Intratumoral heterogeneity in colorectal cancer: Can histology be used as a guidance for molecular testing?

611Background: Intratumour heterogeneity is a key challenge in colorectal cancer management. We have recently shown high levels of morphologic heterogeneity in microsatellite unstable (MSI) colorectal tumours (CRC). In this study we verified whether morphologic intratumour heterogeneity can be used as a guidance to test for molecular heterogeneity. Methods: 15 MSI CRCs tumour, characterized by a heterogenous morphology, were selected together with the associated metastasis. Macrodissection of the distinct morphologic tumour components was followed by MSI testing according to the Bethesda guidelines and Sanger sequencing for BRAF V600E mutations. In addition, 2 MSI CRC underwent macrodissection of the distinct morphologic components, followed by nanostring ncounter analysis. Results: MSI status varies between MSI-H and MSI-L in the primary tumours and 35% of the metastasis of MSI-H primary tumours presented as MSI-L or MSS. BRAF mutations status was constant throughout the primary tumours, but two BRAF mut...