0000000000239961

AUTHOR

Alex Soltermann

Prevalence and Clinical Outcomes for Patients With ALK Gene Rearrangement in Europe: Preliminary Results from the European Thoracic Oncology Platform Lungscape Project

ABSTRACT Background The prevalence of ALK gene rearrangement (ALK+) in European patients with non-small cell lung cancer (NSCLC) is unknown. The Lungscape project provides a platform to evaluate its expression and clinical significance in a large cohort of patients with resected NSCLC from 13 European sites in 11 countries. Methods Participating sites retrospectively identified cases of NSCLC with clinical demographic and outcome data, and available tissue for research according to predefined protocol criteria. Local ethical and regulatory approvals were adhered to. Clinical data were entered to a central, secure database. Accepted cases on the basis of completeness of clinical data were as…

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Prevalence and Clinical Outcomes for Patients With ALK-Positive Resected Stage I to III Adenocarcinoma: Results From the European Thoracic Oncology Platform Lungscape Project

Purpose The prevalence of anaplastic lymphoma kinase (ALK) gene fusion (ALK positivity) in early-stage non–small-cell lung cancer (NSCLC) varies by population examined and detection method used. The Lungscape ALK project was designed to address the prevalence and prognostic impact of ALK positivity in resected lung adenocarcinoma in a primarily European population. Methods Analysis of ALK status was performed by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) in tissue sections of 1,281 patients with adenocarcinoma in the European Thoracic Oncology Platform Lungscape iBiobank. Positive patients were matched with negative patients in a 1:2 ratio, both for IHC and for …

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Germinal Centers Determine the Prognostic Relevance of Tertiary Lymphoid Structures and Are Impaired by Corticosteroids in Lung Squamous Cell Carcinoma.

Abstract In solid tumors, the presence of lymph node–like structures called tertiary lymphoid structures (TLS) is associated with improved patient survival. However, little is known about how TLS develop in cancer, how their function affects survival, and whether they are affected by cancer therapy. In this study, we used multispectral microscopy, quantitative pathology, and gene expression profiling to analyze TLS formation in human lung squamous cell carcinoma (LSCC) and in an experimental model of lung TLS induction. We identified a niche of CXCL13+ perivascular and CXCL12+LTB+ and PD-L1+ epithelial cells supporting TLS formation. We also characterized sequential stages of TLS maturation…

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The inhibitor of differentiation-1 (Id1) enables lung cancer liver colonization through activation of an EMT program in tumor cells and establishment of the pre-metastatic niche

Abstract: Id1 promotes carcinogenesis and metastasis, and predicts prognosis of non-small cell lung cancer (NSCLC)-adenocarcionoma patients. We hypothesized that Id1 may play a critical role in lung cancer colonization of the liver by affecting both tumor cells and the microenvironment. Depleted levels of Id1 in LLC (Lewis lung carcinoma cells, LLC shId1) significantly reduced cell proliferation and migration in vitro. Genetic loss of Id1 in the host tissue (Id1(-/-) mice) impaired liver colonization and increased survival of Id1 animals. Histologically, the presence of Idl in tumor cells of liver metastasis was responsible for liver colonization. Microarray analysis comparing liver tumor n…

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