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Mesenchymal-to-epithelial transition (MET) exon 14 skipping mutations and MET gene amplification occur in 3-5% of non-small cell lung cancer (NSCLC) patients. Tyrosine kinase inhibitors (TKIs) targeting MET alterations have shown promising results in these patients.The aim of this study was to describe the genomic profile, PD-L1 expression and clinicopathological features of MET dysregulated NSCLC.We identified 188 patients with advanced-stage NSCLC with data on MET expression by immunohistochemistry (IHC). IHC for PD-L1 expression was performed in 131 patient samples, and next-generation sequencing (NGS) analysis was performed in 109 patient samples.MET exon 14 skipping alterations were identified in 16 (14.7%) samples, MET amplifications with cut-off ≥4 copy number variations were identified in 11 (10.1%) samples, and an oncogenic MET mutation (MET p.D1228N) was identified in 1 (0.9%) sample. 12/15 tumors (80.0%) harboring MET exon 14 alterations and 7/11 (63.6%) MET-amplified tumors expressed PD-L1 in ≥1% of tumor cells. Tumors harboring MET exon 14 skipping alterations expressed PD-L1 more frequently than MET wild-type IHC-positive tumors (p = 0.045). Twenty-five percent of MET exon 14-altered cases and 33% of MET-amplified cases harbored potentially targetable oncogenic co-mutations in KRAS, BRAF, and EGFR. The most frequent co-occurring mutations in all MET-altered tumors were TP53, KRAS, BRAF, and CDK4.We demonstrated that MET exon 14 skipping alterations and MET amplification are not mutually exclusive to other oncogenic co-mutations, and report the association of genomic MET alterations with PD-L1 expression. Since genomic MET alterations are emerging targets requiring upfront treatment, optimal understanding of the co-mutational landscape for this patient population is needed.

Soluble αKlotho (sKl) is a disease-specific biomarker that is elevated in patients with acromegaly and declines after surgery for pituitary adenoma. Approximately 25% of patients do not achieve remission after surgery, therefore a risk stratification for patients early in the course of their disease may allow for the identification of patients requiring adjuvant treatment. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) have been assessed as biomarker for disease activity, however the value of sKl as a predictive biomarker of surgical success has not been evaluated yet. In this study, we measured serum biomarkers before and after transsphenoidal pituitary surgery in 55 treatment-naïve patients. Based on biochemical findings at follow-up (7–16 years), we divided patients into three groups: (A) long-term cure (defined by normal IGF-1 and random low GH (

BACKGROUND A population-based analysis of patients with glioma diagnosed between 1980 and 1994 in the Canton of Zurich in Switzerland confirmed the overall poor prognosis of glioblastoma. To explore changes in outcome, registry data were reevaluated for patients diagnosed between 2005 and 2009. METHODS Patients with glioblastoma who were diagnosed between 2005 and 2009 were identified by the Zurich and Zug Cancer Registry. The prognostic significance of epidemiological and clinical data, isocitrate dehydrogenase 1 (IDH1)(R132H) mutation status, and O6 methylguanine DNA methyltransferase (MGMT) promoter methylation status was analyzed using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS A total of 264 patients with glioblastoma were identified, for an annual incidence of 3.9 compared with the previous incidence of 3.7. The mean age of the patients at the time of diagnosis was 59.5 years in the current cohort compared with 61.3 years previously. The overall survival (OS) rate was 46.4% at 1 year, 22.5% at 2 years, and 14.4% at 3 years in the current study compared with 17.7% at 1 year, 3.3% at 2 years, and 1.2% at 3 years as reported previously. The median OS for all patients with glioblastoma was 11.5 months compared with 4.9 months in the former patient population. The median OS was 1.9 months for best supportive care, 6.2 months for radiotherapy alone, 6.7 months for temozolomide alone, and 17.0 months for radiotherapy plus temozolomide. Multivariate analysis revealed age, Karnofsky performance score, extent of tumor resection, first-line treatment, year of diagnosis, and MGMT promoter methylation status were associated with survival in patients with IDH1(R132H) -nonmutant glioblastoma. CONCLUSIONS The OS of patients newly diagnosed with glioblastoma in the Canton of Zurich in Switzerland markedly improved from 1980 through 1994 to 2005 through 2009. Cancer 2016;122:2206-15. © 2016 American Cancer Society.

Objective: Klotho is a lifespan-influencing gene expressed in the kidneys and other tissues, including the pituitary gland. Soluble alpha-Klotho (alpha-KL) is released into the circulation. The aim of this prospective controlled study is to present baseline serum levels of alpha-KL in patients with [for full text, please go to the a.m. URL], 64. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)