Study of WNT and NOTCH Signaling Pathways in Hepatoblastoma: Role in Diagnosis and Prognosis.

Abstract

Background. Hepatoblastoma has an aggressive course in a subset of children. Studying various markers related to the signaling pathways can aid in understanding its pathogenesis at the molecular level and may pave the way for targeted therapy. We conducted this study to evaluate the immunohistochemical expression of markers related to WNT and NOTCH signaling pathways in hepatoblastoma and to compare them among its histological subtypes. Methods. The specimens of hepatoblastoma diagnosed over a period of 8 years were retrieved. Clinicoradiological data was obtained. Slides were reviewed and detailed histopathological parameters, diagnosis, and subtypes were reevaluated. Immunohistochemistry for β-catenin, CCND1, glutamine synthetase, MYC, AXIN2, NOTCH2, DLK1, and HES1 was performed. Statistical analysis was done. Results. A total of 51 samples of hepatoblastoma were included in the study. Mixed epithelial-mesenchymal hepatoblastoma was the most common histologic subtype. PRETEXT IV, high-risk group, high mitotic index, and less differentiated histologic subtype were associated with worse outcomes. β-catenin, AXIN2, CCND1, expression was more in less differentiated subtypes. MYC, HES1, and glutamine synthetase expression was more common in the fetal component. NOTCH2 and DLK1 expression was seen across all types. A statistically significant association was observed among AXIN2 expression with β-catenin, CCND1, and MYC nuclear expression. Mean overall survival was 66.6 months and mean event-free survival was 54.7 months. Conclusions. The NOTCH pathway converges with the WNT pathway. Differential expression of the immunohistochemical markers of these pathways helps in the semiquantitation of various epithelial components, guides adjuvant treatment, and patient prognostication.