Immunohistochemical detection of receptor tyrosine kinases c-kit, EGF-R, and PDGF-R in colorectal adenocarcinomas

Friederichs, Jan; Weyhern, Claus W. Hann von; Rosenberg, Robert D.; Doll, Dietrich; Busch, Raymonde; Lordick, Florian; Siewert, J. R.; Sarbia, Mario

doi:10.1007/s00423-009-0478-8

Cited by 11 publications

(8 citation statements)

References 33 publications

(46 reference statements)

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“…This suggests that expression of c-Kit in colon tumors is rare; thus, it is not a marker of choice in the colon. These findings are in accordance with Friederichs et al (38). Yet, the increased expression after several dose of chemotherapy can indicate a change in receptor expression pathway of stem cells, or an alteration in the tyrosine-kinase receptors.…”

Section: Discussionsupporting

confidence: 92%

Prognostic value of changes in the expression of stem cell markers in the peripheral blood of patients with colon cancer

Padín-Iruegas¹,

Herranz-Carnero²,

Aguín-Losada³

et al. 2013

Oncology Reports

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Cancer stem cells play an important role in carcinogenesis and resistance to treatment and may lead to metastasis. The isolation of circulating stem cells involves cell sorting based on the presence of cell surface markers. Many surface markers such as CD133, c-Kit, SOX, OCT4 and TWIST have been reported. In the present study, we determined the expression of different stem cell markers and their variation in expression at different stages of the treatment process. Samples of EDTA blood were collected from metastatic colorectal cancer patients, and circulating cancer stem cells were isolated for the analysis of the expression of stem cell markers using RT-PCR. These findings were correlated with the response to therapy. All statistical analyses were performed using the GraphPad Prism 5.03 software. Significant differences were found in the expression levels of the markers CD133, SOX2, OCT4 and TWIST1. No differences were found in c-Kit expression. Correlation in the expression levels of most of the markers was observed. Expression of CD133, OCT4, SOX2 and TWIST1 had a predictive value for colon cancer behavior. Evaluation of this stem cell gene expression panel may be useful for predicting the response during the process of treatment, and the relative easy access to samples facilitates this method. Moreover the correlation between CD133 and TWIST1 expression may be associated with tumor regrowth and metastatic relapse.

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Section: Discussionsupporting

confidence: 92%

Prognostic value of changes in the expression of stem cell markers in the peripheral blood of patients with colon cancer

Padín-Iruegas¹,

Herranz-Carnero²,

Aguín-Losada³

et al. 2013

Oncology Reports

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show abstract

“…Several immunohistochemical studies in colorectal cancer also detected a reduction in c-Kit that is associated with later stages of tumor development (29,30). However, studies on c-Kit expression in normal human colon and colon cancer tissue showed contradicting results: originally, c-Kit was detected throughout human adult and fetal tissues and in the colonic mucosa, submucosa, and intestinal smooth muscle layers (31).…”

Section: Discussionmentioning

confidence: 99%

c-Kit Is Suppressed in Human Colon Cancer Tissue and Contributes to L1-Mediated Metastasis

Gavert

Shvab

Sheffer³

et al. 2013

Cancer Research

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The transmembrane neural cell adhesion receptor L1 is a Wnt/b-catenin target gene expressed in many tumor types. In human colorectal cancer, L1 localizes preferentially to the invasive front of tumors and when overexpressed in colorectal cancer cells, it facilitates their metastasis to the liver. In this study, we investigated genes that are regulated in human colorectal cancer and by the L1-NF-kB pathway that has been implicated in liver metastasis. c-Kit was the most highly suppressed gene in both colorectal cancer tissue and the L1-NF-kB pathway. c-Kit suppression that resulted from L1-mediated signaling relied upon NF-kB, which directly inhibited the transcription of SP1, a major activator of the c-Kit gene promoter. Reconstituting c-Kit expression in L1-transfected cells blocked the biological effects conferred by L1 overexpression in driving motility and liver metastasis. We found that c-Kit expression in colorectal cancer cells is associated with a more pronounced epithelial morphology, along with increased expression of E-cadherin and decreased expression of Slug. Although c-Kit overexpression inhibited the motility and metastasis of L1-expressing colorectal cancer cells, it enhanced colorectal cancer cell proliferation and tumorigenesis, arguing that separate pathways mediate tumorigenicity and metastasis by c-Kit. Our findings provide insights into how colorectal cancer metastasizes to the liver, the most common site of dissemination in this cancer. Cancer Res; 73(18); 5754-63. Ó2013 AACR.

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“…To the Editor: We read with great interest the contribution by Friederichs and colleagues regarding immunohistochemical detection of the receptor tyrosine kinases c-kit, EGF-R, and PDGF-R in colorectal adenocarcinomas [1]. The authors showed EGF-R expression in only 15.3% of cases; emphasized that activity of tyrosine kinase inhibitors does not necessarily correlate with the tyrosine kinase expression of the tumors; showed that there is no correlation between EGF-R in colorectal cancer, clinical response to anti-EGF-R antibodies, and outcome; and that pretreatment selection of patients cannot be based on immunohistochemical expression of EGF-R.…”

mentioning

confidence: 99%

Expression of receptors tyrosine kinase c-kit and EGF-R in colorectal adenocarcinomas: is there a relationship with epithelial–mesenchymal transition during tumor progression?

Peparini

Caronna

Tellan

et al. 2009

Langenbecks Arch Surg

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Immunohistochemical detection of receptor tyrosine kinases c-kit, EGF-R, and PDGF-R in colorectal adenocarcinomas

Abstract: Our study confirms that expression of the tyrosine kinases c-kit and PDGF-R are rare in colorectal carcinomas and do not correlate with tumor stage.

Cited by 11 publications

References 33 publications

Prognostic value of changes in the expression of stem cell markers in the peripheral blood of patients with colon cancer

Prognostic value of changes in the expression of stem cell markers in the peripheral blood of patients with colon cancer

c-Kit Is Suppressed in Human Colon Cancer Tissue and Contributes to L1-Mediated Metastasis

Expression of receptors tyrosine kinase c-kit and EGF-R in colorectal adenocarcinomas: is there a relationship with epithelial–mesenchymal transition during tumor progression?

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