Search

Background/aim: KRAS is one of the frequently mutated genes in human cancers and often relates with drug resistance and poor prognosis. PANAMutyper™ is a novel technology that integrates PNAClamp™ and PANA S-Melting™. In the present study, PANAMutyper™ and PNAClamp™ were compared for the detection of KRAS mutations using different samples of patients with malignant pleural effusion., Patients and Methods: A total of 103 patients (including 56 lung adenocarcinoma, 10 lung squamous carcinoma, 17 small cell lung cancer, 3 large cell lung cancer, 3 stomach cancer, 2 ovarian cancer, and others) with malignant pleural effusion were investigated using matched tumor tissue, cell block, and pleural effusion samples. The diagnostic performance of these two methods was compared., Results: KRAS mutations were detected in 18 (17.5%) of 103 patients using tissue, cell block, and pleural effusion samples. All 18 patients with KRAS mutations were detected by PANAMutyper™ using any sample type, however, only 7 cases were detected by PNAClamp™. Among the subtypes of KRAS mutations, substitution in codon 12, 35G>T was the most frequent, followed by substitution in codon 12, 35G>A and codon 12, 34G>A. In pleural effusion specimens, PANAMutyper™ showed a better diagnostic performance compared to PNAClamp™., Conclusion: PANAMutyper™ had a diagnostic superiority for the detection of KRAS mutations in patients with malignant pleural effusion compared to PNAClamp™, although there was a concordance between PANAMutyper™ and PNAClamp™ results. Therefore, PANAMutyper™ can be used for a more sensitive and accurate detection of KRAS mutations., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

A higher platelet-to-lymphocyte ratio (PLR) has a clinical correlation with shorter survival in non-small cell lung cancer (NSCLC). The present study evaluated the association between the PLR and survival in patients with advanced NSCLC with malignant pleural effusion (MPE). Between January 2012 and July 2016, 237 patients with stage IV NSCLC were selected for evaluation. Receiver operating characteristic analysis was used to determine a cutoff for the PLR. Clinicopathological characteristics were compared between the high and low PLR groups, and the role of PLR as a predictive/prognostic maker was investigated. Among the 237 patients, 122 were assigned to the low PLR group and the other 115 to the high PLR group. According to multivariate analysis, male sex, not receiving active anticancer treatment, low hemoglobin level, low albumin level, high C-reactive protein level, and high PLR were identified as significant risk factors for shorter overall survival (OS) (p = 0.010, <0.001, 0.011, 0.004, 0.003, and <0.001, respectively). In the subgroup multivariate analysis of driver mutation-negative NSCLC, high Eastern Cooperative Oncology Group score, not receiving active anticancer treatment, low hemoglobin level, high C-reactive protein level, and high PLR were identified as significant risk factors for shorter OS (p = 0.047, <0.001, = 0.036, = 0.003, and <0.001, respectively). A high pretreatment PLR is independently associated with poor survival in stage IV NSCLC with MPE and in a subgroup of epidermal growth factor receptor and anaplastic lymphoma kinase wild-type NSCLC.

Background/aim: This study compared the efficacy of PANAMutyper™, a novel technology that integrates PNAClamp™ and PANA S-Melting™, and PNAClamp™ alone for the detection of EGFR mutations in lung cancer patients., Materials and Methods: PANAMutyper™ and PNAClamp™ were used to assess the EGFR mutation status in tissue, cell block, pleural effusion, and blood samples of 90 lung cancer patients with malignant pleural effusion., Results: PANAMutyper™ detected more EGFR mutations than PNAClamp™, especially in body fluids (pleural effusion and serum). Patients with additional EGFR mutations detected using PANAMutyper™ had a favorable response to EGFR-tyrosine kinase inhibitor (TKI) treatment., Conclusion: The diagnostic performance of PANAMutyper™ was superior to that of PNAClamp™ for the detection of EGFR mutations. It was also better at identifying lung cancer patients with malignant pleural effusion who were likely to benefit from EGFR-TKI treatment., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: A combination of platelet and lymphocyte to monocyte ratio (LMR) (abbreviated as COP-LMR) has been recently evaluated as systemic inflammatory marker for prognostication in lung cancer. While previous study on COP-LMR has evaluated its prognostic value in NSCLC patients who underwent curative resections, the combination of these two markers has not been evaluated in advanced NSCLC yet., Objectives: In this study, we evaluated the prognostic value of COP-LMR in stage IV NSCLC with malignant pleural effusion under active anticancer treatment., Methods: Between January 2012 and July 2016, 217 patients with stage IV NSCLC and MPE undergoing active anticancer treatment were selected for evaluation. If patients had both low LMR (< 2.47) and increased platelet (> 30.0 ×10(4) mm-3), they were assigned to COP-LMR group 2. Patients with one parameter were assigned to COP-LMR group 1. If none, patients were assigned to COP-LMR group 0., Results: Median overall survival (OS) (P < 0.001), progression free survival (PFS) (P < 0.001) and histological feature (P = 0.003) showed significant differences among COP-LMR groups. For COP-LMR groups 0, 1 and 2, median survival times were 35.9, 14.7 and 7.4 months, respectively, while median progression free times were 19.2, 13.3 and 7.4 months, respectively. Older age, male, low albumin, high CRP and high COP-LMR (0 vs 1, P = 0.021, hazard ratio (HR): 1.822, 95% confidence interval (CI): 1.096-3.027 and 0 vs 2, P = 0.003, HR: 2.464, 95% CI: 1.373-4.421) were independent predictive factors for shorter OS. Age, sex, histology, albumin, or CRP had no significant influence on PFS. High COP-LMR was the significant factor in predicting shorter PFS (0 vs 1, P = 0.116 and 0 vs 2, P = 0.007, HR: 1.902, 95% CI: 1.194-3.028)., Conclusions: A combination of pretreatment LMR and platelet levels can be used to predict short survival in stage IV NSCLC patients who underwent active anticancer treatment., Competing Interests: The authors have declared that no competing interests exist.

