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

Two human cancer cell lines were established from metastatic lesions of an adenocarcinoma (RAL) and a squamous cell (CAEP) carcinoma of the lung. The clinical histories of the patients from whom the cell lines were derived are reported. The lines were maintained in continuous culture with doubling times of 65 (RAL) and 50 (CAEP) hours. The RAL and CAEP cell lines, whose morphology and ultrastructural features are presented, showed extensively rearranged karyotypes with modal number of 85 (RAL) and 98 (CAEP). In particular, chromosome 2 pentasomy and several clonal markers were evident in the RAL cells, whereas a telomeric deletion of chromosome 1, del (1)(q32), was observed in the CAEP cells. The morphologic data were confirmed by high expression of specific antigens for each histotype. A marked positivity of the neuron-specific enolase (NSE) levels was evident by immunoenzymatic assays in the cell lines cytosol with respect to those present in the respective patient's sera. No amplification or rearrangements were evident in the CMYC, LMYC, NMYC, INT-2, ERBB2, HRAS, KRAS, MOS, HST-1 genes by Southern blotting analysis in each cell line. Point mutations in exon 1 of KRAS and in exon 7 of TP53 were evident by polymerase chain reaction (PCR)-DNA sequencing in the RAL cell line, whereas no alterations were present in the HRAS and RB genes. The four genes studied did not show point mutations in the CAEP cell line. The RAL cell line was resistant to all the drugs tested, whereas the CAEP cells were sensitive to vinblastine. These cell lines may represent useful experimental models to investigate lung cancer biology and anticancer drug response.
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PMID:Molecular and biological features of two new human squamous and adenocarcinoma of the lung cell lines. 980 28

The epidermal growth factor receptor (EGFR) gene has recently been reported to be mutated in a subset of non-small cell lung cancers (NSCLC), with the mutations being correlated with the patients' drug sensitivity to gefitinib, an EGFR kinase inhibitor. In this study, we searched for EGFR mutations in patients with lung cancer using primary tumor specimens obtained at initial surgery and examined whether their recurrent tumors showed a response to gefitinib depending on the presence of the activating mutation. Among 12 lung cancers that were treated with gefitinib after recurrence, we found that all four tumors which showed a response to gefitinib had an activating mutation in EGFR, whereas none of the remaining eight tumors had a mutation. Southern blot analysis showed that two of the four responsive tumors had the EGFR gene amplification. We also examined another 73 NSCLC specimens (47 males and 26 females; 53 adenocarcinomas and 20 non-adenocarcinomas) which were not treated with gefitinib to determine whether NSCLCs with an EGFR mutation have different clinicopathological properties and/or unique genetic alterations of the other cancer-associated genes. We found that 13 (18%) of 73 tumors had a mutation of the EGFR gene, with the most being detected in female adenocarcinomas. Comparing the alterations in KRAS and P53 with the EGFR mutation, we found that 10 tumors with the KRAS mutation did not have an EGFR mutation, suggesting that each mutation occurs exclusively during the development of lung cancer. These results suggest that the mutation analysis of the EGFR gene using the specimens obtained at surgery might be useful in selecting the appropriate treatment(s) for recurrent lung cancer patients.
Lung Cancer 2005 Dec
PMID:Mutations of epidermal growth factor receptor of non-small cell lung cancer were associated with sensitivity to gefitinib in recurrence after surgery. 1614 Apr 20

