539P - Ptk7 overexpression is associated with reduced metastasis-free survival (MFS) in colorectal cancer

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Colon Cancer
Rectal Cancer
Translational Research
Presenter Anthony Gonçalves
Authors A. Gonçalves1, A. Lhoumeau2, G. Monges3, J. Delpero4, J.L. Raoul2, J. Borg2
  • 1Medical Oncology, Institut Paoli-Calmettes, 13009 - Marseille/FR
  • 2Molecular Pharmacology, Institut Paoli-Calmettes, Marseille/FR
  • 3Biopathology, Institut Paoli-Calmettes, Marseille/FR
  • 4Surgical Oncology, Institut Paoli-Calmettes, Marseille/FR

Abstract

Background

Protein tyrosine kinase-7 (PTK7) is a receptor tyrosine kinase (TK), with no identified natural ligand and a catalytically inactive intracellular TK domain. PTK7 expression is up-regulated in many human cancers, including colorectal cancer (CRC), but little is known about its role in cancer biology. Here, we have examined PTK7 protein expression in tumor and matched normal tissues from CRC patients by immunohistochemistry (IHC) and addressed the phenotypic impact of PTK7 down-regulation in CRC cell lines.

Methods

A TMA containing both tumor and matched normal tissues was built from a cohort of 192 patients with CRC collected between 1990 and 1998 at the Institut Paoli-Calmettes, Marseille, France. PTK7 expression was analyzed by IHC using polyclonal goat antibody anti-CC4 (R&D systems, USA). Percentage of stained cells was measured and staining intensity was scored as 0 (absent), 1 (weak), 2 (moderate) and 3 (strong). PTK7-expressing CRC cell lines were transfected with PTK7- or control- shRNA and evaluated for cell proliferation, cytotoxic-induced apoptosis and cell migration.

Results

Patient population had the following characteristics: median age, 63 ys (range 29-89); sex ratio = male (52%), female (48%); site = colon (90%), rectum (10%); stage = I-III (64%), IV (36%); median follow-up = 104 months. Staining intensity (0-1 = 65% of cases, 2 = 19% of cases, 3 =16% of cases, in tumor tissues versus 0-1 = 86% of cases, 2 = 11% of cases, 3= 3% of cases, in normal tissues; p = 1,91.10-8) as well as average percentage of stained cells (30% in tumor tissues versus 2% in normal tissues; p = 5.74.10-14) were higher in tumor compared to normal tissues. In stage I-III population (n = 122), 5-year MFS was lower in PTK7-positive (>10% of cells stained with intensity > 2) compared to PTK7-negative CRC (54% [95%CI: 38-75%] versus 75% [95%CI: 65-88%], p = 0.034, log-rank test). This impact was maintained in multivariate analysis and similar trends were observed in overall survival, while not reaching statistical significance. In vitro, PTK7 inhibition by shRNA significantly reduced cell migration.

Conclusion

PTK7 protein is overexpressed in CRC and is associated with reduced MFS, possibly due to an impact on cell migration.

Disclosure

All authors have declared no conflicts of interest.