1525P - Prevalence and clinical associations of PTEN loss in non-small cell lung carcinoma (NSCLC) patients (pts) of the European Thoracic Oncology Platfor...

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Alex Soltermann
Citation Annals of Oncology (2016) 27 (6): 526-544. 10.1093/annonc/mdw392
Authors A. Soltermann1, U. Rulle1, O. Dafni2, E. Verbeken3, E. Thunnissen4, A. Warth5, R. Cheney6, A. Sejda7, E. Speel8, L. Bille Madsen9, D. Nonaka10, A. Navarro11, I. Sansano12, A. Marchetti13, S. Finn14, R. Kammler15, K. Schulze16, L. Bubendorf17, R.A. Stahel18, O.B.O. Lungscape19
  • 1Pathology, Universitätsspital Zürich, 8091 - Zürich/CH
  • 2Biostatistics, Frontier Science Foundation – Hellas, 15773 - Athens/GR
  • 3Pathology, University Hospitals Leuven - Campus Gasthuisberg, Leuven/BE
  • 4Pathology, Vrije University Medical Centre (VUMC), 1081 HV - Amsterdam/NL
  • 5Pathology, University Hospital Heidelberg, Heidelberg/DE
  • 6Pathology And Laboratory Medicine, Roswell Park Cancer Institute, Buffalo/US
  • 7Pathology, Medical University of Gdansk, Gdansk/PL
  • 8Pathology, Maastricht University Medical Center (MUMC), Maastricht/NL
  • 9Pathology, Aarhus University Hospital, Aarhus C/DK
  • 10Pathology, The Christie NHS Foundation Trust, Manchester/GB
  • 11Pathology, Hospital General Universitario Valencia, Valencia/ES
  • 12Pathology, Vall d`Hebron University Hospital Institut d'Oncologia, Barcelona/ES
  • 13Pathology, Ospedale Clinicizzato, Chieti/IT
  • 14Cancer Molecular Diagnostics, St James's Hospital, Dublin/IE
  • 15Translational Research Coordination, European Thoracic Oncolocy Platform, 3008 - Bern/CH
  • 16Oncology Biomarker Development, Genentech, 94080 - San Francisco/US
  • 17Institute For Pathology, Universitätsspital Basel, 4031 - Basel/CH
  • 18Clinik And Policlinic Of Oncology, Universitätsspital Zürich, 8091 - Zürich/CH
  • 19K. Monkhorst, The Netherlands Cancer Institute Amsterdam; K.m. Kerr, Royal Infirmary Aberdeen; S. Peters, European Thoracic Oncolocy Platform, 3008 - Bern/CH

Abstract

Background

Loss of PTEN might be a prognostic biomarker in NSCLC.

Methods

We explored the prevalence of PTEN loss and its association with clinico-pathologic parameters as well as patient outcome (overall survival (OS), relapse-free survival (RFS) and time to relapse (TTR)) in the ETOP Lungscape cohort of resected stages I–III NSCLC. Tumor tissue was assessed for PTEN protein expression using immunohistochemistry on tissue microarrays. All cases were locally H-scored by ETOP pathologists, after having passed a stringent External Quality Assessment, and were centrally analyzed with pixel-based Image-J computer analysis. PTEN loss was defined as H-score = 0.

Results

PTEN expression in tumor tissue was evaluable in 2245 pts from 16 ETOP Lungscape centers with the following characteristics: median follow-up 4.8 years; 54.3% of pts still alive; median age 66.4 years; 65.9% male; 10.6%, 53.9% and 31.5% never, former and current smokers, respectively, and 4.1% with unknown smoking status. Stage distribution was: IA 22.4%, IB 25.9%, IIA 16.8%, IIB 12.2%, IIIA 20.8%, IIIB 1.9%. Histology was 48.7 % adenocarcinoma (AC), 43.8% squamous cell carcinoma (SCC), 4.4% large cell, 3.2% other types. PTEN loss was detected in 981 pts (43.7%; 95% confidence interval (CI): 41.6%-45.8%) and was significantly associated with male sex (47.2% in men versus 36.9% in women; p 

Conclusions

In this large cohort of resected NSCLC, PTEN loss was present in half of the SCC and in one third of AC, and associated with poorer pts' prognosis in the latter. Computerized immunoreactivity measurements are a promising alternative to pathologists' scorings.

Clinical trial identification

ETOP Lungscape 002 PTEN

Legal entity responsible for the study

European Thoracic Oncology Platform (ETOP)

Funding

Genentech Inc.

Disclosure

K. Schulze: Employee of Genentech Inc. 1 DNA Way, South San Francisco, CA 94080. All other authors have declared no conflicts of interest.