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Investigating the concordance in molecular subtypes of primary colorectal tumors and their matched synchronous liver metastasis
Author(s) -
Schlicker Andreas,
Ellappalayam Architha,
Beumer Ines J.,
Snel Mireille H. J.,
Mittempergher Lorenza,
Diosdado Begona,
Dreezen Christa,
Tian Sun,
Salazar Ramon,
Loupakis Fotios,
Pietrantonio Filippo,
Santos Vivas Cristina,
MartinezVillacampa Maria Mercedes,
Villanueva Alberto,
Sanjuán Xavier,
Schirripa Marta,
Fassan Matteo,
Martinetti Antonia,
Fucà Giovanni,
Lonardi Sara,
Keilholz Ulrich,
Glas Annuska M.,
Bernards René,
Vecchione Loredana
Publication year - 2020
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.33003
Subject(s) - concordance , colorectal cancer , hazard ratio , medicine , metastasis , oncology , cancer , pathology , confidence interval
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, (90.2% and 98% concordance, respectively). In contrast, 40% to 70% of PT that were classified as mesenchymal‐like, based on the CMS and the TGFBa‐like signature, respectively, lost this phenotype in their matched LM (60.8% and 76.5% concordance, 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% CI = 1.5‐18.5, P = .0048; TGFBa‐like vs TGFBi‐like, HR = 2.5, 95% CI = 1.1‐5.6, 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.