564P - Association and prognostic interaction of podocalyxin like-protein with epidermal growth factor receptor alterations in colorectal cancer: A cohort...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Colon Cancer
Rectal Cancer
Translational Research
Presenter Anna Larsson
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors A.H. Larsson1, S. Wangefjord1, G. Emberger2, M. Sundström3, B. Nodin1, J. Eberhard1, K. Jirström1
  • 1Clinical Sciences Lund, Lund University, 22185 - Lund/SE
  • 2Pathology, Karolinska University Hospital, Stockholm/SE
  • 3Immunology, Genetics And Pathology, Uppsala University, Uppsala/SE

Abstract

Aim

Podocalyxin-like 1 (PODXL) is an anti-adhesive transmembrane glycoprotein and stem cell marker that has been demonstrated to be an independent factor of poor prognosis in colorectal cancer (CRC). The gene encoding PODXL is located to chromosome 7, which also harbours the gene for the epidermal growth factor receptor (EGFR). High expression of EGFR correlates with poor prognosis in CRC, and EGFR gene copy number (gcn) alterations with responsiveness to anti-EGFR drugs. In this study, we examined the associations between PODXL expression and EGFR expression and gcn alterations, as well as KRAS and BRAF mutations, in a large, prospective CRC cohort.

Methods

Using immunohistochemistry and brightfield dual-in situ hybridization, EGFR expression and EGFR gcn alterations (amplification or polysomy) was assessed in tumours from 557 incident CRC cases in the Malmö Diet and Cancer Study, previously analysed for immunohistochemical PODXL expression, KRAS and BRAF mutation status.

Results

Overexpression of PODXL was significantly associated with high EGFR expression (p < 0.001) and BRAF mutation (p < 0.001), but not with EGFR gcn alterations or KRAS mutation. High EGFR protein expression, but not gcn alterations, was an independent predictor of a reduced 5-year OS (HR= 1.78; 95% CI 1.26-2.94). Of note, the highest risk of death within 5 years was observed in patients with tumours displaying high expression of PODXL and EGFR (HR= 3.25; 95% CI 2.12-4.98, p for interaction =0.118) or high PODXL expression and EGFR gcn alterations (HR= 3.50; 95% CI 2.20-5.56, p for interaction = 0.014).

Conclusions

The results from this study demonstrate that overexpression of PODXL is associated with high EGFR expression and BRAF mutation in CRC. Moreover, a significant interaction of PODXL and EGFR alterations on the risk of death within 5 years was observed. These findings suggest a functional link between PODXL and the well-established oncogene EGFR, further corroborating the role of PODXL as a biomarker of poor prognosis in CRC and also indicating a possible involvement of PODXL in the responsiveness to anti-EGFR treatment, which may be of considerable clinical importance.

Disclosure

All authors have declared no conflicts of interest.