Overexpression of the receptor for hyaluronic acid mediated motility is an independent adverse prognostic factor in colorectal cancer.
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 >0%), increasing expression (increasing percentage positivity) and complete expression (100 vs <100%) 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=0.023 and 0.021) and worse survival (P<0.0001) in MMR-proficient CRC. Complete expression of RHAMM was associated with worse survival in presumed Lynch syndrome (P=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 (P<0.0001) and complete expression in MMR-proficient CRC and presumed Lynch syndrome (P<0.0001 and P=0.031, respectively). Nuclear pERK expression was associated with increasing RHAMM expression in MMR-proficient CRC (P=0.012) and with complete RHAMM expression in presumed HNPCC (P=0.03). Increasing and complete RHAMM expressions are independent adverse prognostic factors in MMR-proficient CRC and presumed Lynch syndrome.
Lugli
Alessandro
A
Department of Pathology, McGill University, Duff Medical Building, Montreal, QC, Canada. alugli@po-box.mcgill.ca
Zlobec
Inti
I
Günthert
Ursula
U
Minoo
Parham
P
Baker
Kristi
K
Tornillo
Luigi
L
Terracciano
Luigi
L
Jass
Jeremy R
JR
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D016326:Extracellular Matrix Proteins; C094443:G-T mismatch-binding protein; D018960:Hyaluronan Receptors; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C098946:hyaluronan-mediated motility receptor; D048049:Extracellular Signal-Regulated MAP Kinases; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein