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Role of RHAMM within the hierarchy of well-established prognostic factors in colorectal cancer
  1. I Zlobec1,
  2. L Terracciano1,
  3. L Tornillo1,
  4. U Günthert1,
  5. T Vuong2,
  6. J R Jass3,
  7. A Lugli1
  1. 1
    Institute of Pathology, University Hospital of Basel, Basel, Switzerland
  2. 2
    Department of Radiation Oncology, McGill University Health Centre, Montreal, Canada
  3. 3
    Department of Cellular Pathology, St. Mark’s Hospital, Middlesex, UK and Imperial College, London, UK
  1. Dr I Zlobec, Institute of Pathology, University Hospital of Basel, Schönbeinstrasse 40, Basel, CH-4031, Switzerland; izlobec{at}uhbs.ch

Abstract

Objective: To compare the independent prognostic effect of a panel of immunohistochemical protein markers in colorectal cancer (CRC) and determine their ranking among the established prognostic factors T stage, N stage, vascular invasion, tumour budding and tumour grade.

Design: A tissue microarray of 1420 CRCs was immunostained for 23 markers and mismatch repair (MMR) proteins. Immunoreactivity was assessed semi-quantitatively. Receiver operating characteristic (ROC) curves were used to determine cut-off scores for tumour marker positivity. Survival time was investigated for each marker in multivariable analysis with T stage, N stage, vascular invasion, tumour budding and tumour grade. The hazard ratio (HR) was used to compare the prognostic effect of each marker on 5 year survival.

Results: To the standard prognostic features, only six markers added independent prognostic information including receptor for hyaluronic acid mediated motility (RHAMM) (HR = 2.39 (1.88 to 3.05)), epidermal growth factor receptor (HR = 1.65 (1.31 to 2.09)), tumour infiltrating lymphocytes (HR = 0.7 (0.54 to 0.92)), urokinase plasminogen activator (HR = 1.38 (1.09 to 1.75)), Raf-1 kinase inhibitor protein (HR = 0.75 (0.58 to 0.96)) and mammalian sterile 20-like kinase 1 (MST1) (HR = 0.75 (0.58 to 0.95). Diffuse (>90% staining) expression of RHAMM ranked above T stage, vascular invasion, tumour budding and tumour grade in terms of adverse prognostic significance and was associated with distant metastasis (p = 0.012) and with worse outcome in patients with metastatic disease (p = 0.031).

Conclusions: The strong adverse effect of RHAMM on outcome in addition to its position within the hierarchy of well-established prognostic factors suggest that RHAMM should be considered a more important prognosticator than tumour grade, tumour budding and vascular invasion in patients with CRC.

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Footnotes

  • Funding: UG and LTe were supported by the Swiss Cancer League (OSC – 01265-08-2002) and IZ was supported by the Novartis Foundation, formerly the Ciba–Geigy Jubilee Foundation.

  • Competing interests: None.

  • Ethics approval: The use of tissue for this study was approved by the local Ethics Committee of the University Hospital of Basel on 3 November 2003.

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