Biphasic pulmonary blastoma is a rare lung tumor with epithelial and mesenchymal components. Genetic alterations in this tumor are largely unknown, except for the presence of beta-catenin and p53 mutations and the absence of KRAS mutation. To understand the molecular process of histogenesis of this tumor, a whole genome allelic imbalance (AI) scanning using a high-resolution single nucleotide polymorphism array as well as mutational analysis of the p53, EGFR, KRAS and beta-catenin genes were performed against the epithelial and mesenchymal components in the primary tumor and a metastatic tumor in a case of pulmonary blastoma. AI at chromosome regions 14q24-q32 and 17p11-p13 and beta-catenin mutation were commonly detected in all tumors. On the other hand, AI at chromosome regions 3p11-p14 and 9p21-p24 and p53 mutation were detected only in the mesenchymal component in the primary tumor but not in the epithelial component in the primary tumor and the brain metastasis. Likewise, AI at chromosome regions 6p24-p25 and 6q14-q27 was detected in the epithelial component in the primary tumor and the brain metastasis but not in the mesenchymal component in the primary tumor. Furthermore, the genetic alterations detected in the metastatic tumor were completely the same as those in the epithelial component in the primary tumor, indicating that a tumor cell(s) in the epithelial component in the primary tumor selectively metastasized to the brain. These results indicate that this biphasic tumor is of monoclonal origin and the phenotypic heterogeneity of the tumor is due to the differences in the accumulated genetic alterations in each component of the tumor.
Lung Cancer 2007 Jul
PMID:Clonality and heterogeneity of pulmonary blastoma from the viewpoint of genetic alterations: a case report. 1735 Jan 38

In lung adenocarcinomas, genetic alterations of PTEN are relatively rare and little has been reported concerning the relationship between PTEN transcriptional level and clinicopathologic features or genetic changes. This study was conducted to gain insight into clinicopathologic correlations. The transcriptional levels of PTEN were examined using real time RT-PCR and analyzed for correlations with clinicopathologic features and the mutation status of EGFR and KRAS. After confirming significant correlation for PTEN levels between macrodissected and microdissected materials (p<0.01), macrodissected samples from 115 lung adenocarcinomas were examined. There were no significant difference between the PTEN levels, divided into three ranges, and the mutation status of EGFR or KRAS. Noteworthy clinicopathologic correlations between PTEN transcriptional up/down-regulation and young age (p=0.0081, 61.7+/-8.7years versus 66.1+/-8.1years), smoking (p=0.032) and less differentiated adenocarcinomas (p=0.013) were identified. Whereas male patients demonstrated no prognostic association with PTEN levels, female cases with up-regulated PTEN expression had significantly worse survival compared with those with normal PTEN levels (p=0.0027). This study revealed distinct clinicopathologic correlations with PTEN transcriptional up/down-regulation.
Lung Cancer 2007 Aug
PMID:Up-regulation of PTEN at the transcriptional level is an adverse prognostic factor in female lung adenocarcinomas. 1745 61

It has been proposed that reduced let-7 expression causes RAS expression and correlates with poor survival of lung cancer cases, but little is known about correlations with clinicopathologic features. In this study, we examined 15 early bronchioloalveolar carcinomas (BACs), usually considered as adenocarcinomas in situ, as well as 26 well-differentiated and 25 less-differentiated invasive adenocarcinomas, to assess the association between tumor progression and let-7 expression levels. Additionally, we investigated 47 invasive lung adenocarcinomas for EGFR and KRAS mutations and correlations with let-7 levels. Relative to the corresponding normal lung tissue, reduced let-7 expression was observed in 13 of 15 BACs (87%) and totally in 52 of the 66 adenocarcinomas (79%), suggesting a link with early occurrence in carcinogenesis. On classification of adenocarcinomas into two groups according to let-7 expression, no prognostic or genetic differences were observed. Interestingly, some differences between histological subtypes were observed, such as lower let-7 expression levels in acinar adenocarcinomas and mucinous BACs.
Lung Cancer 2007 Dec
PMID:let-7 microRNA expression is reduced in bronchioloalveolar carcinoma, a non-invasive carcinoma, and is not correlated with prognosis. 1839 92

