Article

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

Hospital Italiano de Buenos Aires, Buenos Aires, Buenos Aires F.D., Argentina
Journal of Surgical Oncology (Impact Factor: 3.24). 02/2006; 93(2):151-60. DOI: 10.1002/jso.20413
Source: PubMed

ABSTRACT

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, beta-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.
Antigen expression was analyzed by immunohistochemistry. Prognostic evaluation was performed with the multivariate proportional hazards model.
We demonstrated a concomitant loss of E-cadherin and beta-catenin at membranous level and an abnormal accumulation of nuclear beta-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.
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.

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    • "the age, gender, ethnicity, Dukes' staging and lymph node status of the patients. Roca and coauthors found no significant correlation between MMP-7 and lymph node metastases which is consistent with our findings [34]. In contrast, Adachi and co-investigators reported that elevated levels of MMP-7 was significantly associated with lymph node metastases and advanced Dukes' stage suggesting its role in tumor metastases [15] [30]. "

    Full-text · Article · Jan 2014
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    • "the age, gender, ethnicity, Dukes' staging and lymph node status of the patients. Roca and coauthors found no significant correlation between MMP-7 and lymph node metastases which is consistent with our findings [34]. In contrast, Adachi and co-investigators reported that elevated levels of MMP-7 was significantly associated with lymph node metastases and advanced Dukes' stage suggesting its role in tumor metastases [15] [30]. "
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    ABSTRACT: Background: The purpose of the present study is to investigate the expression levels of STAT3, pSTAT3, MMP-7 and VEGF in colorectal adenocarcinoma, and also to determine association with the clinico-pathological parameters and co-expression of these genes. Methods: An immunohisto-chemical method was used to evaluate the expression of MMP-7 and VEGF genes in 93 archival tissues whereas STAT3 and pSTAT3 expression was determined in 75 cases. Results: Overexpres-sion of STAT3 was detected in 26.7% (20/75), pSTAT3 in 13.4% (10/75), MMP-7 in 38.8% (36/93) and VEGF in 59.2% (55/93) of the colorectal carcinomas. STAT3, MMP-7 and VEGF immunoposi-tivity were significantly correlated with poorly-differentiated tumors (P = 0.004; P = 0.03; P = 0.002, respectively) but not with other parameters. However, pSTAT3 immunostaining was not significantly associated with the clinico-pathological characteristics. Significant relationship was noted between overexpression of pSTAT3 and STAT3 (P < 0.001), pSTAT3 and VEGF (P = 0.044), pSTAT3 and MMP-7 (P = 0.003), and STAT3 and VEGF (P = 0.037) but marginal association was detected between STAT3 and MMP-7 (P = 0.057), and MMP-7 and VEGF (P = 0.052). Conclusion: Our data suggest that expression of these genes may have an important role in tumor dedifferen-tiation and may be useful as indicators of biologic aggressiveness. Co-expression of the bio-* Corresponding author. R. Naidu et al. 1176 markers by cancer cells may have important implications in colorectal cancer biology and could be useful biological markers of the malignant phenotype.
    Full-text · Article · Jan 2014 · Journal of Cancer Therapy
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    • "Down-regulation of E-cadherin in CRC is associated with malignant features. Loss of E-cadherin has been shown to be associated with tumor budding [18] and lymph node metastasis in CRC [19] and to predict disease recurrence and long-term survival in CRC [8,20,21]. In this study, loss of E-cadherin at the invasive margin of CRCs was associated with high tumor budding, perineural invasion, and a poor prognosis. "
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    ABSTRACT: Epithelial-to-mesenchymal transition (EMT) in cancers is related to metastasis, recurrence, and poor prognosis. We evaluated whether EMT-related proteins can act as prognostic biomarkers in colorectal cancer (CRC) patients. We evaluated the expression of E-cadherin, β-catenin, and S100A4 by immunohistochemistry (IHC) in 333 CRC tissues from the tumor center and invasive margin. Tumor budding, cell grade, tumor stage, type of tumor growth, peritumoral lymphocyte infiltration (TLI), and perineural- or lymphovascular invasion were evaluated as pathological parameters. mRNA levels of E-cadherin, N-cadherin, β-catenin, and S100A4 from 68 specimens from the same set were analyzed by real time quantitative RT-PCR. Loss of E-cadherin, nuclear β-catenin, and gain of S100A4 were higher in the invasive margin than in the tumor center. Loss of E-cadherin was associated with cell grade, macroscopic type, perineural invasion, and tumor budding, β-catenin with microsatellite instability and tumor site, and S100A4 with growth type, macroscopic type, AJCC stage, lymphovascular invasion, and perineural invasion. The aberrant expression of E-cadherin and S100A4 not β-catenin in the invasive margin was a significant and independent risk factor for disease-free and overall-survival by multivariate analysis, along with AJCC stage and perineural invasion. mRNA levels of β-catenin and S100A4 were correlated with the IHC findings at the tumor invasive margin. E-cadherin and N-cadherin showed a weak inverse correlation. The combination of loss of E-cadherin and gain of S100A4 in the tumor invasive margin can be used to stratify patients with the same AJCC stage into different survival groups. Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9398289629244673
    Full-text · Article · Jun 2013 · Diagnostic Pathology
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