Are There Biochemical and Molecular Biological Factors to Distinguish the Rectal Cancer by the Colon Cancer?
Empirically, different strategies have evolved for the treatment of locally advanced colon cancer (surgery followed by adjuvant chemotherapy) compared to locally advanced rectal cancer (neoadjuvant radio- or radiochemotherapy followed by total mesorectal
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Ulrich T. Hacker and Pierre Laurent-Puig
Empirically, different strategies have evolved for the treatment of locally advanced colon cancer (surgery followed by adjuvant chemotherapy) compared to locally advanced rectal cancer (neoadjuvant radio- or radiochemotherapy followed by total mesorectal excision followed by adjuvant chemotherapy). These differences are mostly attributable to the anatomical situation which poses an increased risk of local recurrence in locally advanced rectal cancer compared to colon cancer. On the other hand, in the metastatic setting, the treatment strategies are very much the same for colon carcinomas and rectum carcinomas, and the clinical outcome is generally similar [8]. Based on differences that exist between the normal right and left colon with respect to embryonic origin (midgut vs. hindgut) and some histological features [7], the question was raised whether colon cancer can be distinguished from rectal cancer based on molecular and/or biochemical differences.
U.T. Hacker (*) University Medicine Leipzig, University Cancer Center Leipzig (UCCL), Liebigstraße 20, 04103 Leipzig, Germany e-mail: [email protected] P. Laurent-Puig Université Paris Descartes, 45 rue des Saints-Pères, Paris 75006, France e-mail: [email protected]
Pathways of carcinogenesis in colorectal cancer Two major pathways are fundamentally involved in the pathogenesis of colorectal cancer. The chromosomal instability phenotype (CIN phenotype) is characterized by a pattern of genomic instability resulting in aneuploidy and a wide range of chromosomal gains and losses [9]. This pathway accounts for about 85% of colorectal cancers, and the frequency of DNA mutations in this group is generally low. In contrast, 15% of colorectal cancers show defective function of DNA mismatch repair (dMMR) mechanisms resulting in high frequencies of mutations. Consequently, a hallmark of this group of colorectal cancers is microsatellite instability (MSI) [2]. About one third of dMMR, highly microsatellite instable (MSIhigh) colorectal cancers, arise based on hereditary mutations within the group of mismatch repair genes MLH1, MLH3, MSH2, MSH3, MSH6, or PMS2 leading to inactivation of the respective proteins. On the other hand, about two third of MSIhigh colorectal cancers arise sporadically [12]. Clinically, this group is characterized by older age at diagnosis, female predominance, right-sided location, poor differentiation, mucinous and inflammatory features, and an increased frequency of BRAF mutations, which in this setting do not confer a dismal prognosis. Another classification system is related to the methylation status of the tumors at different defined positions of the genome within CpG islands resulting in CpG island methylator
© Springer-Verlag Berlin Heidelberg 2018 V. Valentini et al. (eds.), Multidisciplinary Management of Rectal Cancer, https://doi.org/10.1007/978-3-319-43217-5_59
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U.T. Hacker and P. Laurent-Puig
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phenotype (CIMP) high (CIMP-H) vs. CIMP low (CIMP-L). T
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