Abstract A022: Role of imaging mass cytometry in studying hepatoblastoma vascular invasion

Abstract

Abstract Introduction: Hepatoblastoma (HB) is the most common liver cancer in children with a survival rate of less than 50% in patients with high-risk disease, especially those with vascular invasion (VI). Patients with VI receive aggressive therapies that are toxic and ineffective; therefore, a better understanding of the biomarkers and biology of VI in HB is urgently needed. Methods: Using imaging mass cytometry (IMC) we analyzed 18 pre-validated protein targets on two of our formalin-fixed paraffin embedded (FFPE) HB patient samples; one with VI and one without VI. For confirmation of the proteins of interest, we performed immunohistochemistry (IHC) on primary and metastatic lesions from a separate patient. We performed RNA sequencing of one of our primary liver tumor and two sub-clones of that tumor, one inside an intrahepatic vessel and one sample representing tumor vessel thrombus. Results: By IMC, we found that protein expression of c-Myc and YAP-1 are increased in the areas of VI as the tumor invades the neighboring blood vessel. YAP-1 and c-Myc expression were low in the patient without VI. When examining the IHC of the separate patient with metastatic lung disease, we noted clear nuclear positivity of YAP-1 and c-Myc in the metastatic cells, compared to the negative nature of the primary liver tumor. Our RNA sequencing data showed that the average gene expression of c-Myc of the tumor in intrahepatic vessel and tumor vessel thrombus was 1.61 times higher than the primary tumor. The tumor found in the intrahepatic vessel and tumor vessel was found to have 1.29 times higher expression of Yap-1 compared to the primary tumor. Conclusions: YAP-1 and c-Myc had higher expression in hepatoblastoma as the tumor cells progress to invade the vasculature and metastasize. YAP-1 and c-Myc expression appears to play a role in vascular invasion that is maintained when tumors grow in the metastatic sites. Citation Format: Andres F. Espinoza, Roma Patel, Sarah Woodfield, Sanjeev A. Vasudevan. Role of imaging mass cytometry in studying hepatoblastoma vascular invasion [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr A022.