215P - Expression of AXL receptor and its ligand GAS6 in colorectal cancer (CRC)

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Colon Cancer
Rectal Cancer
Translational Research
Presenter Claudia Cardone
Citation Annals of Oncology (2014) 25 (suppl_4): iv58-iv84. 10.1093/annonc/mdu326
Authors C. Cardone1, G. Liguori2, T. Troiani3, A. Nappi4, N. Amoroso5, V.R. Iaffaioli6, C. Romano6, G. Botti2, D. Vitagliano7, G. Martini7, S. Napolitano7, F. Morgillo1, V. Sforza8, E. Giunta1, M. Di Maio9, F. De Vita1, F. Ciardiello10, E. Martinelli8
  • 1Division Of Medical Oncology, Department Of Experimental And Clinical Medicine And Surgery "f. Magrassi And A. Lanzara", Second University of Naples, 80131 - Naples/IT
  • 2Pathology Department, INT Fondazione Pascale, 80131 - Naples/IT
  • 3Dip. Medico Chirurgico Di Internistica, Second University of Naples, 80131 - Napoli/IT
  • 4Dipartimento Di Internistica F Magrassi A Lanzara, Second University of Naples, 80131 - Naples/IT
  • 5Fisica, Istituto Nazioanle di Fisica Nucleare, Bari/IT
  • 6Gastrointestinal Oncology, National Cancer Institute of Naples, Fondazione G.Pascale, 80131 - Naples/IT
  • 7Dipt. Di Internistica Clinica E Sperimentale, Second University of Naples, 80131 - Napoli/IT
  • 8Dipt. Di Internistica Clinica E Sperimentale, Second University of Naples, 80131 - Naples/IT
  • 9Clinical Trials Unit, Istituto Nazionale Tumori – I.R.C.C.S - Fondazione Pascale, 80131 - Napoli/IT
  • 10Dip. Medico Chirurgico Di Internistica, Seconda Università Studi di Napoli Policlinico Federico II, 80131 - Napoli/IT

Abstract

Aim

Background: the receptor tyrosin kinase AXL was identified as a key regulator of CRCcells migration and invasion, targeting AXL represents a potential approach in CRC treatment. Our aim was to assess AXL and GAS6 expression on tumor samples derived form patients with CRC.

Methods

From a cohort of 123 CRC patients (from 2003 to 2011) specimens from paraffin blocks were obtained and tissue microarrays (TMA) were performed. AXL and GAS6 expression level were assessed by immunohistochemistry (IHC) and FISH. By using non parametric, univariate and multivariate analysis, AXL and GAS6 expression was correlated with survival and clinicopathologic features.

Results

AXL expression was negative in 49/123 (39,8%) cases and positive in 74/123 cases (60,2%); 25 (33,8%) defined as low expression(1-19% of stained cells) and 49 (66.2%) as high expression(≥20%). AXL staining mostly displayed membrane positivity, with a small number of cases with cytosolic staining and one nuclear staining.Tumoral stroma and non-tumoral adjacent tissues were negative, whereas 10% of cases had endothelial cells positivity. GAS6 expression was also assessed in a small cohort of 73 CRC specimens. GAS6 IHC expression was found in 26/73 (35,1%) defined as low (1-29%) expression, 47 (67,1%) defined as high (≥30%). GAS6 staining was iuxta-membrane, 10% of samples displayed stromal posivity, indicating that the ligand can also be provided by the tumor microenvironment. A significantly correlation between AXL and GAS6 expression level (Pearson correlation coefficient 0.6 with a p <0.0001) was found, suggesting the presence of autocrine stimulatory loops within the tumour itself . FISH analysis was performed on 49 tumour cases. AXL was amplified in 4 cases(8%) with a ratio ranging from 2.0 to 2.3. We further correlated AXL and GAS6 expression with clinicopathologic features. AXL showed no correlation with T, N, M, stage, grading, pathologic features. Only GAS6 was statistically significant with respect to lymph node involvement (P < .002) and clinical stage (P < .004).

Conclusions

Conclusion: AXLand GAS6 were frequently overexpressed in CRC tumor specimen with 8% of AXL gene amplification, to our knowledge this is a first report. However no AXL or GAS6 prognostic role derived from our data.

Disclosure

All authors have declared no conflicts of interest.