TY - JOUR
T1 - Volumetric imaging
T2 - a potential tool to stage upper tract urothelial carcinoma
AU - Grahn, Alexandra
AU - Tanaka, Nobuyuki
AU - Uhlén, Per
AU - Brehmer, Marianne
N1 - Funding Information:
Funding This study was supported by the Foundation in Memory of Johanna Hagstrand and Sigfrid Linnér (Stiftelsen Johanna Hagstrand och Sigfrid Linnérs Minne) (AG, MB), Research and Development Grants from Karolinska University Hospital, Division of Urology, Stockholm, Sweden (AG), the Swedish Research Council (Grant no. 2017-00815 to PU), the Swedish Cancer Society (Grant no. CAN 2016-801 to PU), the Swedish Childhood Cancer Fund (Grant no. PR2018-0123 to PU), and the Olle Engkvist foundation (PU).
Funding Information:
The authors would like to thank G Jaremko, Department of Clinical Pathology and Cytology, Karolinska University Hospital Solna, Stockholm, Sweden for kindly aiding sample selection.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Purpose: To investigate whether volumetric imaging of tumor vasculature can be used to phenotypically characterize advanced upper tract urothelial carcinoma, and if this technique can distinguish aggressive invasive tumors from non-aggressive superficial ones. Methods: In a pilot study, two TaG1 and two T3G3 formalin-fixed paraffin-embedded (FFPE) tumor samples were examined using the DIPCO pipeline (Tanaka et al. in Nature Biomed Eng 1(10):796–806. https://doi.org/10.1038/s41551-017-0139-0, 2017). Briefly, punch biopsies of FFPE tumors were deparaffinized, cleared, immunolabeled with the vessel marker CD34 and imaged with a light-sheet microscope. Thereafter, the three-dimensional (3D) vasculature of the tumors was analyzed and characterized using a specialized image processing software. Results: We found that T3G3 tumors had increased CD34 density kurtosis and skewness compared to TaG1 tumors. This suggests that analysis of the 3D vasculature can distinguish between high-grade invasive and low-grade superficial tumors. Conclusions: Volumetric imaging of tumor samples may represent novel methodology that can complement conventional histopathology. Volumetric imaging enabled us to differentiate between invasive and non-invasive upper tract urothelial carcinoma. The method is of particular interest in diagnostic work-up of patients with upper tract urothelial carcinoma as previous findings indicate that volumetric imaging of vascular patterns could be used to differentiate superficial and invasive urothelial carcinoma, irrespective of if the tumor sample was deep or superficial. However, further and more extensive studies are required before this method can be applied clinically.
AB - Purpose: To investigate whether volumetric imaging of tumor vasculature can be used to phenotypically characterize advanced upper tract urothelial carcinoma, and if this technique can distinguish aggressive invasive tumors from non-aggressive superficial ones. Methods: In a pilot study, two TaG1 and two T3G3 formalin-fixed paraffin-embedded (FFPE) tumor samples were examined using the DIPCO pipeline (Tanaka et al. in Nature Biomed Eng 1(10):796–806. https://doi.org/10.1038/s41551-017-0139-0, 2017). Briefly, punch biopsies of FFPE tumors were deparaffinized, cleared, immunolabeled with the vessel marker CD34 and imaged with a light-sheet microscope. Thereafter, the three-dimensional (3D) vasculature of the tumors was analyzed and characterized using a specialized image processing software. Results: We found that T3G3 tumors had increased CD34 density kurtosis and skewness compared to TaG1 tumors. This suggests that analysis of the 3D vasculature can distinguish between high-grade invasive and low-grade superficial tumors. Conclusions: Volumetric imaging of tumor samples may represent novel methodology that can complement conventional histopathology. Volumetric imaging enabled us to differentiate between invasive and non-invasive upper tract urothelial carcinoma. The method is of particular interest in diagnostic work-up of patients with upper tract urothelial carcinoma as previous findings indicate that volumetric imaging of vascular patterns could be used to differentiate superficial and invasive urothelial carcinoma, irrespective of if the tumor sample was deep or superficial. However, further and more extensive studies are required before this method can be applied clinically.
KW - Diagnostic accuracy
KW - Prognostic tumor marker
KW - Three-dimensional imaging
KW - Tumor heterogeneity
KW - Urothelial carcinoma
KW - Volumetric imaging
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U2 - 10.1007/s00345-019-02682-1
DO - 10.1007/s00345-019-02682-1
M3 - Article
C2 - 30820651
AN - SCOPUS:85062621870
VL - 37
SP - 2297
EP - 2302
JO - World Journal of Urology
JF - World Journal of Urology
SN - 0724-4983
IS - 11
ER -