期刊论文详细信息
Diagnostic Pathology
Combined aberrant expression of E-cadherin and S100A4, but not β-catenin is associated with disease-free survival and overall survival in colorectal cancer patients
Seon Mee Park1  Sei Jin Youn1  Eun Jeoung Lee1  Rohyun Sung2  Soon Man Yoon1  Bo-Ra Son3  Taek-Gu Lee5  Meiying Ji1  Wun-Jae Kim4  Song Yi Choi2  Sang-Jeon Lee5 
[1] 4Department of Internal Medicine, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Republic of Korea;2Department of Pathology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Republic of Korea;5Department of Laboratory Medicine, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Republic of Korea;3Department of Urology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Republic of Korea;D1Department of Surgery, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Chungbuk 361-763, Republic of Korea
关键词: Colorectal cancer;    Tumor budding;    S100A4;    β-catenin;    E-cadherin;    Epithelial to mesenchymal transition;   
Others  :  806634
DOI  :  10.1186/1746-1596-8-99
 received in 2013-02-20, accepted in 2013-05-21,  发布年份 2013
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【 摘 要 】

Background/Aims

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.

Methods

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.

Results

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.

Conclusions

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 webcite

【 授权许可】

   
2013 Lee et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Jung KW, Park S, Kong HJ, Won YJ, Lee JY, Seo HG, Lee JS: Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2009. Cancer Res Treat 2012, 44:11-24.
  • [2]Tsai HL, Chu KS, Huang YH, Su YC, Wu JY, Kuo CH, Chen CW, Wang JY: Predictive factors of early relapse in UICC stage I-III colorectal cancer patients after curative resection. J Surg Oncol 2009, 100:736-743.
  • [3]Zlobec I, Lugli A: Prognostic and predictive factors in colorectal cancer. J Clin Pathol 2008, 61:561-569.
  • [4]Zlobec I, Molinari F, Martin V, Mazzucchelli L, Saletti P, Trezzi R, De Dosso S, Vlajnic T, Frattini M, Lugli A: Tumor budding predicts response to anti-EGFR therapies in metastatic colorectal cancer patients. World J Gastroenterol 2010, 16:4823-4831.
  • [5]Prall F: Tumour budding in colorectal carcinoma. Histopathology 2007, 50:151-162.
  • [6]Zlobec I, Lugli A: Epithelial mesenchymal transition and tumor budding in aggressive colorectal cancer: tumor budding as oncotarget. Oncotarget 2010, 1:651-661.
  • [7]Kalluri R, Neilson EG: Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest 2003, 112:1776-1784.
  • [8]Elzagheid A, Buhmeida A, Laato M, El-Faitori O, Syrjänen K, Collan Y, Pyrhönen S: Loss of E-cadherin expression predicts disease recurrence and shorter survival in colorectal carcinoma. APMIS 2012, 120:539-548.
  • [9]Brabletz T, Jung A, Hermann K, Gu¨nther K, Hohenberger W, Kirchner T: Nuclear overexpression of the oncoprotein b-catenin in colorectal cancer is localized predominantly at the invasion front. Pathol Res Pract 1998, 194:701-704.
  • [10]Sánchez-Tilló E, De Barrios O, Siles L, Cuatrecasas M, Castells A, Postigo A: β-catenin/TCF4 complex induces the epithelial-to-mesenchymal transition (EMT)-activator ZEB1 to regulate tumor invasiveness. Proc Natl Acad Sci U S A 2011, 108:19204-19209.
  • [11]Baldus SE, Mönig SP, Huxel S, Landsberg S, Hanisch FG, Engelmann K, Schneider PM, Thiele J, Hölscher AH, Dienes HP: MUC1 and nuclear ß-catenin are coexpressed at the invasion front of colorectal carcinomas and are both correlated with tumor prognosis. Clin Cancer Res 2004, 10:2790-2796.
  • [12]Horkko TT, Klintrup K, Makinen JM, Napankangas JB, Tuominen HJ, Makela J, Karttunen TJ, Makinen MJ: Budding invasive margin and prognosis in colorectal cancer-no direct association with beta-catenin expression. Eur J Cancer 2006, 42:964-971.
