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pathophysiological mechanisms related to carcinogenesis. Lung cancer is an important health problem and new biomarkers are needed for better patients' stratification. This study was conducted to elucidate the clinical significance of cannabinoid receptor CB2 expression in NSCLC. Method: Cannabinoid receptor CB2 expression was evaluated immunohistochemically on Tissue MicroArrays (TMAs) of 79 tissue samples from NSCLC patients and it was correlated to clinicopathological parameters and overall survival (OS). Result: 79 NSCLC patients (48 adenocarcnomas and 31 squamous carcinomas) were studied. Enhanced cannabinoid receptor CB2 expression was observed in 20/79 (25.3 % ) NSCLC patients. In particular, enhanced cannabinoid receptor CB2 expression was found in 9 out of 48 (18.8%) adenocarcinomas and in 11 out of 31 (35.5%) of squamous cell carcinomas. Cannabinoid receptor CB2 expression was significantly associated with sex, smoking history and histological type (p¼0.019, p¼0.022 and p¼0.032, respectively). In adenocarcinomas, cannabinoid receptor CB2 expression was correlated with overall survival (log-rank test, p¼0.031), while there was a trend for correlation with tumor size (p¼0.091) and lymph node metastasis (p¼0.074). However, in squamous carcinomas cannabinoid receptor CB2 expression was not found to be significantly correlated with any of clinicopathological parameters or survival. Conclusion: Cannabinoid receptor CB2 receptor may be involved in NSCLC malignant tranformation and growth particularly in adenocarcinomas. Therefore, cannabinoid receptor CB2 receptor could be considered as a potential biomarker or a therapeutic target in NSCLC. More studies needed to elucidate the role of this molecule in NSCLC.Background: Tumor spread through air spaces (STAS) has been reported as a form of tumor invasion having an unfavorable prognosis mainly in small lung adenocarcinomas, but the significance of STAS in lung squamous cell carcinomas is not well known. The aim of this study was to analysis STAS in stage I lung squamous cell carcinomas. Method: 39 completely surgically resected (lobectomy) stage I lung squamous cell carcinomas from 2005 to 2009 were included in this study. We examined all tumor edges to find floating tumor cells or clusters, STAS. A statistical analysis was performed to determine the impact of clinicopathologic parameters on STAS and to clarify the relationship between STAS and patient survival. Result: STAS was present in 18 of 39 cases (46.2%). There were no statistically significant associations between STAS and any clinicopathologic parameters including stage and lymph-vascular invasions. There was a significant association between presence of STAS and shorter recurrence-free survival (RFS) in univariate analysis (104.7 months with STAS, 145.5 months without STAS). In a multivariate Cox proportional hazards model, STAS (p¼0.06) couldn't reach a significant predictor of RFS. Conclusion: We found STAS about in half of resected stage I lung squamous cell carcinomas. Presence of STAS was predicti...

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Background: For late stage lung cancer (LC) patients few treatment options are at hand and the survival time is very limited, hence novel therapies and associated biomarkers are urgently needed. Erythropoietin-Producing Hepatocellular carcinoma receptor (Eph) tyrosine kinase family and their ligands, Ephrins, drive multiple hallmarks of cancer e.g. proliferation/invasion. The Eph signaling pathways are attractive drug targets due to their dual role in oncogenesis and tumor progression. We analyzed Ephs/Ephrins signaling in LC cells from pleural effusions (PE) to reveal altered kinase pathways and putative BMs. We also assessed cytotoxicity and kinome alterations in PE tumor cells exposed to targeted agents and chemotherapy in vitro. Methods: Tumor cells purified from PE, assessed for histology, mutation and translocation status (EGFR, KRAS, BRAF and Alk), were grown in vitro. Toxicity of tyrosine kinase inhibitors (TKIs (e.g. erlotinib, crizotinib, AG1024, AZD9291, dasatinib), EGFR blocker (cetuximab) and/or chemotherapy (e.g. cisplatin, gemcitabine, etoposide) were analyzed after 72 h with the Tox8 assay. Ephs/Ephrins signaling components were studied using western blot, immunoprecipitation and by proximity ligation assay. Mutations and signaling heterogeneity were visualized using padlock probe method. For kinome profiling PathScan RTK signalling antibody array was used.