Lee Y.,Center for Lung Cancer |
Shim H.S.,Yonsei University |
Park M.S.,Yonsei University |
Kim J.-H.,Yonsei University |
And 4 more authors.
Clinical Cancer Research | Year: 2012
Purpose: This study aimed to search for predictors of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) efficacy in previously treated patients with advanced squamous cell lung carcinoma in which EGFR mutations are very rare. Experimental Design: EGFR gene copy numbers were assessed by FISH and evaluated as predictors of EGFR-TKI efficacy in 71 patients with advanced squamous cell lung cancerwhoreceived gefitinib or erlotinib as a second-line or higher therapy. The tumors were classified into EGFR/FISH-positive (high polysomy/ gene amplification) and EGFR/FISH-negative (other) groups. Results: EGFR/FISH was positive in 19 (26.7%) patients. Only EGFR/FISH positive status was correlated with the EGFR-TKIs response (EGFR/FISH + vs. EGFR/FISH -, 26.3% vs. 2.0%; P = 0.005). In a multivariate analysis, the risk of progression was lower in EGFR/FISH-positive patients (HR of EGFR/FISH + vs. EGFR/ FISH -, 0.57; P = 0.057) or patients experiencing grade 2 or more rash (HR for rash grade 2 or more vs. less than 2, 0.54; P = 0.042), compared with EGFR/FISH-negative patients or those experiencing grade of less than 2 rash, respectively. When the combined criteria of EGFR/FISH and skin rash severity were analyzed, EGFR/FISH-negative patients with grade less than 2 rash had poorer clinical outcomes than patients with positive EGFR/FISH or grade 2 or more rash, apparent as a lower response rate (0.0% vs. 21.4%; P = 0.003) and a shorter median progression-free survival (1.13 months vs. 3.90 months; P = 0.0002). Conclusions: EGFR/FISH and skin rash severity may be used to identify which patients are likely to gain a benefit from EGFR-TKIs in this population. ©2012 AACR. Source
Kim Y.R.,Catholic University of Korea |
Oh J.E.,Catholic University of Korea |
Kim M.S.,Catholic University of Korea |
Kang M.R.,Catholic University of Korea |
And 4 more authors.
Journal of Pathology | Year: 2010
Nuclear factor erythroid-related factor 2 (NRF2) encodes a transcription factor that induces expression of cytoprotective proteins upon oxidative stress and oncogenic NRF2 mutations have been found in lung and head/neck cancers that inactivate KEAP1-mediated degradation of NRF2. The aim of this study was to catalogue NRF2 mutations in other human cancers. For this, we analysed 1145 cancer tissues from carcinomas from oesophagus, skin, uterine cervix, lung, larynx, breast, colon, stomach, liver, prostate, urinary bladder, ovary, uterine cervix, and kidney, and meningiomas, multiple myelomas, and acute leukaemias by single-strand conformation polymorphism (SSCP) assay. We detected NRF2 mutations in oesophagus (8/70; 11.4%), skin (1/17; 6.3%), lung (10/125; 8.0%), and larynx (3/23; 13.0%) cancers. Of note, all of the 22 mutations except one were found in squamous cell carcinomas (SCCs) (95.5%). The mutations were observed within or near DLG and ETGE motifs that are important in NRF2 and KEAP1 interaction. All of the oesophageal SCCs and skin SCCs with the NRF2 mutations showed increased NRF2 expression in the nuclei. However, none of the SCCs from oesophagus and skin harboured KEAP1 mutation. Our study demonstrated here that NRF2 mutation occurs not only in lung and head/neck cancers, but also in oesophageal and skin cancers. Our data suggest that the NRF2 mutation plays a role in the development of SCC and is a feature of SCC. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Source
Kang H.J.,Center for Lung Cancer |
Hwangbo B.,Center for Lung Cancer
Tuberculosis and Respiratory Diseases | Year: 2013
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is becoming a standard method for invasive mediastinal staging and for the diagnosis of paratracheal and peribronchial lesions. It is essential to understand the technical aspects of EBUS-TBNA to ensure safe and efficient procedures. In this review, we discuss the practical aspects to be considered during EBUS-TBNA, including anesthesia, manipulation of equipment, understanding mediastinal ultrasound images, target selection, number of aspirations needed per target, sample handling, and complications. Copyright ©2013 The Korean Academy of Tuberculosis and Respiratory Diseases. All rights reserved. Source
Hwangbo B.,Center for Lung Cancer |
Lee G.-K.,Center for Lung Cancer |
Lee H.S.,Center for Lung Cancer |
Lim K.-Y.,Center for Lung Cancer |
And 6 more authors.