  • [13]Wangefjord S, Brändstedt J, Ericson Lindquist K, Nodin B, Jirström K, Eberhard J: Associations of beta-catenin alterations and MSI screening status with expression of key cell cycle regulating proteins and survival from colorectal cancer. Diagn Pathol 2013, 8:10. BioMed Central Full Text
  • [14]Boye K, Maelandsmo GM: S100A4 and metastasis: a small actor playing many roles. Am J Pathol 2010, 176:528-535.
  • [15]Flatmark K, Pedersen KB, Nesland JM, Rasmussen K, Aamodt G, Mikalsen S-O, Bjørnland K, Fodstad Ø, Mælandsmo GM: Nuclear localization of the metastasis-related protein S100A4 correlates with tumour stage in colorectal cancer. J Pathol 2003, 200:589-595.
  • [16]Gongoll S, Peters G, Mengel M, Piso P, Klempnauer J, Kreipe H, Von Wasielewski R: Prognostic significance of calcium binding protein S100A4 in colorectal cancer. Gastroenterology 2002, 123:1478-1484.
  • [17]Asayama Y, Taguchi Ki K, Aishima Si S, Nishi H, Masuda K, Tsuneyoshi M: The mode of tumour progression in combined hepatocellular carcinoma and cholangiocarcinoma: an immunohistochemical analysis of E-cadherin, alpha-catenin and beta-catenin. Liver 2002, 22:43-50.
  • [18]Zlobec I, Lugli A, Baker K, Roth S, Minoo P, Hayashi S, Terracciano L, Jass JR: Role of APAF-1, and peritumoral lymphocytic infiltration in tumour budding in colorectal cancer. J Pathol 2007, 212:260-268.
  • [19]Karamitopoulou E, Zlobec I, Patsouris E, Peros G, Lugli A: Loss of E-cadherin independently predicts the lymph node status in colorectal cancer. Pathology 2011, 43:133-137.
  • [20]Roca F, Mauro LV, Morandi A, Bonadeo F, Vaccaro C, Quintana GO, Specterman S, De Kier Joffé EB, Pallotta MG, Puricelli LI, Lastiri J: Prognostic value of E-cadherin, beta-catenin, MMPs (7 and 9) and TIMPs (1 and 2) in patients with colorectal carcinoma. J Surg Oncol 2006, 93:151-160.
  • [21]Ngan CY, Yamamoto H, Seshimo I, Ezumi K, Terayama M, Hemmi H, Takemasa I, Ikeda M, Sekimoto M, Monden M: A multivariate analysis of adhesion molecules expression in assessment of colorectal cancer. J Surg Oncol 2007, 95:652-662.
  • [22]Boye K, Nesland JM, Sandstad B, Mælandsmo GM, Flatmark K: Nuclear S100A4 is a novel prognostic marker in colorectal cancer. Eur J Cancer 2010, 46:2919-2925.
  • [23]Kho PS, Jankova L, Fung CL, Chan C, Clarke C, Lin BP, Robertson G, Molloy M, Chapuis PH, Bokey EL, Dent OF, Clarke S: Overexpression of protein S100A4 is independently associated with overall survival in stage C colonic cancer but only in cytoplasm at the advancing tumour front. Int J Colorectal Dis 2012, 27:1409-1417.
  • [24]Stein U, Arlt F, Walther W, Smith J, Waldman T, Harris ED, Mertins SD, Heizmann CW, Allard D, Birchmeier W, Schlag PM, Shoemaker RH: The metastasis-associated gene S100A4 is a novel target of beta-catenin/T-cell factor signaling in colon cancer. Gastroenterology 2006, 131:1486-1500.
  • [25]Iacopetta B: Aberrant DNA methylation: have we entered the era of more than one type of colorectal cancer ? Am J Pathol 2003, 162:1043-1045.
  • [26]Kawasaki T, Nosho K, Ohnishi M, Suemoto Y, Kirkner GJ, Dehari R, Meyerhardt JA, Fuchs CS, Ogino S: Correlation of beta-catenin localization with cyclooxygenase-2 expression and CpG island methylator phenotype (CIMP) in colorectal cancer. Neoplasia 2007, 9:569-577.
  • [27]Pino MS, Kikuchi H, Zeng M, Herraiz MT, Sperduti I, Berger D, Park DY, Iafrate AJ, Zukerberg LR, Chung DC: Epithelial to mesenchymal transition is impaired in colon cancer cells with microsatellite instability. Gastroenterology 2010, 138:1406-1417.
  • [28]Wang LM, Kevans D, Mulcahy H, O‘Sullivan J, Fennelly D, Hyland J, O‘Donoghue D, Sheahan K: Tumor budding is a strong and reproducible prognostic marker in T3N0 colorectal cancer. Am J Surg Pathol 2009, 33:134-141.
  • [29]Ludwig BC, Bernhard H, Arne S, Heinz-Joachim R, Felix B: N-cadherin is differentially expressed in histological subtypes of papillary renal cell carcinoma. Diagn Pathol 2012, 7:95. BioMed Central Full Text
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