TY - JOUR
T1 - Vessels encapsulating tumor clusters contribute to the intratumor heterogeneity of HCC on Gd-EOB-DTPA-enhanced MRI
AU - Matsuda, Kosuke
AU - Ueno, Akihisa
AU - Tsuzaki, Junya
AU - Kurebayashi, Yutaka
AU - Masugi, Yohei
AU - Yamazaki, Ken
AU - Tamura, Masashi
AU - Abe, Yuta
AU - Hasegawa, Yasushi
AU - Kitago, Minoru
AU - Jinzaki, Masahiro
AU - Sakamoto, Michiie
N1 - Publisher Copyright:
© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.
PY - 2024/12/11
Y1 - 2024/12/11
N2 - Background: Vessels encapsulating tumor clusters (VETC) pattern is tumor vasculature of HCC and is a predictor of prognosis and therapeutic efficacy. Recent radiological studies have demonstrated the predictability of VETC from preoperative images, but the mechanisms of image formation are not elucidated. This study aims to determine the relationship between VETC and intratumor heterogeneity in Gd-EOB-DTPA-enhanced magnetic resonance imaging (EOB-MRI) and to provide its pathological evidence. Methods: Radiologists visually classified preoperative arterial- and hepatobiliary-phase EOB-MRI images of 204 surgically resected HCCs into patterns based on heterogeneity and signal intensity; these classifications were validated using texture analysis. Single and multiplex immunohistochemistry for CD34, h-caldesmon, and OATP1B3 were performed to evaluate VETC, arterial vessel density (AVD), and OATP1B3 expression. Recurrence-free survival was assessed using the generalized Wilcoxon test. The contribution of clinicoradiological factors to the prediction of VETC was evaluated by random forest and least absolute shrinkage and selection operator regression. Results: VETC was frequently found in tumors with arterial-phase heterogeneous hyper-enhancement patterns and in tumors with hepatobiliary-phase heterogeneous hyperintense/isointense patterns (HBP-Hetero). AVD and OATP1B3 expression positively correlated with signal intensity in the arterial and hepatobiliary phases, respectively. Intratumor spatial analysis revealed that AVD and OATP1B3 expression were lower in VETC regions than in tumor regions without VETC. Patients with HBP-Hetero tumors had shorter recurrence-free survival. Machine learning models highlighted the importance of serum PIVKA-II, tumor size, and enhancement pattern of arterial and hepatobiliary phase for VETC prediction. Conclusions: VETC is associated with local reductions of both AVD and OATP1B3 expression, likely contributing to heterogeneous enhancement patterns in EOB-MRI. Evaluation of the arterial and hepatobiliary phases of EOB-MRI would enhance the predictability of VETC.
AB - Background: Vessels encapsulating tumor clusters (VETC) pattern is tumor vasculature of HCC and is a predictor of prognosis and therapeutic efficacy. Recent radiological studies have demonstrated the predictability of VETC from preoperative images, but the mechanisms of image formation are not elucidated. This study aims to determine the relationship between VETC and intratumor heterogeneity in Gd-EOB-DTPA-enhanced magnetic resonance imaging (EOB-MRI) and to provide its pathological evidence. Methods: Radiologists visually classified preoperative arterial- and hepatobiliary-phase EOB-MRI images of 204 surgically resected HCCs into patterns based on heterogeneity and signal intensity; these classifications were validated using texture analysis. Single and multiplex immunohistochemistry for CD34, h-caldesmon, and OATP1B3 were performed to evaluate VETC, arterial vessel density (AVD), and OATP1B3 expression. Recurrence-free survival was assessed using the generalized Wilcoxon test. The contribution of clinicoradiological factors to the prediction of VETC was evaluated by random forest and least absolute shrinkage and selection operator regression. Results: VETC was frequently found in tumors with arterial-phase heterogeneous hyper-enhancement patterns and in tumors with hepatobiliary-phase heterogeneous hyperintense/isointense patterns (HBP-Hetero). AVD and OATP1B3 expression positively correlated with signal intensity in the arterial and hepatobiliary phases, respectively. Intratumor spatial analysis revealed that AVD and OATP1B3 expression were lower in VETC regions than in tumor regions without VETC. Patients with HBP-Hetero tumors had shorter recurrence-free survival. Machine learning models highlighted the importance of serum PIVKA-II, tumor size, and enhancement pattern of arterial and hepatobiliary phase for VETC prediction. Conclusions: VETC is associated with local reductions of both AVD and OATP1B3 expression, likely contributing to heterogeneous enhancement patterns in EOB-MRI. Evaluation of the arterial and hepatobiliary phases of EOB-MRI would enhance the predictability of VETC.
KW - WNT/β-catenin activation
KW - arterial vessel density
KW - machine learning
KW - multiple immunofluorescence
KW - organic anion transporting peptide 1B3 (OATP1B3)
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U2 - 10.1097/HC9.0000000000000593
DO - 10.1097/HC9.0000000000000593
M3 - Article
C2 - 39670871
AN - SCOPUS:85212982388
SN - 2471-254X
VL - 9
JO - Hepatology Communications
JF - Hepatology Communications
IS - 1
ER -