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Open Access Research article

Podocalyxin is a marker of poor prognosis in colorectal cancer

Tuomas Kaprio12*, Christian Fermér3, Jaana Hagström25, Harri Mustonen1, Camilla Böckelman12, Olle Nilsson4 and Caj Haglund12

Author Affiliations

1 Department of Surgery, Helsinki University Central Hospital, PO Box 440, 00029 Helsinki HUS, Finland

2 Research Programs Unit, Translational Cancer Biology, University of Helsinki, Helsinki, Finland

3 Fujirebio Diagnostics AB, Elof Lindälvs gata 13, SE-414 58 Göteborg, Sweden

4 Onson Consulting, Södra vägen 2, SE-412 54 Göteborg, Sweden

5 Department of Pathology, Haartman Institute, University of Helsinki and HUSLAB, Helsinki FIN-00014 HY, Finland

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BMC Cancer 2014, 14:493  doi:10.1186/1471-2407-14-493

Published: 8 July 2014

Abstract

Background

Over two decades ago, a proposal was that two different colorectal cancer (CRC) entities existed, based on tumour location either proximal (right) or distal (left) of the splenic flexure. Proximal and distal tumours exhibit different clinical, epidemiological, and biological characteristics. Improvement of the prognostic evaluation of CRC requires new molecular markers. Podocalyxin-like 1 (PODXL), an anti-adhesive transmembrane sialomucin, is associated with an aggressive tumour phenotype and poor prognosis. For colorectal cancer, it has been suggested to be a marker of poor prognosis. The aim of this study was to investigate the role of PODXL in CRC by use of a novel monoclonal antibody.

Methods

In 1983–2001, 840 consecutive colorectal cancer patients were treated at Helsinki University Central Hospital, of whom 767 were successfully scored for PODXL immunohistochemical expression from tumour tissue microarrays by use of a novel monoclonal in-house antibody. Associations of PODXL expression and tumour location with other clinicopathological variables were explored by Fisher’s exact-test, linear-by- linear association test, and binary logistic regression. Survival analyses were done by the Kaplan-Meier method and Cox proportional hazards model.

Results

PODXL protein expression was high in 44 (5.7%) specimens. High expression associated strongly with poor differentiation (p < 0.0001), advanced stage (p = 0.011), and location of the tumour in the right hemicolon (RHC) (p < 0.001). Tumours of the RHC were more poorly differentiated (p < 0.0001) and showed higher PODXL expression (p < 0.001).

High PODXL expression associated significantly with higher risk for disease-specific death from CRC (hazard ratio (HR) = 2.00; 95% confidence interval (CI) 1.31–3.06, p = 0.001) and also in the subgroups of left hemicolon (LHC) cancers (HR = 2.60; 95% CI 1.45–4.66, p = 0.001) and rectal cancers (HR = 3.03; 95% CI 1.54–5.60, p = 0.001). Results remained significant in multivariable analysis (respectively, HR = 1.82; 95% CI 1.15–2.86, p = 0.01; HR = 2.59; 95% CI 1.41–4.88, p = 0.002; and HR = 2.69; 95% CI 1.30–5.54, p = 0.007).

Conclusion

Podocalyxin was an independent factor for poor prognosis in colorectal cancer and in the subgroups of left hemicolon and rectum. This is, to our knowledge, the first evidence of such difference in PODXL expression, its function possibly being dependent upon tumour location.

Keywords:
Colorectal cancer; Prognosis; Podocalyxin; Immunohistochemistry