194P - Prevalence and prognostic significance of sodium-dependent phosphate transporter 2b (NaPi2b) protein expression in non-small cell lung cancer (NSCLC)

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Lung and other Thoracic Tumours
Translational Research
Presenter Manolo D'Arcangelo
Citation Annals of Oncology (2014) 25 (suppl_4): iv58-iv84. 10.1093/annonc/mdu326
Authors M. D'Arcangelo1, O.T. Brustugun2, Y. Xiao3, Y. Choi4, C. Behrens5, L.M. Solis5, Y. Wang6, R. Firestein7, T.A. Boyle1, M. Lund-Iversen8, C.J. Rivard1, Å. Helland9, I. Wistuba5, F.R. Hirsch1, D. Shames10
  • 1Cancer Center, Univeristy of Colorado, 80045 - Aurora/US
  • 2Oncology, Oslo University Hospital, Oslo/NO
  • 3Biostatistics, Genentech Inc, San Francisco/US
  • 4Biostatistics, Genentech, San Francisco/US
  • 5Thoracic/head And Neck Medical Oncology, M.D. Anderson, Houston/US
  • 6Oncology Biomarker Development, Genentech, San Francisco/US
  • 7Pathology, Genentech, San Francisco/US
  • 8Pathology, Norwegian Radium Hospital, Oslo/NO
  • 9Oncology, Norwegian Radium Hospital, Oslo/NO
  • 10Oncology Biomarker Development, Genentech Inc, San Francisco/US



NaPi2b belongs to the type II family of sodium-dependent phosphate co-transporters, physiologically expressed in type II pneumocytes of lung and on the brush border membrane of small intestine. Increased expression of NaPi2b was recently described in ovary, thyroid and breast cancer. The aim of this study was to evaluate NaPi2b expression in lung cancer.


Immunohistochemistry using the 10H1 primary antibody (Genentech) was performed on two cohorts of treatment naïve resected NSCLC patients collected at MD Anderson, University of Texas, USA (training cohort, N = 415) and University of Oslo, Norway (testing cohort, N = 350). Moreover, 67 lung cancer cell lines were analyzed (51 non-small cell and 16 small cell lung cancer). EGFR and KRAS mutations were evaluated with the SnapShot assay. NaPi2b protein expression was scored using the H-score method (0-300). Expression was defined as high or low according to a H-score cut-off value of 200.


Patient characteristics did not differ significantly in the two cohorts. In the training and testing cohorts high levels of NaPi2b were detected in 48.4% and 64% of patients, respectively. Adenocarcinomas (AC) were found to express significantly higher levels of NaPi2b than squamous cell carcinoma (SqCC) (AC vs SqCC median H-score: 248 vs 11, p < 0.0001). An association between NaPi2b expression and overall survival was found in the training cohort (NaPi2b high vs low: 7.1 vs 5.3 years, p = 0.02). In the testing cohort the association between NaPi2b expression and survival was confined to the AC group (NaPi2b high vs low: 7.0 vs 3.9 years, p = 0.0002), while no difference was observed in SqCC. All cancer cell lines with NaPi2b expression were either EGFR mutated or ROS1 rearranged AC. Additional data on the correlation between NaPi2b and other biomarkers will be described in further detail.


NaPi2b is a prognostic marker in NSCLC and is strongly associated with important clinicopathological and biological variables such as histology and driver mutation status. Further studies are warranted to clarify the role of NaPi2b in tumor development and progression, as well as its association with driver mutations.


O.T. Brustugun received research funding from Roche, Astrazeneca and GlaxoSmithKline; Y. Xiao is a Genentech employee and owns stock in Roche Holdings; Y. Choi is en amployee of Genetech Inc and owns stock in Roche Holdings; Y. Wang is an employee of Genentech Inc and owns stock in Roche Holdings; R. Firestein is an employee of Genentech Inc and owns stock in Roche Holdings; Å. Helland received research funding from Roche, AstraZeneca and GlaxoSmithKline; F.R. Hirsch received research funding from Celgene, Genentech, Ventana, Lilly, Imclone and Amgen, and received compensation from Genentech/Roche, Novartis, Pfizer, Brystol-Meyers Squibb, Amgen and Lilly for partecipating in their advisory boards; D. Shames is an employee of Genetech Inc and owns stock in Roche Holdings. All other authors have declared no conflicts of interest.