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New time-dependent approach to analyze the prognostic significance of immunohistochemical biomarkers in colon cancer and diffuse large B-cell lymphoma
  1. Heiner Adams (heinera{at}gmx.de)
  1. Institute of Pathology, University Hospital of Basel, Basel, Switzerland
    1. Alexandar Tzankov (atzankov{at}uhbs.ch)
    1. Institute of Pathology, University Hospital of Basel, Basel, Switzerland
      1. Alessandro Lugli (alugli{at}uhbs.ch)
      1. Institute of Pathology, University Hospital of Basel, Basel, Switzerland
        1. Inti Zlobec (izlobec{at}uhbs.ch)
        1. Institute of Pathology, University Hospital of Basel, Basel, Switzerland

          Abstract

          Aims: Receiver operating characteristic (ROC) curve analysis is a well-established method to study the accuracies of biological markers. It may, however, be suboptimal for analyzing outcomes over time, such as prognosis. Here, we explore the clinical value of time-dependent ROC curve analysis for improving the identification of high-risk patients with colon cancers and diffuse large B-cell lymphomas (DLBCL).

          Methods: Using tissue microarrays, immunohistochemistry was performed on two matched sets (N = 469, each) of colon cancers (p53, CD8+ tumour infiltrating lymphocytes (TILs), MST1, MUC2 and uPAR) and on 208 DLBCL (Bcl2, Bcl6, CD10, FOXP1 and Ki67). The area under the curve (AUC)-over-time plots, cut-off scores for tumor marker positivity, and Kaplan-Meier survival curves were analyzed.

          Results: With the exception of uPAR, all markers were most accurate within the first 18 months following diagnosis. Expression of p53 (AUC=0.75), uPAR (AUC=0.64), Bcl2 (AUC=0.58) and FOXp1 (AUC=0.68) were linked to more aggressive tumours while TILs (AUC=0.38), MST1 (AUC=0.39), MUC2 (AUC=0.38), Bcl6 (AUC=0.4), CD10 (AUC=0.49) and Ki67 (AUC=0.41) were predictive of improved survival. Cut-off scores for markers at their peak accuracies as well as survival time differences were reproducible between colon cancer groups. Only FOXp1 at its optimal cut-off of 60% had significant effects on survival in DLBCL (p=0.019).

          Conclusions: Time-dependent ROC curve analysis is a novel tool for identifying potential immunohistochemical prognostic markers across varying follow-up times. Use of this tool could facilitate the identification of high-risk patients not only with colon cancer and DLBCL but with a range of other tumour types.

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