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@ARTICLE{Alwers:144333,
      author       = {E. Alwers$^*$ and H. Bläker and V. Walter$^*$ and L.
                      Jansen$^*$ and M. Kloor and A. Arnold and J. Sieber-Frank
                      and E. Herpel and K. E. Tagscherer and W. Roth and J.
                      Chang-Claude$^*$ and H. Brenner$^*$ and M. Hoffmeister$^*$},
      title        = {{E}xternal validation of molecular subtype classifications
                      of colorectal cancer based on microsatellite instability,
                      {CIMP}, {BRAF} and {KRAS}.},
      journal      = {BMC cancer},
      volume       = {19},
      number       = {1},
      issn         = {1471-2407},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DKFZ-2019-01786},
      pages        = {681},
      year         = {2019},
      abstract     = {Competing molecular classification systems have been
                      proposed to complement the TNM staging system for a better
                      prediction of survival in colorectal cancer (CRC). However,
                      validation studies are so far lacking. The aim of this study
                      was to validate and extend previously published molecular
                      classifications of CRC in a large independent cohort of CRC
                      patients.CRC patients were recruited into a population-based
                      cohort study (DACHS). Molecular subtypes were categorized
                      based on three previously published classifications.
                      Cox-proportional hazard models, based on the same set of
                      patients and using the same confounders as reported by the
                      original studies, were used to determine overall,
                      cancer-specific, or relapse-free survival for each subtype.
                      Hazard ratios and confidence intervals, as well as
                      Kaplan-Meier plots were compared to those reported by the
                      original studies.We observed similar patterns of worse
                      survival for the microsatellite stable (MSS)/BRAF-mutated
                      and MSS/KRAS-mutated subtypes in our validation analyses,
                      which were included in two of the validated classifications.
                      Of the two MSI subtypes, one defined by additional presence
                      of CIMP-high and BRAF-mutation and the other by tumors
                      negative for CIMP, BRAF and KRAS-mutations, we could not
                      confirm associations with better prognosis as suggested by
                      one of the classifications. For two of the published
                      classifications, we were able to provide results for
                      additional subgroups not included in the original studies
                      (men, other disease stages, other locations).External
                      validation of three previously proposed classifications
                      confirmed findings of worse survival for CRC patients with
                      MSS subtypes and BRAF or KRAS mutations. Regarding MSI
                      subtypes, other patient characteristics such as stage of the
                      tumor, may influence the potential survival benefit. Further
                      integration of methylation, genetic, and immunological
                      information is needed to develop and validate a
                      comprehensive classification that will have relevance for
                      use in clinical practice.},
      cin          = {C070 / C120 / C020 / L101},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331 / I:(DE-He78)C120-20160331 /
                      I:(DE-He78)C020-20160331 / I:(DE-He78)L101-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31296182},
      pmc          = {pmc:PMC6624952},
      doi          = {10.1186/s12885-019-5842-7},
      url          = {https://inrepo02.dkfz.de/record/144333},
}