A comparative study of two PODXL antibodies in 840 colorectal cancer patients

BACKGROUND: Podocalyxin (PODXL) is a transmembrane sialomucin, whose aberrant expression and/or allelic variation associates with poor prognosis and unfavourable clinicopathological characteristics in different cancers. Membranous expression of PODXL has been suggested to be an independent marker of poor prognosis in colorectal cancer (CRC), and previously by an in-house monoclonal antibody, we showed that also cytoplasmic overexpression of PODXL predicts poor prognosis. The aim of this study was to compare two PODXL antibodies with different epitopes case-by-case in CRC patients. METHODS: Of 840 consecutively operated CRC patients from Helsinki University Central Hospital, PODXL expression by polyclonal HPA 2110 antibody was evaluated from 780. Associations of PODXL expression with clinicopathological parameters and the impact of PODXL expression on survival were assessed. Kappa-value was used to assess the comparability of the two antibodies. RESULTS: Membranous PODXL expression associated with unfavourable clinicopathological parameters and with higher risk for disease-specific death from CRC within 5 years (unadjusted hazard ratio (HR) = 1.90; 95% confidence interval (CI) (1.32-2.75); adjusted HR = 1.64; 95% CI (1.11-2.43)). The comparability of expressions by the two antibodies was low (kappa =0.219, standard error 0.060, p < 0.0001). Combination of two antibodies identified a group of patients with even worse prognosis (unadjusted HR = 6.00; 95% CI (3.27-13.0); adjusted HR = 2.14; 95% CI (1.12-4.07)). CONCLUSION: Membranous expression by the polyclonal PODXL antibody and cytoplasmic overexpression by the monocolonal PODXL antibody are both independent markers of poor prognosis, but they recognise different groups of patients, both of which have poor prognosis. The combined use of the antibodies reveals a group with an even worse prognosis. The biological reasons for the difference between antibodies warrant further studies.