Abstract
Background/AimsEpithelial-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.MethodsWe 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.ResultsLoss 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.ConclusionsThe 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 slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9398289629244673
Highlights
The incidence of colorectal cancers (CRC) has been increasing in Korea since 1999
Loss of E-cadherin was related with cell grade (p = 0.050), macroscopic type (p = 0.014), perineural invasion (p = 0.037) and high tumor budding (p = 0.010)
Nuclear β-catenin expression was higher in microsatellite stable (MSS) than microsatellite instable (MSI) tumors (p = 0.004) and left CRCs than in right CRCs (p = 0.037)
Summary
The incidence of colorectal cancers (CRC) has been increasing in Korea since 1999. In 2009, CRC was the fourth most fatal cancer [1]. The 5-year survival rate of CRC overall has been reported to be as high as 71.3% [1], the survival rate in patients with recurrence is only 40%. The recurrence rate of stage I - III CRC patients who received curative resection has been reported to be 27.3% [2]. In addition to American Joint Committee on Cancer (AJCC) stage, biomarkers to predict recurrence are needed to select those patients who should be treated more aggressively. The growth pattern of the invasive margin, tumor budding, tumor grade, perineural invasion, and lymphovascular invasion have been reported to predict a poor prognosis [3,4]. Tumor buds are thought to be responsible for the subsequent steps in invasion and metastasis [5]
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