was reversed through the removal of TGF-beta1. In conclusion, induction of EMT may contribute to the decreased efficacy of therapy in primary and acquired resistance to gefitinib.
Lung Cancer 2009 Feb
PMID:Epithelial to mesenchymal transition derived from repeated exposure to gefitinib determines the sensitivity to EGFR inhibitors in A549, a non-small cell lung cancer cell line. 1859 54

It has been suggested that a high EGFR gene copy number may be an indicator of good response to EGFR tyrosine kinase inhibitor therapy and a marker of poor prognosis in NSCLC. However, imaging features related to EGFR gene copy number status in adenocarcinoma are still unknown. We therefore retrospectively analyzed CT, FDG-PET, and histopathologic slides of surgical resected lung adenocarcinoma in 132 patients. Tumor characteristics on preoperative chest-CT, such as, GGO proportions, tumor diameters, and cavitation; FDG-PET SUV(max); and histopathologically determined differentiation degrees and tumor subtypes were evaluated. EGFR gene copy number status was categorized as FISH-positive or -negative. FISH-positivity was found in 53 patients (40.2%) and was significantly more frequent in tumors with a SUV(max)>7.0 (P=0.007). Furthermore, FISH-negativity was found to be more frequent in tumors with a GGO>50% (P=0.023) and diameter <15.5mm (P=0.006) on CT, or a well-differentiated histopathology (P=0.002). Moreover, the frequency of FISH-positivity increased as SUV(max) increased (P=0.0008) and as the proportion of GGO decreased (P=0.01). SUV(max)>7.0 was an independent predictor of FISH-positive results (odds ratio, 3.941; 95% CI, 1.691-9.182; P=0.01). In conclusion, a high SUV(max) on FDG-PET was significantly related to FISH-positive results. A high proportion of GGO, small tumor diameter on CT, and a well-differentiated histopathology were more frequent in FISH-negative adenocarcinomas.
Lung Cancer 2009 May
PMID:EGFR gene copy number in adenocarcinoma of the lung by FISH analysis: investigation of significantly related factors on CT, FDG-PET, and histopathology. 1881 24

The incidence of several extracolonic tumors, such as duodenal carcinoma, is higher in familial adenomatous polyposis (FAP) patients than in the general population, but there is little information about lung carcinoma in FAP. A 43-year-old woman presented with a lung tumor 17 years after total colectomy for FAP. Pathohistological analysis of the lung tumor demonstrated mixed adenocarcinoma consisting of a papillary adenocarcinoma component and a bronchioloalveolar carcinoma component. Sequencing analysis indicated a germline APC mutation from TCA to TGA (stop) at codon 1110, but no pathogenic germline MYH mutations. The other APC allele in the lung carcinoma was not inactivated by somatic mutations, promoter methylation, or chromosomal deletion. No somatic mutations in any of the coding regions of the p53 gene or in the mutation hot spot regions of the K-ras or EGFR genes were detected in the carcinoma. Amplification, however, of three chromosome regions, 5p, 8q, and 12q14-12q21, was identified in the carcinoma on genome-wide high-resolution single-nucleotide polymorphism (SNP) microarray. The present results suggest that the chromosomal copy number alterations detected on SNP microarray were involved in the carcinogenesis of the adenocarcinoma of the lung in the present FAP patient.
 ...
PMID:Characterization of adenocarcinoma of the lung in a familial adenomatous polyposis patient. 1884 36

Mucoepidermoid carcinoma (MEC) of the lung needs to be carefully distinguished from other lung tumors with similar features, particularly from adenosquamous carcinoma, this latter tumor frequently showing EGFR mutations. In contrast with the data reported by Han et al in the last July issue of Lung Cancer, neither EGFR nor K-RAS mutations were observed in MEC from caucasian patients.
Lung Cancer 2009 Jan
PMID:Mucoepidermoid carcinoma of the lung, response to EGFR inhibitors, EGFR and K-RAS mutations, and differential diagnosis. 1819 72

EGFR (ErbB1) and ErbB2 receptors stimulate several intracellular signaling pathways in non-small-cell lung cancer (NSCLC). Adenocarcinomas (AC) and squamous cell carcinomas (SCC) are NSCLC subtypes with distinct clinico-pathological features, and responses to ErbB-targeted inhibitors treatment. To evaluate the causes of these differences, tissue microarrays with samples from NSCLC patients (189 AC and 56 SCC) were used to study EGFR and ErbB2 expression and phospho-activation of ERK1/2, AKT, STAT3 and SRC ErbB-mediators by immunohistochemistry and Western blot, and EGFR and ErbB2 gene amplification by FISH. EGFR expression was higher in SCC than in AC (P<0.001), while ErbB2 showed similar low levels. Phosphorylated (p) ERK, pAKT, pSTAT3 and pSRC levels were prevalent in AC (P< or =0.002). EGFR levels and signaling mediators activation were differentially associated with each of the pathologies. Whereas in AC the expression and amplification of EGFR were linked to AKT activation (P< or =0.050), in SCC its expression was correlated with pSTAT3 (P=0.024). In addition, pSTAT3 was correlated with pERK and pAKT only in AC (P< or =0.045). Biomarker levels were also differentially associated with the clinico-pathologic variables. In AC, EGFR and pSRC increasing scores correlated with female sex and the smoking habit (P< or =0.008), while ErbB2 amplification increased with advanced age and tumor stage (P< or =0.047), and pERK1/2 and pSTAT3 levels correlated with early tumor stage (P< or =0.045). In SCC, EGFR amplification was stronger in younger patients (P=0.013), pERK1/2 in the older ones (P=0.050), and pSTAT3 amplification was stronger in women (P=0.001). These data support that AC and SCC lung tumors are distinct entities at the molecular level, and that their signaling status in combination with their clinico-pathologic variables may be considered for differential targeted therapies.
Lung Cancer 2009 Jul
PMID:Differential ErbB receptor expression and intracellular signaling activity in lung adenocarcinomas and squamous cell carcinomas. 1904 92

We examined the methylation status in 100 specimens of lung adenocarcinomas measuring 2cm or less and with bronchioloalveolar carcinoma (BAC) components (Noguchi types A-C) and then compared the methylation status between noninvasive tumors (Noguchi type A or B) and invasive tumors (Noguchi type C). Methylation-specific PCR was used to determine the methylation statuses of p16(INK4a), RASSF1A, CDH13, RARbeta, and Cyclin D2. The methylation index that was regarded as representing the degree of methylation was calculated. We also determined the mutational statuses of EGFR exons 19 and 21 using a PCR-based method. A multivariate analysis showed that the aberrant methylation of p16(INK4a), RASSF1A, and CDH13 was significantly more frequent in invasive tumors than in noninvasive tumors [p16(INK4a), 36.5% versus (vs.) 8.3%, P=0.0023; RASSF1A, 46.2% vs. 14.6%, P=0.0012; CDH13, 42.3% vs. 10.4%, P=0.0006]. The methylation index was significantly higher in invasive tumors than in noninvasive tumors (P=0.004). The methylation of p16(INK4a) was significantly more frequent in EGFR wild-type tumors than in EGFR mutant tumors (P=0.021). Our results indicate the involvement of epigenetic alterations in the progression of adenocarcinoma with BAC components.
Lung Cancer 2009 Sep
PMID:DNA methylation in small lung adenocarcinoma with bronchioloalveolar carcinoma components. 1914 41


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