Prognostic value of E-cadherin, beta-catenin, MMPs (7 and 9), and TIMPs (1 and 2) in patients with colorectal carcinoma

• Published in: Journal of surgical oncology Vol. 93; no. 2; pp. 151 - 160
• Main Authors: Roca, Fernanda, Mauro, Laura V., Morandi, Ana, Bonadeo, Fernando, Vaccaro, Carlos, Quintana, Guillermo Ojea, Specterman, Sergio, de Kier JoffÉ, Elisa Bal, Pallotta, María Guadalupe, Puricelli, Lydia InÉs, Lastiri, JosÉ
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-02-2006
• Subjects: Adult; Aged; beta Catenin - biosynthesis; Biomarkers, Tumor - biosynthesis; Cadherins - biosynthesis; colorectal cancer; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; E-cadherin; Female; Humans; Male; Matrix Metalloproteinases - biosynthesis; metalloproteinases; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Retrospective Studies; Survival Analysis; TIMPs; Tissue Inhibitor of Metalloproteinase-1 - biosynthesis; Tissue Inhibitor of Metalloproteinase-2 - biosynthesis; Tissue Inhibitor of Metalloproteinases - biosynthesis; tumor marker
• ISSN: 0022-4790; 1096-9098
• DOI: 10.1002/jso.20413

Background and Objectives
Therapy of colorectal tumors (CRC) based on histology and clinical factors is insufficient to predict the evolution of each patient. The finding of molecular abnormalities able to differentiate subgroups of patients with bad prognosis will improve our ability to treat them successfully. Our purpose was to analyze retrospectively the prognostic input of E‐cadherin, β‐catenin, metalloproteinases (MMPs) (7 and 9), and tissue inhibitors of metalloproteinases (TIMPs) (1 and 2) in patients with a follow‐up period of 5 years.
Methods
Antigen expression was analyzed by immunohistochemistry. Prognostic evaluation was performed with the multivariate proportional hazards model.
Results
We demonstrated a concomitant loss of E‐cadherin and β‐catenin at membranous level and an abnormal accumulation of nuclear β‐catenin. Besides, we found that all MMPs and TIMPs studied were overexpressed in CRC tissue. There was no association between the expression of any of these molecules and the known clinical‐pathological parameters employed in CRC pathology. A multivariate analysis demonstrated that the overall survival could be independently predicted by the loss of E‐cadherin and the overexpression of TIMP‐2.
Conclusions
The expression of E‐cadherin and TIMP‐2 could be relevant in determining the prognosis of CRC patients and providing a more accurate mechanism for their classification. J. Surg. Oncol. 2006;93: 151–160. © 2006 Wiley‐Liss, Inc.