TITLE

Role of RHAMM within the hierarchy of well-established prognostic factors in colorectal cancer

AUTHOR(S)
Zlobec, I.; Terracciano, L.; Tornillo, L.; Günthert, U.; Vuong, T.; Jass, J. R.; Lugli, A.
PUB. DATE
October 2008
SOURCE
Gut;Oct2008, Vol. 57 Issue 10, p1413
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
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.
ACCESSION #
34640825

 

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