Recent studies have reported that clinical response to epidermal growth factor receptor (EGFR) inhibitors is associated with somatic changes of EGFR in the advanced stage of lung cancer. However, there is no clear data demonstrating whether such molecular changes of EGFR per se can affect the clinical outcome of early stage cancer after surgical resection. DNA mutations of EGFR and KRAS were investigated in 71 adenocarcinoma patients who received surgical resection. Fluorescence in situ hybridization (FISH) of EGFR gene amplification was performed in 48 samples. We detected EGFR mutations in 25 patients (35.2%). EGFR mutation was more frequently found in cases with BAC features (13/22 (59.1%):13/49 (26.5%); p=0.008) and in non-smokers (19/41 (46.3%):7/30 (23.3%); p=0.047). However, the EGFR mutation was not associated with age, gender, or clinical stage. The amplification of EGFR copy was frequently observed in the female gender (12/29 (41.4%):3/19 (15.8%); p=0.061) and in the advanced stage (> or =Stage IIIA, 9/19 (47.4%):6/29 (20.7%); p=0.051). KRAS mutations were present in five patients (7.0%) and none of them showed EGFR mutation. KRAS mutations (p=0.000), male gender (p=0.001), absence of BAC feature (p=0.003), advanced stage (p=0.039), and smoking history (p=0.030) were poor prognostic factors for overall survival, whereas EGFR mutation (p=0.184) and amplification (p=0.756) were not. The presence of EGFR mutation was not a prognostic factor of the clinical outcome of early lung cancer after surgical resection. This result provides an important message for the protocol design of future trials of EGFR inhibitors in early lung cancer. As the KRAS mutation was a poor prognostic factor and it presents reciprocally with EGFR mutation, KRAS mutation should be investigated in such trials. DNA mutations of EGFR and KRAS were investigated in 71 adenocarcinoma patients who received surgical resection. Whereas KRAS mutation was a poor prognostic factor, EGFR mutation was not, and its presence per se did not affect the clinical outcome of early lung cancer after surgical resection.
Lung Cancer 2008 Jan
PMID:Molecular changes of epidermal growth factor receptor (EGFR) and KRAS and their impact on the clinical outcomes in surgically resected adenocarcinoma of the lung. 1790 85

The purpose of the present study was to establish accurate prognostic markers to predict the post-operative recurrence of stage I lung adenocarcinomas (ADC). One-hundred and ninety cases of stage I ADC were examined for KRAS mutations and Ki-67 expression, and their associations with disease recurrence were analyzed. KRAS-mutated cases showed a significantly higher risk of recurrence than cases without mutations (5-year disease-free survival (DFS) 61.0% vs. 85.8%, P=0.017: adjusted Hazard ratio (HR) 4.55, 95% Confidence Interval (CI) 1.61-12.82, P=0.004). Ki-67 high-expressers (labeling index >10%) also showed a higher risk of recurrence than low-expressers (5-year DFS 68.7% vs. 93.2%, P<0.001: adjusted HR 3.84, 95% CI 1.18-12.45, P=0.025). Ki-67 high-expressers with KRAS mutations showed an additional higher risk of recurrence compared to low-expressers without mutations (5-year DFS 37.5% vs. 93.3%, P<0.001: adjusted HR 16.82, 95% CI 3.77-74.98, P<0.001) and their 5-year DFS was nearly equivalent to that of stage II non-small cell lung cancer (NSCLC) in our facility (37.5% vs. 37.2% for stage II NSCLC, p=0.577). The combined use of KRAS status and Ki-67 expression level could be an excellent prognostic marker to predict the post-operative recurrence of stage I ADC.
Lung Cancer 2009 Sep
PMID:Prognostic value of KRAS mutations and Ki-67 expression in stage I lung adenocarcinomas. 1916 66

About 50% of patients presenting with resectable lung cancer develop distant metastases within 5 years. Genomic markers predicting metastatic behaviour of squamous cell lung carcinoma (SCC) are currently underexposed. We analyzed a cohort of patients with primary SCC using array-based comparative genomic hybridization (aCGH) to identify which genomic aberrations are related to metastatic behaviour. The cohort consisted of 34 patients with a follow-up of at least 5 years, 8 with metastases in regional lymph nodes only and 26 patients without any metastases at the time of surgery. Eleven of the latter 26 developed metastases in distant organs within 3 years after surgery. Copy number changes observed in at least 40% of all SCC included gains at chromosomal arms 3q, 5p, 8q, 19q, 20p, 22q and losses at 3p, 4p, 4q, 5q, 8p and 9p. High copy number amplifications were observed at 2p15-p16, 3q24-q29, 8p11-p12, 8q23-q24, and 12p12, containing candidate oncogenes such as BCL11A, REL, ECT2, PIK3CA, ADAM9, MYC and KRAS. Amplification of 2p15-p16 is a novel finding in SCC. Another novel finding is the homozygous deletion observed at 4q33-34.1 in 15% of the SCC cases. Gains at 7q36, 8p12, 10q22, 12p12, loss at 4p14 and the homozygous deletions at 4q occurred significantly more frequent in SCC from patients with lymph node metastases only. SCC from patients with distant metastases showed a significantly higher gain frequency at 8q22-q24 and loss at 8p23 and 13q21, and a significantly lower gain frequency at 2p12 and 2p16 and loss at 11q25 compared with SCC from patients without metastases. Of these, gains at 7q, 8p and 10q were restricted to SCC with lymph node metastasis and gain at 8q was restricted to patients with distant metastasis. Two genomic aberrations, i.e. loss of 4p and gain of 19q12 were observed more frequently in SCC with only lymph node metastases as compared to SCC with distant metastases. In conclusion, we identified genomic aberrations in primary SCC that were related to lymph node or distant metastases.
Lung Cancer 2009 Dec
PMID:Genomic aberrations in squamous cell lung carcinoma related to lymph node or distant metastasis. 1932 46