Chest | Year: 2010
Objective: We performed this study to evaluate the role of transesophageal endoscopic ultrasound with bronchoscope-guided fine-needle aspiration (EUS-B-FNA) following endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the mediastinal staging of lung cancer. Methods: In this prospective study, we applied transbronchial and transesophageal ultrasonography using an ultrasound bronchoscope on patients with confirmed or strongly suspected potentially operable non-small cell lung cancer. Following EBUS-TBNA, EUS-B-FNA was used for mediastinal nodes that were inaccessible or difficult to access by EBUS-TBNA. The accessibility by EBUS-TBNA and EUS-B-FNA to mediastinal nodal stations having at least one node ≥5 mm was also checked. Results: In 150 patients, we performed EBUS-TBNA and EUS-B-FNA on 299 and 64 mediastinal nodal stations, respectively. Among 143 evaluable patients, EBUS-TBNA diagnosed mediastinal metastasis in 38 patients. EUS-B-FNA identified mediastinal metastasis in three additional patients. Surgery diagnosed mediastinal metastasis in four more patients. The sensitivity, negative predictive value, and diagnostic accuracy of EBUS-TBNA in the detection of mediastinal metastasis were 84.4%, 93.3%, and 95.1%, respectively. These values for the combined approach of EBUS-TBNA and EUS-B-FNA increased to 91.1%, 96.1%, and 97.2%, respectively, although the differences were not statistically significant (P = .332, P = .379, and P = .360, respectively). Among 473 mediastinal nodal stations having at least one node ≥5 mm that were evaluated, the proportion of accessible mediastinal nodal stations by EBUS-TBNA was 78.6%, and the proportion increased to 84.8% by combining EUS-B-FNA with EBUS-TBNA (P = .015). Conclusion: Following EBUS-TBNA in the mediastinal staging of potentially operable lung cancer, the accessibility to mediastinal nodal stations increased by adding EUS-B-FNA and an additional diagnostic gain might be obtained by EUS-B-FNA. Trial Registration:clinicaltrials.gov, NCT00741247. © 2010 American College of Chest Physicians. Source
Lee Y.,Center for Lung Cancer |
Lee Y.,Research Institute and Hospital |
Yoon K.-A.,Research Institute and Hospital |
Joo J.,Biometric Research Branch |
And 6 more authors.
Carcinogenesis | Year: 2013
The prognostic significance of inherited genetic variants in advanced-stage non-small cell lung cancer (NSCLC) patients remains unknown. In this study, we genotyped 271 817 singlenucleotide polymorphisms in 348 advanced NSCLC patients who received chemotherapy and analyzed their association with prognosis by using Cox proportional hazard regression model adjusted for known prognostic factors. Top candidate singlenucleotide polymorphisms (SNPs) were selected using the bootstrap re-sampling procedure. Median age of patient population was 56 years. Proportions of female, never smokers and adenocarcinoma were 64.9, 67.5 and 80.4%, respectively. We identified 17 top candidate SNPs related to prognosis using cut-off minimum P value of<5.0× 10-5 in at least 70% of 1000 bootstrap samples. These SNPs were located in the genomic regions of the FAM154A, ANKS1A, DLST, THSD7B, NCOA2, CDH8, SLC35D2, NALCN and EGF genes. The most significant SNP, rs1571228 (9p22.1:FAM154A), was significantly associated with overall survival in dominant model [AG+GG to AA, hazard ratio (HR) of death (95% CI)= 0.53 (0.42-0.67); P= 2.025× 10-7]. The SNP at 4q25:EGF, rs11098063, for which some genetic variations was previously reported to be associated with prognosis, also showed significant association with overall survival in additive model [CC versus CT versus TT, HR (95% CI)= 1.00 versus 0.61 (0.47-0.78) versus 0.39 (0.19-0.79); P= 9.582× 10-6]. Survival differences according to the genotype of these SNPs were independent of sex, smoking, histology and chemotherapy regimens. These results suggested the variants at multiple genetic loci might contribute to the risk of death in advanced NSCLC patients receiving chemotherapy. © The Author 2012. Published by Oxford University Press. All rights reserved. Source