Background and Objective: Peptide nucleic acid (PNA)-mediated real-time polymerase chain reaction clamping was recently developed to improve mutation detection sensitivity. Pleural effusion could be a good sample candidate for mutation analysis. To establish if PNA clamping could be used to detect KRAS mutation in particular in pleural effusion, we analysed its diagnostic performance., Methods: We studied 57 patients with malignant effusion. KRAS mutation was evaluated in samples of matched tumour tissue, cell block, pleural effusion and serum using PNA clamping and direct sequencing., Results: The detection rate of KRAS mutation using pleural effusion was 14% for PNA clamping and 10.5% for direct sequencing. The κ coefficient between the two methods was 0.76 (P value < 0.0001), 1.00 (P value < 0.0001) and 0.87 (P value < 0.0001) in pleural effusion, tissue and cell block, respectively. The diagnostic performance of KRAS mutation detection from pleural effusion compared with the results obtained for all samples combined showed that the sensitivity, specificity, positive predictive value and negative predictive value were as follows: 89, 100, 100 and 98%, respectively for PNA clamping; 67, 100, 100 and 94%, respectively for directing sequencing., Conclusions: The current study suggests that PNA clamping had a good concordance with direct sequencing for the detection of KRAS mutation in patients with malignant effusion. Furthermore, the good diagnostic performance obtained from pleural effusion samples provides evidence that pleural effusion can be a useful source for detecting KRAS mutation in a clinical setting, in which the collection of tumour tissues is challenging., (© 2014 Asian Pacific Society of Respirology.)

Peptide nucleic acid (PNA)-mediated real-time PCR clamping has higher sensitivity than conventional direct sequencing for detecting mutations. Pleural effusion and serum may provide good samples in which to detect epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) patients. We studied 37 NSCLC patients with malignant pleural effusion. EGFR mutations were assessed by PNA clamping and direct sequencing using tumor tissues, cell blocks, pleural effusion, and serum. Concordance between PNA clamping and direct sequencing results, and the diagnostic performance of pleural effusion were investigated. The κ coefficients for the two methods were 0.68 (p = 0.0007), 0.91 (p < 0.0001), 0.75 (p < 0.0001) and -0.01 (p = 0.8639) for tissues, cell blocks, pleural effusion, and serum, respectively. The diagnostic performance of pleural effusion compared with the combination of tumor tissue and cell blocks showed 89% sensitivity, 100% specificity, positive predictive value of 100%, and negative predictive value of 95% by PNA clamping, and 67% sensitivity, 90% specificity, positive predictive value of 75%, and negative predictive value of 86% by directing sequencing. A patient in whom an EGFR mutation was identified in pleural effusion only by PNA clamping showed a significant response to EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment. In contrast to the limited role of serum samples, pleural effusion had a diagnostic performance for the detection of EGFR mutations in NSCLC that was comparable to that of tumor tissues and cell blocks. The diagnostic performance of PNA clamping was good compared with that of direct sequencing. A more sensitive and accurate detection of EGFR mutations would benefit patients by allowing a better prediction of the response to EGFR-TKI treatment., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)