Morphological Heterogeneity in Pancreatic Cancer Reflects Structural and Functional Divergence

Inter- and intratumor heterogeneity is an important cause of treatment failure. In human pancreatic cancer (PC), heterogeneity has been investigated almost exclusively at the genomic and transcriptional level. Morphological heterogeneity, though prominent and potentially easily assessable in clinica...

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Bibliographic Details
Published in:Cancers 2021-02, Vol.13 (4), p.895
Main Authors: Sántha, Petra, Lenggenhager, Daniela, Finstadsveen, Anette, Dorg, Linda, Tøndel, Kristin, Amrutkar, Manoj, Gladhaug, Ivar P, Verbeke, Caroline
Format: Article
Language:English
Subjects:
Biology
Caveolin
Caveolin-1
CD44 antigen
Cell adhesion & migration
Cell migration
Cell proliferation
Collagen
Collagen (type I)
Cytology
Extracellular matrix
Fibroblasts
Fibronectin
Gene expression
Genomics
Hyaluronic acid
Integrins
Investigations
Medical prognosis
Morphology
Pancreatic cancer
Stem cells
Stroma
Structure-function relationships
Transcription
Tumors
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Summary:Inter- and intratumor heterogeneity is an important cause of treatment failure. In human pancreatic cancer (PC), heterogeneity has been investigated almost exclusively at the genomic and transcriptional level. Morphological heterogeneity, though prominent and potentially easily assessable in clinical practice, remains unexplored. This proof-of-concept study aims at demonstrating that morphological heterogeneity reflects structural and functional divergence. From the wide morphological spectrum of conventional PC, four common and distinctive patterns were investigated in 233 foci from 39 surgical specimens. Twenty-six features involved in key biological processes in PC were analyzed (immuno-)histochemically and morphometrically: cancer cell proliferation (Ki67) and migration (collagen fiber alignment, MMP14), cancer stem cells (CD44, CD133, ALDH1), amount, composition and spatial arrangement of extracellular matrix (epithelial proximity, total collagen, collagen I and III, fibronectin, hyaluronan), cancer-associated fibroblasts (density, αSMA), and cancer-stroma interactions (integrins α2, α5, α1; caveolin-1). All features differed significantly between at least two of the patterns. Stromal and cancer-cell-related features co-varied with morphology and allowed prediction of the morphological pattern. In conclusion, morphological heterogeneity in the cancer-cell and stromal compartments of PC correlates with structural and functional diversity. As such, histopathology has the potential to inform on the operationality of key biological processes in individual tumors.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13040895