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Michiels, E.; Madhloum, H.; Lint, S. van; Messaoudi, N.; Kunda, R.; Martens, S.; ... ; Rooman, I.
2023
High-resolution and quantitative spatial analysis reveal intra-ductal phenotypic and functional diversification in pancreatic cancer
Article / Letter to editor
open access
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
.
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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. © 2023 The Authors.
The Journal of Pathology
published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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