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Title: | High-resolution and quantitative spatial analysis reveal intra-ductal phenotypic and functional diversification in pancreatic cancer | Authors: | Michiels, Ellis Madhloum, Hediel Van Lint, Silke Messaoudi, Nouredin Kunda, Rastislav MARTENS, Sandrina Giron, Philippe Olsen, Catharina Lefesvre, Pierre Dusetti, Nelson |
Issue Date: | 2023 | Publisher: | WILEY | Source: | JOURNAL OF PATHOLOGY, 262 (1), p. 76-89 | Abstract: | A 'classical' and a 'basal-like' subtype of pancreatic cancer have been reported, with differential expression of GATA6 and different dosages of mutant KRAS. We established in situ detection of KRAS point mutations and mRNA panels for the consensus subtypes aiming to project these findings to paraffin-embedded clinical tumour samples for spatial quantitative analysis. We unveiled that, next to inter-patient and intra-patient inter-ductal heterogeneity, intraductal spatial phenotypes exist with anti-correlating expression levels of GATA6 and KRAS(G12D). The basal-like mRNA panel better captured the basal-like cell states than widely used protein markers. The panels corroborated the co-existence of the classical and basal-like cell states in a single tumour duct with functional diversification, i.e. proliferation and epithelial-to-mesenchymal transition respectively. Mutant KRAS(G12D) detection ascertained an epithelial origin of vimentin-positive cells in the tumour. Uneven spatial distribution of cancer-associated fibroblasts could recreate similar intra-organoid diversification. This extensive heterogeneity with functional cooperation of plastic tumour cells poses extra challenges to therapeutic approaches. (c) 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. | Notes: | Rooman, I (corresponding author), Vrije Univ Brussel, Laarbeeklaan 103, B-1090 Jette, Brussels, Belgium. ilse.rooman@vub.be |
Keywords: | molecular heterogeneity;mutation detection;spatial subtyping;pancreatic cancer;plasticity | Document URI: | http://hdl.handle.net/1942/41804 | ISSN: | 0022-3417 | e-ISSN: | 1096-9896 | DOI: | 10.1002/path.6212 | ISI #: | 001089263800001 | Rights: | 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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