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D Horst
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ABSTRACT: Despite inactivating APC mutations, colorectal cancers express the WNT-effector protein β-catenin in a heterogeneous pattern, with strong nuclear expression confined to a fraction of tumor cells, often only at the tumor's leading edge. WNT-reporter constructs allow separation of these tumor cells with highest WNT/β-Catenin activity, which also express high levels of several putative cancer stem cell antigens. Unexpectedly however, these cells do not show exclusive tumorigenicity in xenograft experiments, thus questioning their general stemness phenotype. Instead, there appears to be significant plasticity between both tumor cells with high and low WNT/β-Catenin activity because both cell types can form tumors which again show mixed populations. Furthermore, WNT/β-Catenin activity in colon cancer cells can be modulated by MAPK signaling thus revealing a means of how other signaling pathways contribute to WNT signaling plasticity in colon cancer.
Der Pathologe 09/2012; · 0.67 Impact Factor
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ABSTRACT: The RNASE III endonuclease Dicer is one of the key enzymes of microRNA biogenesis. The influence of Dicer-expression in tumour cells on the prognosis of patients with several cancers has been studied with controversial results among different cancer types. To date no one has examined the effect of this biomarker on survival in colorectal carcinoma. Thus, we aimed to study the influence of Dicer expression on survival in colorectal cancer.
We performed immunohistochemical analyses on formalin-fixed paraffin embedded (FFPE) cancer tissue with an antibody against the Dicer protein. Tumour material from 237 cases was available from patients with colorectal adeonocarcinomas with moderate differentiation (G2) and without evidence of lymph-node (N0) or distant metastasis (M0). Sixty-four cases were in T2 and 173 in T3 stages. A tissue microarray (TMA) was constructed with each tumour in triplicate. Each tumour was assigned to a scoring scale of 0-3, depending on the cytoplasmatic expression of Dicer. A Kaplan-Maier analysis was performed and the log-rank test was used for significance levels by using SPSS v.17 software.
The expression of Dicer in colorectal carcinoma shows a strong association with poor survival (cancer specific survival=CSS, p<0,001) as well as with reduced progression free survival (PFS, p<0,001). In the group with no Dicer staining there was no recorded relapse (0/15) compared with 10/18 relapses in the group with the strongest staining of Dicer.
Strong expression of the central microRNA biosynthesis enzyme Dicer predicts poor prognosis in patients with colorectal cancer. This is in line with investigations on prostate cancer. Contradictory, in breast, lung and ovary cancer Dicer has been shown to be a marker of good prognosis. Further studies on the cellular functions of Dicer need to address these issues.
European journal of cancer (Oxford, England: 1990) 02/2011; 47(9):1414-9. · 4.12 Impact Factor
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British Journal of Dermatology 04/2009; 160(6):1353-6. · 3.67 Impact Factor
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ABSTRACT: Colon cancer cells have previously been demonstrated to contain a subpopulation of CD133+ tumour cells that have the ability to initiate tumour growth and are thus referred to as colon cancer-initiating cells or colon cancer stem cells (CSCs). As CD133 is currently one of the best markers to characterise colon CSCs, we analysed CD133+ tumour cells in colorectal cancer specimens using immunohistochemistry. We show that CD133 detection is specific and that the CD133 antigen is localised on the glandular-luminal surface of colon cancer cells, whereas undifferentiated tumour cells at the front of invasion are CD133-. In addition, CD133+ cells are characterised in situ by lack of CK20 expression, whereas they are positive for EpCAM. Moreover, we show that CD133 expression in colorectal cancer is an independent prognostic marker that correlates with low survival in a stratified patient collective. Our results indicate that in colorectal cancer, the CD133+ tumour cells can be detected by immunohistochemistry, which facilitates their further characterisation in situ.
British Journal of Cancer 10/2008; 99(8):1285-9. · 5.04 Impact Factor
