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@ARTICLE{Dragomir:302021,
      author       = {M.-P. Dragomir$^*$ and V. Popovici and S. Schallenberg and
                      M. Čarnogurská and D. Horst$^*$ and R. Nenutil and F.
                      Bosman and E. Budinská},
      title        = {{A} quantitative tumor-wide analysis of morphological
                      heterogeneity of colorectal adenocarcinoma.},
      journal      = {The journal of pathology: clinical research},
      volume       = {11},
      number       = {4},
      issn         = {2056-4538},
      address      = {Chichester},
      publisher    = {Wiley},
      reportid     = {DKFZ-2025-01219},
      pages        = {e70034},
      year         = {2025},
      abstract     = {The intertumoral and intratumoral heterogeneity of
                      colorectal adenocarcinoma (CRC) at the morphologic level is
                      poorly understood. Previously, we identified morphological
                      patterns associated with CRC molecular subtypes and their
                      distinct molecular motifs. Here we aimed to evaluate the
                      heterogeneity of these patterns across CRC. Three
                      pathologists evaluated dominant, secondary, and tertiary
                      morphology on four sections from four different FFPE blocks
                      per tumor in a pilot set of 22 CRCs. An AI-based image
                      analysis tool was trained on these tumors to evaluate the
                      morphologic heterogeneity on an extended set of 161 stage
                      I-IV primary CRCs (n = 644 $H\&E$ sections). We found that
                      most tumors had two or three different dominant morphotypes
                      and the complex tubular (CT) morphotype was the most common.
                      The CT morphotype showed no combinatorial preferences.
                      Desmoplastic (DE) morphotype was rarely dominant and rarely
                      combined with other dominant morphotypes. Mucinous (MU)
                      morphotype was mostly combined with solid/trabecular (TB)
                      and papillary (PP) morphotypes. Most tumors showed medium or
                      high heterogeneity, but no associations were found between
                      heterogeneity and clinical parameters. A higher proportion
                      of DE morphotype was associated with higher T-stage,
                      N-stage, distant metastases, AJCC stage, and shorter overall
                      survival (OS) and relapse-free survival (RFS). A higher
                      proportion of MU morphotype was associated with higher
                      grade, right side, and microsatellite instability (MSI). PP
                      morphotype was associated with earlier T- and N-stage,
                      absence of metastases, and improved OS and RFS. CT was
                      linked to left side, lower grade, and better survival in
                      stage I-III patients. MSI tumors showed higher proportions
                      of MU and TB, and lower CT and PP morphotypes. These
                      findings suggest that morphological shifts accompany tumor
                      progression and highlight the need for extensive sampling
                      and AI-based analysis. In conclusion, we observed
                      unexpectedly high intratumoral morphological heterogeneity
                      of CRC and found that it is not heterogeneity per se, but
                      the proportions of morphologies that are associated with
                      clinical outcomes.},
      keywords     = {AI‐based image analysis (Other) / colorectal cancer
                      (Other) / heterogeneity (Other) / morphology (Other)},
      cin          = {BE01},
      ddc          = {610},
      cid          = {I:(DE-He78)BE01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40511583},
      doi          = {10.1002/2056-4538.70034},
      url          = {https://inrepo02.dkfz.de/record/302021},
}