J Cancer 2021; 12(24):7488-7497. doi:10.7150/jca.63633 This issue

Research Paper

Epithelial-to-Mesenchymal Transition in Pancreatic Cancer is associated with Restricted Water Diffusion in Diffusion-Weighted Magnetic Resonance Imaging

Philipp Mayer1, Anne Kraft2, Wilfried Roth2, Thilo Hackert3, Frank Bergmann4,5, Hans-Ulrich Kauczor1, Verena Steinle1, Ekaterina Khristenko1, Miriam Klauss1, Matthias M. Gaida2,6,7✉

1. Clinic for Diagnostic and Interventional Radiology, Heidelberg University Hospital, 69120 Heidelberg, Germany.
2. Institute of Pathology, University Medical Center Mainz, JGU-Mainz, 55131 Mainz, Germany.
3. Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany.
4. Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany.
5. Clinical Pathology, Klinikum Darmstadt GmbH, 64283 Darmstadt, Germany.
6. Research Center for Immunotherapy, University Medical Center Mainz, JGU-Mainz, 55131 Mainz, Germany.
7. Joint Unit Immunopathology, Institute of Pathology, University Medical Center, JGU-Mainz and TRON, Translational Oncology at the University Medical Center, JGU-Mainz, 55131 Mainz, Germany.

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Citation:
Mayer P, Kraft A, Roth W, Hackert T, Bergmann F, Kauczor HU, Steinle V, Khristenko E, Klauss M, Gaida MM. Epithelial-to-Mesenchymal Transition in Pancreatic Cancer is associated with Restricted Water Diffusion in Diffusion-Weighted Magnetic Resonance Imaging. J Cancer 2021; 12(24):7488-7497. doi:10.7150/jca.63633. Available from https://www.jcancer.org/v12p7488.htm

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Abstract

Graphic abstract

Purpose: This study aimed to evaluate the potential of diffusion-weighted magnetic resonance imaging (DW-MRI) as imaging biomarker for epithelial-to-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC).

Methods: In forty-two patients, preoperative apparent diffusion coefficient (ADC) values of therapy-naive PDAC were compared with immunohistochemical expression profiles of the epithelial marker E-cadherin as well as mesenchymal transcription factors Runt-related transcription factor 2 (Runx2) and Zinc finger E-box-binding homeobox 1 (Zeb1), as determined by Allred immunoreactivity score.

Results: We observed a significant positive rank correlation between the ADC and the E-cadherin Allred score (ρ = 0.553, p < 0.001) and significant negative rank correlations between the ADC and the Runx2 Allred score (ρ = -0.526, p < 0.001) as well as the Zeb1 Allred score (ρ = -0.710, p < 0.001). Compared to tumors with low ADC values < 1.3 µm2/s, tumors with ADC values ≥ 1.3 µm2/s had significantly higher Allred scores for E-cadherin (median, 4 versus 5; p < 0.001) and significantly lower Allred scores for Runx2 (median, 3 versus 2; p = 0.003) as well as Zeb1 (median, 4 versus 0; p < 0.001).

Conclusion: In PDAC, tumor plasticity in terms of EMT is well reflected by ADC values from DW-MRI. In the near future, DW-MRI could be beneficial for identification of PDAC patients that might profit from personalized EMT-targeted therapies.

Keywords: Pancreatic cancer, epithelial-to-mesenchymal transition, diffusion-weighted magnetic resonance imaging.