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Pathways and Crossroads to Colorectal Cancer

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Pre-Invasive Disease: Pathogenesis and Clinical Management

Abstract

Colorectal tumorigenesis is one of the best known processes of cellular transformation in humans. Its characterization has moved ahead by leaps and bounds during the last three decades thanks to major advances in the fields of endoscopy, histology and molecular pathology. And as often happens when a human disease is subjected to in-depth investigation, what originally appeared to be a single entity turns out to include several distinct clinical, histologic, and molecular phenotypes. Among other things, tumor phenotypes can tell us a great deal about the route taken by the tumor cells on their journey toward malignancy. Not surprisingly, some tumors develop along pathways that are “heavily ­ trafficked” (and for this reason, relatively well known); others follow the “roads less traveled.” But if obstacles arise along the way, tumor cells are adept at exploiting alternative routes that permit them to continue their journey toward cancer, and these deviations can give rise to mixed phenotypes. These phenotypes are nonetheless consistent with the concept of carcinogenesis as a nonrandom – and therefore, predictable – process. Each pathway, each crossroads is the result of a specific set of genetic or epigenetic alterations. Many are already well defined, others are only partially characterized, and some are still in the realm of hypothesis. Thus far, we have fairly reliable maps of at least two of the major pathways to colorectal cancer, but with increasingly sophisticated molecular analysis of preinvasive lesions, there is little doubt that we will eventually identify variants of these pathways and uncover others whose existence was not even suspected.

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Abbreviations

ACFs:

aberrant crypt foci

APC:

adenomatous polyposis coli

CIN:

chromosomal instability

CIMP:

CpG island methylator phenotype

MMR:

DNA mismatch repair

FAP:

familial adenomatous polyposis

GCSPs:

goblet-cell serrated polyps

HP:

hyperplastic polyposis

IBD:

inflammatory bowel disease

MSI:

microsatellite instability

MVSPs:

microvesicular serrated polyps

SAs:

serrated adenomas

SSAs:

sessile serrated adenomas

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Acknowledgements

E.C. is supported by grants received by G.M. from the Swiss National Science Foundation. G.M. also gratefully acknowledges the generous financial support of the Zurich Cancer League. The authors wish to thank Luca Roncucci for photos illustrating the histologic features of ACFs, Jana Rojickova for editing the figures, and Marian Kent for editing the text.

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  1. Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland

    Giancarlo Marra

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  1. Elisa Cattaneo
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  2. Michael Baudis
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Correspondence to Giancarlo Marra .

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    Rebecca C. Fitzgerald

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Cattaneo, E., Baudis, M., Buffoli, F., Bianco, M.A., Zorzi, F., Marra, G. (2011). Pathways and Crossroads to Colorectal Cancer. In: Fitzgerald, R. (eds) Pre-Invasive Disease: Pathogenesis and Clinical Management. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6694-0_18

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