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Abstract
BackgroundPodocalyxin (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.MethodsOf 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.ResultsMembranous 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)).ConclusionMembranous 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.
Highlights
Podocalyxin (PODXL) is a transmembrane sialomucin, whose aberrant expression and/or allelic variation associates with poor prognosis and unfavourable clinicopathological characteristics in different cancers
We recently showed by using a novel monoclonal antibody that high cytoplasmic expression of Podocalyxin-like 1 (PODXL) is a marker of poor prognosis in colorectal cancer (CRC) [21]
Immunohistochemical staining by the polyclonal antibody PODXL expression by the pAb was cytoplasmic in tumour cells, but in some cases a distinct membranous expression was seen, which did not always correlate with intensity of cytoplasmic expression
Summary
Podocalyxin (PODXL) is a transmembrane sialomucin, whose aberrant expression and/or allelic variation associates with poor prognosis and unfavourable clinicopathological characteristics in different cancers. Podocalyxin-like 1 (PODXL) was originally found in kidney podocytes [3], but it is expressed by vascular [4] and breast epithelium [5], and haematopoietic progenitors [6]. It is an anti-adhesive transmembrane glycoprotein that can be comprehensively sialyted and O-glycosylated. PODXL is recognised as a stem cell marker [8], closely related to CD34 and endoglycan It regulates cell morphology and adhesion through its connections to intracellular proteins and to extracellular ligands [9,10,11,12]. The role of PODXL in cancer is not fully understood, but it seems to participate in epithelial-mesenchymal transition [13], and it interacts with different mediators of metastasis [10,11,12,14,15]
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