Lung neuro-endocrine tumors: Correlation of ubiquitinylation and | 5292
Translational Medicine

Translational Medicine
Open Access

ISSN: 2161-1025

+44 1223 790975

Lung neuro-endocrine tumors: Correlation of ubiquitinylation and sumoylation with nucleocytosolic partitioning of PTEN

4th International Conference on Translational Medicine

October 26-28, 2015 Baltimore, USA

Alex Soltermann1, Stephane Collaud1, Verena Tischler1, Andrej Atanassoff1, Thomas Wiedl1, Paul Komminoth2, Christian Oehlschlegel3 and Walter Weder1

1University Hospital of Zurich, Switzerland 2Triemli Hospital, Switzerland 3Cantonal Hospital, Switzerland

Scientific Tracks Abstracts: Transl Med

Abstract :

Background: The tumor suppressor phosphatase and tensin homolog (PTEN) is a pleiotropic enzyme, inhibiting phosphatidylinositol- 3 kinase (PI3K) signaling in the cytosol and stabilizing the genome in the nucleus. Nucleo-cytosolic partitioning is dependent on the post-translational modifications ubiquitinylation and sumoylation. This cellular compartmentalization of PTEN was investigated in lung neuro-endocrine tumors (lung NET). Methods: Tumor tissues from 192 lung NET patients (surgical specimens=183, autopsies=9) were investigated on tissue microarrays. PTEN was H-scored by two investigators in nucleus and cytosol using the monoclonal antibody 6H2.1. Results were correlated with immunoreactivity for USP7 (herpes virus-associated ubiquitin-specific protease 7) and SUMO2/3 (small ubiquitin-related modifier protein 2/3) as well as PTEN and p53FISH gene status. Clinico-pathologic data including overall survival, proliferation rate and diagnostic markers (synaptophysin, chromogranin A, Mib-1, TTF-1) were recorded. Results: The multicentre cohort included 58 typical carcinoids (TC), 42 atypical carcinoids (AC), 32 large cell neuro-endocrine carcinomas (LCNEC) and 60 small cell lung carcinomas (SCLC). Carcinoids were smaller in size and had higher synaptophysin and chromogranin-A, but lower TTF-1 expressions. Patients with carcinoids were predominantly female and 10 years younger than patients with LCNEC/SCLC. In comparison to the carcinoids, LCNEC/SCLC tumors presented a stronger loss of nuclear and cytosolic PTEN associated with a loss of PTEN and p53. Concomitantly, a loss of nuclear USP7 but increase of nuclear and cytosolic SUMO2/3 was found. Loss of nuclear and cytosolic PTEN, loss of nuclear USP7 and increase of cytosolic SUMO2/3 thus correlated with poor survival. Among carcinoids, loss of cytosolic PTEN was predominantly found in TTF1-negative larger tumors of male patients. Among SCLC, loss of both cytosolic and nuclear PTEN but not proliferation rate or tumor size delineated a subgroup with poorer survival (all p-values <0.05). Conclusions: Cellular ubiquitinylation and sumoylation likely influence the functional PTEN loss in high grade lung NET. Both nuclear and cytosolic PTEN immunoreactivity should be considered for correlation with clinico-pathologic parameters.

Biography :

Alex Soltermann is an Assistant Professor of the University of Zurich and consultant Surgical Pathologist at the Institute of Surgical Pathology, University Hospital Zurich, Switzerland, where he is responsible for lung and head neck pathology. He is also the head of In-situ IHC/FISH laboratory. His research is focused on the tumor-stroma interactions of lung squamous cell carcinoma and corresponding localized molecular analysis of tumor tissue using laser capture micro-dissection and micro-fluidic probes. Currently, he is working on a 3D tumor model using a combination of serial histologic sections and parallel X-ray micro-tomography. He has 72 original publications.