The sensitivity and specificity of immunohistochemistry (IHC) was compared with the standard polymerase chain reaction (PCR)-based method for detecting common activating epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC). Additionally, we evaluated predictive value of IHC EGFR mutation-positive status for EGFR tyrosine kinase inhibitor (TKI) treatment outcome and estimated cost-effectiveness for the upfront IHC testing. The trial included 79 consecutive EGFR mutation-positive and 29 EGFR mutation-negative NSCLC cases diagnosed with reflex PCR-based testing. Two mutation-specific antibodies against the most common exon 19 deletion, namely E746-A750del (clone SP111) and L858R mutation (clone SP125) were tested by using automated immunostainer. A decision tree was used for the cost-effectiveness analysis. The overall sensitivity and specificity of the IHC-based method compared with the PCR-based method were 84.8% (95% confidence interval [CI] 74.6-91.6) and 100% (95% CI 85.4-100), respectively. The median progression-free survival (PFS) and overall survival (OS) of patients with IHC-positive EGFR mutation status were highly comparable to the total cohort (PFS: 14.3 vs. 14.0 months; OS: 34.4 vs. 34.4 months). The PCR and IHC cost ratio needs to be approximately 8-to-1 and 4-to-1 in White and Asian populations, respectively, to economically justify upfront use of IHC. The trial confirmed an excellent specificity with fairly good sensitivity of IHC with mutation-specific antibodies for common EGFR mutations and the accuracy of IHC testing for predicting response to EGFR TKIs. The use of upfront IHC depends mainly on the population EGFR mutation positivity probability.
COBISS.SI-ID: 2609787
The data on expression and clinical impact of cancer stem cell markers SOX2, NANOG and OCT4 in lung cancer is still lacking. The aim of our study was to compare SOX2, NANOG and OCT4 mRNA expression levels in whole blood between advanced small-cell lung cancer (SCLC) patients and healthy controls, and to correlate mRNA expression with progression-free survival (PFS) after first-line chemotherapy and overall survival (OS) in advanced SCLC patients. 50 advanced SCLC patients treated with standard chemotherapy and followed at University Clinic Golnik, Slovenia, between 2009 and 2013 were prospectively included. SOX2, NANOG and OCT4 mRNA expression levels were determined using TaqMan qPCR in whole blood collected prior to chemotherapy. SOX2 mRNA expression was significantly higher in whole blood of SCLC patients compared to healthy controls (p = 0.006). Significant correlation between SOX2 mRNA expression levels and the number of distant metastatic sites was established (p = 0.027). In survival analysis, patients with high SOX2 expression had shorter OS (p = 0.017) and PFS (p = 0.046). In multivariate Cox analysis, an independent value of high SOX2 expression for shorter OS (p = 0.002), but not PFS was confirmed. No significant differences were observed for NANOG or OCT4 expression levels when comparing SCLC patients and healthy controls neither when analysing survival outcomes in SCLC patients. SOX2 mRNA expression in whole blood might be a promising non-invasive marker for molecular screening of SCLC and important prognostic marker in advanced chemotherapy-treated SCLC patients. Further evaluation of SOX2 as a possible screening/prognostic marker and a therapeutic target of SCLC is warranted.
COBISS.SI-ID: 2078843
CtDNA EGFR mutation (EGFRmu) analysis is used to improve detection of resistant mutations and to overcome the limitation of repeated tissue sampling after resistance to EGFR TKI develops. 50–60% of resistance mechanism is due to secondary EGFR T790M mutation. The aim of our analysis was to evaluate the type and frequency of EGFRmu in ctDNA and in tissue at disease progression on non-mutant specific EGFR TKI. Since May 2014 untill this publication 41 EGFRmu positive pts with advanced NSCLC were treated with non-mutant specific EGFR TKI since then and followed. Blood samples for EGFRmu analysis were taken at each scheduled visit. Tissue rebiopy was also performed at disease progression when feasible for the patient. Overall, T790M mutations in ctDNA and/or tissue was detected in 12/21 (57.6%) of all our pts at the time of progression. We confirmed a high rate of ctDNA EGFRmu positivity at the time of progression on EGFR TKI in our group of routinely treated pts. The detection rate of T790M mutation was lower than expected – only 43%.
COBISS.SI-ID: 2616187
With introduction of immunotherapy (IT) into the treatment of advanced non-small-cell lung cancer (NSCLC), a need for predictive biomarker became apparent. Programmed death ligand 1 (PD-L1) protein expression is most widely explored predictive marker for response to IT. We assessed PD-L1 expression in tumor cells (TC) and immune cells (IC) of squamous-cell carcinoma (SCC) and adenocarcinoma (AC) patients. We obtained surgically resected tumor specimens and assessed PD-L1 expression by immunohistochemistry after staining them with antibody SP142 (Ventana, USA). Clinicopathological characteristics were acquired from the hospital registry database. We found thataPD-L1 expression was significantly higher in TC of SCC compared to AC at both cut-off values (52% vs. 17%, p = 0.016 and 52% vs. 14%, p = 0.007, respectively) no difference in PD-L1 expression in IC of SCC and AC was found. Our results suggest a significantly higher PD-L1 expression in TC of SCC compared to AC, regardless of the cut-off value. PD-L1 expression in IC is high in both histological subtypes of NSCLC, and adds significantly to the overall positivity of AC but not SCC, which might have implcations on response to PD-L1 inhibitors in lung cancer.
COBISS.SI-ID: 4381553
The introduction of targeted treatments for subsets of non-small cell lung cancer (NSCLC) has highlighted the importance of accurate molecular diagnosis to determine if an actionable genetic alteration is present. A questionnaire about molecular testing and NSCLC management was distributed to relevant specialists in nine CEE countries. A very high proportion of lung cancer cases are confirmed histologically/cytologically (75–100%), and molecular testing of NSCLC samples has been established in all evaluated CEE countries. Most countries follow national or international guidelines on which patients to test for EGFR mutations and ALK rearrangements. Slovenia has been one of the first CEE countries with established reflex molecular testing of NSCLC. In most centres at that time, testing was undertaken on request of the clinician rather than on the preferred reflex basis. Molecular testing is established throughout the CEE region, but improved and unbiased reimbursement remains a major challenge for the future.
COBISS.SI-ID: 2048273521