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TCF-3, 4 protein expression correlates with β-catenin expression in MSS and MSI-H colorectal cancer from HNPCC patients but not in sporadic colorectal cancers

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

The β-catenin–T-cell factor-4 (TCF-4) complex is the main control switch of cell proliferation and differentiation of normal and malignant intestinal cells. The aim of our study was to analyze the protein expression of components of the Wnt pathway in microsatellite stable (MSS) and highly unstable (MSI-H) sporadic and hereditary nonpolyposis colorectal cancer (HNPCC) in human colorectal cancers.

Methods

Sixty seven colorectal tumors comprising of 15 sporadic MSS, 12 sporadic microsatellite instability colorectal tumors and 40 tumors from HNPCC patients, of which 20 were MSS and 20 MSI-H, were analyzed for the expression of APC, β-catenin, and TCF-3, 4 proteins by immunohistochemistry.

Results

We found a significant difference in cytoplasmic APC expression frequency between sporadic MSS (52%) and HNPCC tumors (78%), whereas no difference was detected between MSI-H and MSS or HNPCC tumors. All tumor groups showed a similar pattern of decreased membranous staining and increased cytoplasmic and nuclear staining for β-catenin compared to normal cells. Moreover, the TCF-3, 4 protein expression was higher (43%) in HNPCC-associated MSS tumors compared to sporadic tumors (14%; analysis of variance (ANOVA) p < 0.05). For HNPCC tumors, the subcellular β-catenin expression (membranous, cytoplasmic, and nuclear) correlated with the nuclear TCF-3, 4 signal in MSS tumors (Spearman correlation p < 0.0007) and MSI-H tumors (Spearman correlation p < 0.0001).

Conclusion

We have shown a previously unknown difference in TCF-3, 4 protein expression between sporadic and HNPCC MSS tumors. In addition, we found no difference in nuclear β-catenin signal intensity, which may be caused by an alteration in Wnt pathway in MSS sporadic tumors by unknown mechanisms leading to lower TCF-3, 4 protein expression. This hypothesis has to be tested in future investigations.

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Acknowledgements

We thank Mrs. Monika Reichmann for her excellent technical support.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Surgical Research, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany

    Peter Balaz, Jens Plaschke, Stefan Krüger, Heike Görgens & Hans K. Schackert

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  1. Peter Balaz
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  2. Jens Plaschke
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  3. Stefan Krüger
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  5. Hans K. Schackert
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Correspondence to Hans K. Schackert.

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Balaz, P., Plaschke, J., Krüger, S. et al. TCF-3, 4 protein expression correlates with β-catenin expression in MSS and MSI-H colorectal cancer from HNPCC patients but not in sporadic colorectal cancers. Int J Colorectal Dis 25, 931–939 (2010). https://doi.org/10.1007/s00384-010-0959-9

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  • DOI: https://doi.org/10.1007/s00384-010-0959-9

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