TY - JOUR
T1 - Reactive Ductules Are Associated With Angiogenesis and Tumor Cell Proliferation in Pediatric Liver Cancer
AU - Lee, Sanghoon
AU - Zhou, Ping
AU - Gupta, Anita
AU - Shin, Soona
N1 - Funding Information:
Funding Supported in part by the National Institutes of Health Public Health Service Grant P30 DK078392 (Pilot and Feasibility Project and Integrative Morphology Core of the Digestive Diseases Research Core Center in Cincinnati), the Cincinnati Children’s Research Foundation and the Cincinnati Biobank, and the Better Outcomes for Children Biorepository.
Publisher Copyright:
© 2018 The Authors. Hepatology Communications published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.
PY - 2018/10
Y1 - 2018/10
N2 - While reactive ductules (RDs) have been observed in viral hepatitis, biliary atresia, nonalcoholic fatty liver disease, and adult hepatocellular carcinoma (HCC), RDs in pediatric liver cancer remain uncharacterized. This study investigated the relationship of RDs with angiogenic paracrine factors, the extent of angiogenesis, and tumor cell proliferation in pediatric hepatoblastoma (HBL)/HCC livers. We quantified the extent of RDs and their expression of paracrine factors that include vascular endothelial growth factor (VEGF), vascular endothelial growth factor D (VEGFD), platelet-derived growth factor C, and angiopoietin 1 (ANGPT1). In addition, we performed immunohistochemical detection of the endothelial marker clusters of differentiation (CD)34 and the proliferation marker Ki67 followed by correlation analyses. In HBL, we found the percentage of RDs with Ki67 expression (% Ki67+ RDs) significantly correlated with intratumoral Ki67+ areas (r = 0.5138, P = 0.0349) and % ANGPT1+ RDs positively correlated with % Ki67+ RDs (r = 0.5851, P = 0.0136). In HCC, the high ANGPT1+ RDs group (i.e., cases with % ANGPT1+ RDs ≥50) exhibited high intratumoral Ki67+ areas compared to the low ANGPT1+ RDs group. In the combined HBL and HCC liver tumor group, there was a positive association between % platelet-derived growth factor C+ RDs and intratumoral Ki67+ areas (r = 0.4712, P = 0.0099) and the high VEGFD+ RDs group (≥50%) exhibited a high number of peritumoral CD34+ vessels compared to the low VEGFD+ RDs group. Conclusion: Paracrine factor-expressing RDs are associated with angiogenesis and proliferation of pediatric liver tumors.
AB - While reactive ductules (RDs) have been observed in viral hepatitis, biliary atresia, nonalcoholic fatty liver disease, and adult hepatocellular carcinoma (HCC), RDs in pediatric liver cancer remain uncharacterized. This study investigated the relationship of RDs with angiogenic paracrine factors, the extent of angiogenesis, and tumor cell proliferation in pediatric hepatoblastoma (HBL)/HCC livers. We quantified the extent of RDs and their expression of paracrine factors that include vascular endothelial growth factor (VEGF), vascular endothelial growth factor D (VEGFD), platelet-derived growth factor C, and angiopoietin 1 (ANGPT1). In addition, we performed immunohistochemical detection of the endothelial marker clusters of differentiation (CD)34 and the proliferation marker Ki67 followed by correlation analyses. In HBL, we found the percentage of RDs with Ki67 expression (% Ki67+ RDs) significantly correlated with intratumoral Ki67+ areas (r = 0.5138, P = 0.0349) and % ANGPT1+ RDs positively correlated with % Ki67+ RDs (r = 0.5851, P = 0.0136). In HCC, the high ANGPT1+ RDs group (i.e., cases with % ANGPT1+ RDs ≥50) exhibited high intratumoral Ki67+ areas compared to the low ANGPT1+ RDs group. In the combined HBL and HCC liver tumor group, there was a positive association between % platelet-derived growth factor C+ RDs and intratumoral Ki67+ areas (r = 0.4712, P = 0.0099) and the high VEGFD+ RDs group (≥50%) exhibited a high number of peritumoral CD34+ vessels compared to the low VEGFD+ RDs group. Conclusion: Paracrine factor-expressing RDs are associated with angiogenesis and proliferation of pediatric liver tumors.
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U2 - 10.1002/hep4.1204
DO - 10.1002/hep4.1204
M3 - Article
C2 - 30288475
AN - SCOPUS:85064463626
SN - 2471-254X
VL - 2
SP - 1199
EP - 1212
JO - Hepatology Communications
JF - Hepatology Communications
IS - 10
ER -
