Overexpression of the receptor for hyaluronic acid mediated motility is an independent adverse prognostic factor in colorectal cancer

Abstract

RHAMM, a member of the microtubule-associated protein family that interacts with the mitogen-activated protein kinase pathway, is associated with tumor progression, aggressive disease and shortened survival in several tumor types. This study aimed to determine the prognostic value of RHAMM in colorectal cancer (CRC). A series of 1420 unselected, nonconsecutive CRC resections were subdivided into three groups: (1) DNA mismatch repair (MMR)-proficient, (2) MLH1 negative and (3) presumed Lynch syndrome. Immunohistochemical analysis of RHAMM expression (0 vs 40%), increasing expression (increasing percentage positivity) and complete expression (100 vs o100%) was performed using tissue microarray technique and the results were correlated with clinicopathological parameters. Fifty-seven tissue samples of normal colonic mucosa were included as a control group. In a univariate analysis increasing and complete expression of RHAMM were associated with higher N stage (P ¼ 0.023 and 0.021) and worse survival (Po0.0001) in MMR-proficient CRC. Complete expression of RHAMM was associated with worse survival in presumed Lynch syndrome (P ¼ 0.016). In MLH1-negative CRC there was no association between RHAMM expression and the clinicopathological features. In a multivariate analysis, increasing RHAMM expression was an independent adverse prognostic factor in MMR-proficient CRC (Po0.0001) and complete expression in MMR-proficient CRC and presumed Lynch syndrome (Po0.0001 and P ¼ 0.031, respectively). Nuclear pERK expression was associated with increasing RHAMM expression in MMR-proficient CRC (P ¼ 0.012) and with complete RHAMM expression in presumed HNPCC (P ¼ 0.03). Increasing and complete RHAMM expressions are independent adverse prognostic factors in MMR-proficient CRC and presumed Lynch syndrome.

The effect of glycosaminoglycans on rat gametes in vitro and the associated signal pathway

“…Furthermore, there is a large body of evidence to show that HA and CD44 are active in many signal pathways (Kobayashi et al 2002, Roscic-Mrkic et al 2003, Bourguignon et al 2005, 2006, Lugli et al 2006, Shi et al 2006. The primer sequence (Kon et al 2006) for CD44 in RT-PCR targeted the transcript for the whole protein.…”

Multimarker phenotype predicts adverse survival in patients with lymph node‐negative colorectal cancer

“…On the basis of our previous findings, 11 of these markers were identified as significant and independent prognostic factors in MMR-proficient CRC and, thus, were selected for the current investigation. [10][11][12][13][14][15][16][17] uPA and uPAR also were included in FIGURE 1. Receiver-operating characteristic curves for protein markers that had discriminatory power for survival in lymph node-negative mismatch repairproficient colorectal cancer, namely, urokinase-type plasminogen activator (uPA) (A), uPA receptor (uPAR) (B), p27 (C), and CD8+ tumor infiltrating lymphocytes (D).…”

“…Of the protein markers that were chosen for this study, 11 were identified previously that had significant and independent prognostic value in MMR-proficient CRC. [10][11][12][13][14][15][16][17] …”

The candidate immunotherapeutical target, the receptor for hyaluronic acid-mediated motility, is associated with proliferation and shows prognostic value in B-cell chronic lymphocytic leukemia

“…[18][19][20] Therefore, we recently evaluated the influence RHAMM expression on the survival of acute myeloid leukemia patients using cDNA microarray technology. 21 However, in acute myeloid leukemia, RHAMM expression was associated with a trend towards prolonged survival.…”