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Pathology Research International
Volume 2012 (2012), Article ID 509348, 11 pages
Review Article

Genetic and Epigenetic Events Generate Multiple Pathways in Colorectal Cancer Progression

1Department of Biological, Geological and Environmental Sciences, University of Sannio, Via Port’Arsa 11, 82100 Benevento, Italy
2Department of Pathology, “Mater Salutis” Hospital, ULSS21 Legnago, Verona, Italy

Received 9 January 2012; Revised 15 May 2012; Accepted 21 May 2012

Academic Editor: Ka F. To

Copyright © 2012 Massimo Pancione et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Colorectal cancer (CRC) is one of the most common causes of death, despite decades of research. Initially considered as a disease due to genetic mutations, it is now viewed as a complex malignancy because of the involvement of epigenetic abnormalities. A functional equivalence between genetic and epigenetic mechanisms has been suggested in CRC initiation and progression. A hallmark of CRC is its pathogenetic heterogeneity attained through at least three distinct pathways: a traditional (adenoma-carcinoma sequence), an alternative, and more recently the so-called serrated pathway. While the alternative pathway is more heterogeneous and less characterized, the traditional and serrated pathways appear to be more homogeneous and clearly distinct. One unsolved question in colon cancer biology concerns the cells of origin and from which crypt compartment the different pathways originate. Based on molecular and pathological evidences, we propose that the traditional and serrated pathways originate from different crypt compartments explaining their genetic/epigenetic and clinicopathological differences. In this paper, we will discuss the current knowledge of CRC pathogenesis and, specifically, summarize the role of genetic/epigenetic changes in the origin and progression of the multiple CRC pathways. Elucidation of the link between the molecular and clinico-pathological aspects of CRC would improve our understanding of its etiology and impact both prevention and treatment.