TY - JOUR
T1 - Investigating the concordance in molecular subtypes of primary colorectal tumors and their matched synchronous liver metastasis.
AU - Schlicker, Andreas
AU - Ellappalayam, Architha
AU - Beumer, Ines J.
AU - Snel, Mireille H. J.
AU - Mittempergher, Lorenza
AU - Diosdado, Begona
AU - Dreezen, Christa
AU - Tian, Sun
AU - Salazar, Ramon
AU - Loupakis, Fotios
AU - Pietrantonio, Filippo
AU - Santos Vivas, Cristina
AU - Martinez-Villacampa, Maria Mercedes
AU - Villanueva, Alberto
AU - Sanjuán, Xavier
AU - Schirripa, Marta
AU - Fassan, Matteo
AU - Martinetti, Antonia
AU - Fucà, Giovanni
AU - Lonardi, Sara
AU - Keilholz, Ulrich
AU - Glas, Annuska M.
AU - Bernards, René
AU - Vecchione, Loredana
N1 - Place: United States
PY - 2020/10/1
Y1 - 2020/10/1
N2 - To date, no systematic analyses are available assessing concordance of molecular classifications between primary tumors (PT) and matched liver metastases (LM) of metastatic colorectal cancer (mCRC). We investigated concordance between PT and LM for four clinically relevant CRC gene signatures. Twenty-seven fresh and 55 formalin-fixed paraffin-embedded pairs of PT and synchronous LM of untreated mCRC patients were retrospectively collected and classified according to the MSI-like, BRAF-like, TGFB activated-like and the Consensus Molecular Subtypes (CMS) classification. We investigated classification concordance between PT and LM and association of TGFBa-like and CMS classification with overall survival. Fifty-one successfully profiled matched pairs were used for analyses. PT and matched LM were highly concordant in terms of BRAF-like and MSI-like signatures, (90.28 respectively). In contrast, 400like, based on the CMS and the TGFBa-like signature, respectively, lost this phenotype in their matched LM (60.86.5 respectively). This molecular switch was independent of the microenvironment composition. In addition, the significant change in subtypes was observed also by using methods developed to detect cancer cell-intrinsic subtypes. More importantly, the molecular switch did not influence the survival. PT classified as mesenchymal had worse survival as compared to nonmesenchymal PT (CMS4 vs CMS2, hazard ratio [HR] = 5.2, 95.5-18.5, P = .0048; TGFBa-like vs TGFBi-like, HR = 2.5, 95.1-5.6, P = .028). The same was not true for LM. Our study highlights that the origin of the tissue may have major consequences for precision medicine in mCRC.
AB - To date, no systematic analyses are available assessing concordance of molecular classifications between primary tumors (PT) and matched liver metastases (LM) of metastatic colorectal cancer (mCRC). We investigated concordance between PT and LM for four clinically relevant CRC gene signatures. Twenty-seven fresh and 55 formalin-fixed paraffin-embedded pairs of PT and synchronous LM of untreated mCRC patients were retrospectively collected and classified according to the MSI-like, BRAF-like, TGFB activated-like and the Consensus Molecular Subtypes (CMS) classification. We investigated classification concordance between PT and LM and association of TGFBa-like and CMS classification with overall survival. Fifty-one successfully profiled matched pairs were used for analyses. PT and matched LM were highly concordant in terms of BRAF-like and MSI-like signatures, (90.28 respectively). In contrast, 400like, based on the CMS and the TGFBa-like signature, respectively, lost this phenotype in their matched LM (60.86.5 respectively). This molecular switch was independent of the microenvironment composition. In addition, the significant change in subtypes was observed also by using methods developed to detect cancer cell-intrinsic subtypes. More importantly, the molecular switch did not influence the survival. PT classified as mesenchymal had worse survival as compared to nonmesenchymal PT (CMS4 vs CMS2, hazard ratio [HR] = 5.2, 95.5-18.5, P = .0048; TGFBa-like vs TGFBi-like, HR = 2.5, 95.1-5.6, P = .028). The same was not true for LM. Our study highlights that the origin of the tissue may have major consequences for precision medicine in mCRC.
M3 - Article
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 8
ER -