Biomarker alterations associated with distinct patterns of metastatic spread in colorectal cancer
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ORIGINAL ARTICLE
Biomarker alterations associated with distinct patterns of metastatic spread in colorectal cancer M. Michl 1,2 & F. Taverna 3 & J. Kumbrink 3,4 & T. S. Schiergens 4,5 & V. Heinemann 1,2,4 & J. Engel 6,7 & T. Kirchner 3,4 & Jens Neumann 3,4 Received: 18 September 2020 / Revised: 25 November 2020 / Accepted: 1 December 2020 # The Author(s) 2020
Abstract Metastatic spread is the most important life-threatening feature of colorectal cancer and is supposed to be mainly driven by alterations in different carcinogenic pathways. The present study compared mutation and expression profiles of distinctive biomarkers in colorectal cancer patients with different clinical metastatic patterns. As for a case-control study, patients were matched according to T category, grading and primary tumour site. Overall, 246 patients with either exclusive lung metastasis (N = 82), exclusive liver metastasis (N = 82) or non-metastatic colorectal cancer (N = 82) were identified. Paraffin-embedded specimens were examined for mutations in the RAS and RAF genes and for the expression of β-catenin and CD133. Clinical endpoints were presence or absence of distant metastasis, formation of metastasis in lungs versus the liver and survival. MAPK pathway mutations in either the KRAS, NRAS or BRAF gene were associated with the development of lung metastasis (63.4%) compared to the control group (47.6%; p = 0.04). MAPK pathway alterations plus high β-catenin expression were associated with metastasis to the lungs but not to the liver (28.0% vs. 13.4%; p = 0.02). High CD133 expression correlated with the development of liver metastasis compared to the control group (30.5% vs. 14.6%; p = 0.02). This data indicates that different patterns of distant spread are associated with specific biomarker alterations and may represent different molecular subtypes of colorectal cancer. However, underlying mechanisms of metastasis formation in different anatomic sites remains unclear. Since knowledge of the anticipated site of distant spread would substantially impact clinical management, further research is needed to identify solid biomarkers for different metastatic patterns. Keywords Lung metastasis . Metastatic colorectal cancer . Biomarker . CD133 . β-catenin . MAPK pathway mutations
Introduction * Jens Neumann [email protected] 1
Department of Medicine III, University Hospital, LMU Munich, München, Germany
2
Comprehensive Cancer Center, University Hospital, LMU Munich, München, Germany
3
Institute of Pathology, Faculty of Medicine, LMU Munich, Thalkirchner Str. 36, D-81377 München, Germany
4
German Cancer Consortium (DKTK), German Cancer Research Centre (DKFZ), Heidelberg, Germany
5
Department of General, Visceral and Transplantation Surgery, University Hospital, LMU Munich, München, Germany
6
Munich Cancer Registry (MCR), Ludwig-Maximilians-University of Munich, Munich, Germany
7
Institute of Medical Informatics, Biometry and Epidemiology (IBE), Ludwig-Maximilians-University of Munich, München, Germany
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