1634P - Inhibitor of differentiation-1 (Id1) and Id3 expression correlates with epithelial-mesenchymal transition (EMT)-related proteins (EMTrp) in non-sma...

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Lung and other Thoracic Tumours
Translational Research
Presenter Ignacio Gil-Bazo
Citation Annals of Oncology (2014) 25 (suppl_4): iv564-iv573. 10.1093/annonc/mdu359
Authors I. Gil-Bazo1, E. Castanon Alvarez2, I. Lopez3, M. Ponz-Sarvisé1, C.D. Rolfo4, M. Santisteban1, J.M. Lopez-Picazo5, J.P. Fusco1, L. Ceniceros2, J. Legaspi1, A. Soltermann6
  • 1Department Of Oncology, Clínica Universidad de Navarra, 31008 - Pamplona/ES
  • 2Oncology Department, Clinica Universitaria de Navarra, 31008 - Pamplona/ES
  • 3Laboratorio De Nuevas Dianas Terapéuticas, Centro de Investigación Médica Aplicada, 31008 - Pamplona/ES
  • 4Phase I- Early Clinical Trials Unit - Oncology Department, U.Z.A. University Hospital Antwerp, 2650 - Edegem/BE
  • 5Oncology Department, Clinica Universidad de Navarra, 31008 - Pamplona/ES
  • 6Institut Für Klinische Pathologie, Universitätsspital Zürich, 8091 - Zurich/CH

Abstract

Aim

We previously reported the prognostic impact of Id1 in all NSCLC stages and of the combined Id1/Id3 expression in stage III-N2 patients undergoing radical chemo-radiotherapy. Further, we found that Id1 expression in the tumor microenvironment is crucial for the development of liver metastasis from lung cancer in an in-vivo model. In other neoplasms, Id genes are considered to be regulators of EMT-facilitated metastasis. Here we study Id1 and Id3 combined expression in a large NSCLC cohort and its correlation with EMTrp and overall survival (OS).

Methods

Three tissue microarrays of 538 NSCLCs including 284 squamous-cell carcinomas (SCC) and 254 adenocarcinomas (AC) were stained by immunohistochemistry using the following antibodies: Sox10, Beta-catenin, E-cadherin, Vimentin, Slug, Podoplanin, S6, ERCC1, Id1 and Id3. Immunoreactivity was H-scored for intensity (range 0 to 3) multiplied by percentage of positive cells and computed by Spearman's Rho correlation test.

Results

Among SCC histology a significant positive correlation was observed between the combined expression of Id1 and Id3 and the expression of Sox10, Beta-catenin, E-Cadherin, Slug, Podoplanin and ERCC1. In the AC subset, significant positive correlations were found between Id1/Id3 and Beta-catenin, E-Cadherin, Vimentin, pS6, and ERCC1. As expected, Id1/Id3 expression showed a negative correlation with OS (r= -0.157; p=0.013).

Protein SCC AC
(n.s; not significant) r p value r p value
Sox10 0.146 0.018 n.s. n.s.
Beta-Catenin 0.218 0.001 0.161 0.01
E-cadherin 0.128 0.038 0.150 0.017
Vimentin n.s. n.s. 0.147 0.019
Slug 0.187 0.002 n.s. n.s.
Podoplanin 0.127 0.039 n.s. n.s.
S6 n.s. n.s. 0.150 0.014
ERCC1 0.265 0.001 0.185 0.003

Conclusions

In NSCLC, the combined expression of Id1 and Id3 negatively correlated with OS and positively with several key EMTrp, suggesting a possible key regulation of the EMT process favoring vessel infiltration and distant organ metastasis, respectively.

Disclosure

All authors have declared no conflicts of interest.