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@ARTICLE{Blker:142857,
      author       = {H. Bläker and E. Alwers$^*$ and A. Arnold and E. Herpel
                      and K. E. Tagscherer and W. Roth and L. Jansen$^*$ and V.
                      Walter$^*$ and M. Kloor and J. Chang-Claude$^*$ and H.
                      Brenner$^*$ and M. Hoffmeister$^*$},
      title        = {{T}he {A}ssociation {B}etween {M}utations in {BRAF} and
                      {C}olorectal {C}ancer-{S}pecific {S}urvival {D}epends on
                      {M}icrosatellite {S}tatus and {T}umor {S}tage.},
      journal      = {Clinical gastroenterology and hepatology},
      volume       = {17},
      number       = {3},
      issn         = {1542-3565},
      address      = {New York, NY},
      publisher    = {Elsevier Science},
      reportid     = {DKFZ-2019-00487},
      pages        = {455 - 462.e6},
      year         = {2019},
      abstract     = {Colorectal tumors with mutations in BRAF and microsatellite
                      stability (MSS) have been associated with adverse outcomes
                      of patients. Combined tests for microsatellite
                      instability-high (MSI-H) and BRAF mutations might therefore
                      be used in risk assessment, particularly for patients with
                      stage II tumors. We investigate the stage-specific
                      prognostic value of combined testing for MSI-H and BRAF for
                      patients with colorectal cancer.We performed a retrospective
                      analysis of colorectal tumor samples collected from 1995
                      patients at 22 hospitals in Germany, between 2003 and 2010.
                      Samples were analyzed for MSI-H using an established
                      mononucleotide marker panel; BRAF mutations (BRAFV600E) were
                      detected by Sanger sequencing or in tissue microarray blocks
                      using immunohistochemistry. Cancers were assigned to
                      categories of having MSS without mutations in BRAF, MSS with
                      mutant BRAF, MSI-H without mutations in BRAF, and MSI-H with
                      mutant BRAF. We investigated the association between tumor
                      categories with clinical and pathologic features and
                      patient's overall, disease-specific, and recurrence-free
                      survival (median follow-up time, 5.1 y).Tumors were stage I
                      in 364 $(18\%),$ stage II in 678 $(34\%),$ stage III in 673
                      $(34\%),$ and stage IV $(14\%)$ in 280 patients.
                      Sixty-three percent of tumors were located in the colon and
                      $37\%$ in the rectum. Most tumors $(85\%)$ had MSS without
                      mutations in BRAF, $3\%$ had MSS with mutant BRAF, $7\%$ had
                      MSI-H without mutations in BRAF, $and 5\%$ had MSI-H with
                      mutant BRAF. In patients whose tumors were MSI-H, mutation
                      of BRAF did not significantly affect survival time. Patients
                      whose tumors had MSS with mutant BRAF had significantly
                      reduced overall survival (hazard ratio [HR], 2.16; $95\%$
                      CI, 1.54-3.04; P < .001), disease-specific survival (HR,
                      2.59; $95\%$ CI, 1.77-3.79; P < .001), and recurrence-free
                      survival (HR, 2.45; $95\%$ CI, 1.70-3.52; P < .001) than
                      patients whose tumors had MSS without BRAF mutation.
                      Although BRAF mutations in tumors with MSS were associated
                      with disease-specific survival of patients with stage III or
                      IV tumors (P < .001), these features did not affect survival
                      of patients with stage II tumors (P = .639).In an analysis
                      of almost 2000 patients with colorectal cancer, we found
                      BRAF mutations to reduce survival of patients in stage III
                      or IV (but not stage II) tumors with MSS. These findings do
                      not support testing stage I or II colorectal tumors for BRAF
                      mutations, although additional large studies are needed.},
      cin          = {C070 / C020 / L101 / L501},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331 / I:(DE-He78)C020-20160331 /
                      I:(DE-He78)L101-20160331 / I:(DE-He78)L501-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29660527},
      doi          = {10.1016/j.cgh.2018.04.015},
      url          = {https://inrepo02.dkfz.de/record/142857},
}