The present study investigated the potential difference between EGFR-mutated lung adenocarcinoma (ADC) and KRAS-mutated ADC in relation to past illness and family history. Among the 153 tumors examined, 33 (21.6%) were EGFR-mutated, and 22 (14.4%) were KRAS-mutated. The EGFR-mutated cases showed a significantly higher prevalence of past illness involving the gastric cancer in males (EGFR 3/8 (37.5%), KRAS 0/13 (0.0%), no mutation (NONE) 1/57 (1.8%); Fisher's exact test, P=0.0064) or uterine myoma in females (EGFR 8/25 (32.0%), KRAS 0/9 (0.0%), NONE 3/41 (7.3%); Fisher's exact test, P=0.0139). No association between the mutations and family history was found. The EGFR-mutated ADC is therefore likely to develop through a distinct carcinogenetic pathway from the others, but genetic backgrounds seemed unlikely to be determinant predisposing to the EGFR-mutated ADC.
Lung Cancer 2009 Dec
PMID:Significant association between EGFR-mutated lung adenocarcinoma and past illness from gastric cancer or uterine myoma: its implication in carcinogenesis. 1936 47

Recently, the fusion gene EML4-ALK was identified in non-small cell lung carcinoma, which could be a potential therapeutic target. We investigated the prevalence of anaplastic lymphoma kinase protein expression in these tumors by immunohistochemistry and correlated the results with data from ALK molecular studies. Gene expression profiling was performed on 35 adenocarcinomas to identify cases with ALK gene up-regulation, which was correlated with protein overexpression by immunohistochemistry. Immunohistochemistry was also performed on an independent cohort consisting of 150 adenocarcinomas and 150 squamous cell carcinomas to evaluate the utility of anaplastic lymphoma kinase immunostaining as a screening tool. Florescence in situ hybridization for the ALK locus and reverse transcriptase-polymerase chain reaction for EML4-ALK were performed on tumors positive for anaplastic lymphoma kinase by immunohistochemistry. Transcriptional up-regulation of ALK was identified in 2 (6%) of 35 adenocarcinomas by gene expression profiling. These 2 cases were positive for anaplastic lymphoma kinase by immunohistochemistry, whereas the remaining 33 cases were completely negative. In the independent cohort, anaplastic lymphoma kinase immunostaining was positive in 1 of 150 squamous cell carcinomas and in 3 of 150 adenocarcinomas. The 6 cases positive for anaplastic lymphoma kinase by immunohistochemistry showed evidence of ALK locus rearrangement by florescence in situ hybridization but were negative for EGFR and KRAS mutation. The presence of EML4-ALK fusion transcript was confirmed in 2 cases by reverse transcriptase-polymerase chain reaction. In conclusion, anaplastic lymphoma kinase immunoreactivity in non-small cell lung carcinomas was associated with transcriptional up-regulation, ALK locus rearrangement, and the presence of EML4-ALK fusion transcript. Anaplastic lymphoma kinase immunohistochemistry may have utility as a screening tool or as a surrogate marker for the molecular techniques to detect the EML4-ALK fusion gene in these tumors.
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PMID:Anaplastic lymphoma kinase immunoreactivity correlates with ALK gene rearrangement and transcriptional up-regulation in non-small cell lung carcinomas. 2016 22


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