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Systematic analysis of proteins from different signaling pathways in the tumor center and the invasive front of colorectal cancer

Karamitopoulou, Eva and Zlobec, Inti and Panayiotides, Ioannis and Patsouris, Efstratios S. and Peros, George and Rallis, George and Lapas, Christos and Karakitsos, Petros and Terracciano, Luigi M. and Lugli, Alessandro. (2011) Systematic analysis of proteins from different signaling pathways in the tumor center and the invasive front of colorectal cancer. Human pathology, Vol. 42, H. 12. pp. 1888-1896.

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Official URL: http://edoc.unibas.ch/dok/A6004130

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Abstract

In colorectal cancer, the functional impact of proteins from different signaling pathways varies between tumor center and tumor front. Our objective was to identify differential protein expression profiles between the tumor center and the tumor front of colorectal cancer. Twenty proteins from different signaling pathways (epidermal growth factor receptor [EGFR], phosphorylated extracellular signal regulated kinase [pERK], receptor for hyalouronic acid mediated motility [RHAMM], Raf-1 kinase inhibitor protein [RKIP], ?-catenin, E-cadherin, phosphorylated AK transforming [pAKT], p16, p21, Ki-67, B-cell Lymphoma-2 [BCL2], vascular endothelial growth factor, apoptosis protease activating factor 1 [APAF-1], mucin1 [MUC1], ephrin B2 receptor [EphB2], matrix metalloproteinase 7 [MMP7], phosphorylated mothers against decapentaplegic 2 [pSMAD2], caudal type homeobox transcription factor 2 [CDX2], Laminin5?2, and mammalian sterile 20-like kinase 1 [MST1]) involved in colorectal cancer progression were studied immunohistochemically on 220 well-characterized patients using a multiple-punch tissue microarray including 437 and 430 samples from the tumor center and the invasive front, respectively. Mean expression between the tumor center and the tumor front varied statistically significantly for pSMAD2, pERK, Raf-1 kinase inhibitor protein, E-cadherin, pAKT, BCL2, vascular endothelial growth factor, EphB2, matrix metalloproteinase 7, CDX2, Laminin5?2, MST1, and APAF-1. Overexpression of pAKT, BCL2, vascular endothelial growth factor, APAF-1, pERK, EphB2, Raf-1 kinase inhibitor protein, CDX2, E-cadherin, MST1 (P > .001 each), and pSMAD2 (P = .002) was more frequently observed in the tumor center, whereas matrix metalloproteinase 7 and Laminin5?2 (P > .001 each) overexpression was associated with the invasive front. In multivariate analysis, vascular endothelial growth factor (P > .001), Raf-1 kinase inhibitor protein (P = .009), and Laminin5?2 (P > .001) were the most relevant proteins with the multimarker phenotypes positive/positive/negative and negative/negative/positive being most discriminating between the tumor center and the tumor front. Moreover, the combination negative/negative/positive vascular endothelial growth factor/Raf-1 kinase inhibitor protein/Laminin5?2 at the tumor front was associated with vascular/lymphatic invasion (P = .014), distant metastasis (P = .019), higher tumor grade (P > .001), and poorer survival (P = .05). Our findings show that, in colorectal cancer progression, vascular endothelial growth factor overexpression seems to play a role in the tumor center, whereas Laminin5?2-positivity combined with Raf-1 kinase inhibitor protein loss is associated with tumor invasion at the front.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB
03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Molekulare Pathologie (Terracciano)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Molekulare Pathologie (Terracciano)
UniBasel Contributors:Terracciano, Luigi M. and Zlobec, Inti
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:W.B. Saunders
ISSN:0046-8177
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:27 Feb 2014 15:46
Deposited On:27 Feb 2014 15:46

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