A team of researchers at Baylor College of Medicine and Texas Children’s Cancer Center in Houston, Texas, have identified a new molecular type of high-risk pediatric liver cancer.

Although the treatment options for hepatoblastoma and hepatocellular carcinoma, the predominant types of liver cancers in children, differ dramatically and most hepatoblastoma’s have favorable outcomes following treatment by a combination of chemotherapy and resection,[a] the researchers observed that the new typeof high-risk pediatric liver cancer is associated with specific molecular features both seen in hepatoblastoma and hepatocellular carcinoma, and have poor outcomes irrespective of the patient age.

Over the last 3 decades, hepatoblastoma, generally diagnosed in young children, has see the highest average annual percent increase in incidence. In contrast, hepatocellular carcinoma is more commonly seen in adolescents and young adults. Bit when diagnosed in (young) children, hepatocellular carcinoma is often associated with underlying genetic, metabolic, and inflammatory liver conditions.[1][2]

Study results
The results if the single-institution study, funded by the Cancer Prevention and Research Institute of Texas, the European Union’s Horizon 2020, the Schindler Foundation, and the National Cancer Institute, were published in the Journal of Hepatology, and showed that these tumors have better outcomes when patients were treated by transplantation, rather than by chemotherapy and surgery alone.[3]


“Until recently, nearly all pediatric liver cancers were classified as either hepatoblastoma or hepatocellular carcinoma,” said Pavel Sumazin, Ph.D, associate professor of pediatrics at Baylor College of Medicine and Texas Children’s Cancer and Hematology Center and the first author of the study.

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Pavel Sumazin, Ph.D, associate professor of pediatrics at Baylor College of Medicine and Texas Children’s Cancer and Hematology Center and the first author of the study. Sumazin is also a members of the Dan L Duncan Comprehensive Cancer Center at Baylor. Photo courtesy:© Baylor College of Medicine®. Used with permission

“However, pediatric pathologists observed that some liver tumors have histological features that do not easily fit the hepatoblastoma or hepatocellular carcinoma models. These cancers are less likely to respond to chemotherapy, and patient outcomes are poor,” Sumazin added.

No fit
The researchers examined the molecular profiles of the tumors, including genetic alterations and gene expression profiles, and they found that these profiles do not fit into the hepatoblastoma or hepatocellular carcinoma molecular categories.

Instead, the researchers noted that these tumors exhibited recurring molecular features that have been observed in both hepatoblastoma and hepatocellular carcinoma. They designated these tumors as hepatoblastomas with hepatocellular carcinoma features, which resulted in the creation of the provisional HCN NOS diagnostic category designed to identify and characterize these neoplasms.[4]

Dolores H. Lopez-Terrada, MD, Ph.D., is Chief, Division of Genomic Medicine Texas Children’s Hospital and Professor, Department of Pathology and Immunology, and Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine. Photo courtesy:© Texas Children’s Hospital. Used with permission.

More resistant
The researchers also examined hepatocellular carcinoma treatments and outcomes and found that they tended to be more resistant to standard chemotherapy and have poor outcomes when not treated with more aggressive surgical approaches, including transplantation. Based on their findings, the team proposed a diagnostic algorithm to stratify hepatocellular carcinoma and guide specialized treatment.

“Our findings highlight the importance of molecular testing to accurately classify these tumors to optimize treatment recommendations at the time of initial diagnosis ,” explained Dolores Lopez-Terrada, MD, Ph.D., corresponding author of the paper, professor of pathology, immunology and pediatrics at Baylor and chief of the division of genomic medicine at Texas Children’s.

“Our analysis suggested that children with hepatocellular carcinoma may benefit from treatment strategies that differ from the guidelines for patients with hepatoblastoma and hepatocellular carcinoma.”

Note: [a] The clinical presentations, treatment options, and outcomes for hepatoblastoma and hepatocellular carcinoma differ dramatically, with 5-year overall survival rates near 70% for hepatoblastoma and 30% for hepatocellular carcinoma patients.

[1] Hubbard AK, Spector LG, Fortuna G, Marcotte EL, Poynter JN. Trends in International Incidence of Pediatric Cancers in Children Under 5 Years of Age: 1988-2012. JNCI Cancer Spectr. 2019 Mar;3(1):pkz007. doi: 10.1093/jncics/pkz007. Epub 2019 Apr 9. PMID: 30984908; PMCID: PMC6455426.
[2] Czauderna P, Lopez-Terrada D, Hiyama E, Häberle B, Malogolowkin MH, Meyers RL. Hepatoblastoma state of the art: pathology, genetics, risk stratification, and chemotherapy. Curr Opin Pediatr. 2014 Feb;26(1):19-28. doi: 10.1097/MOP.0000000000000046. PMID: 24322718.
[3] Sumazin P, Peters TL, Sarabia SF, Kim HR, Urbicain M, Hollingsworth EF, Alvarez KR, Perez CR, Pozza A, Panah MJN, Epps JL, Scorsone K, Zorman B, Katzenstein H, O’Neill AF, Meyers R, Tiao G, Geller J, Ranganathan S, Rangaswami AA, Woodfield SE, Goss JA, Vasudevan SA, Heczey A, Roy A, Fisher KE, Alaggio R, Patel KR, Finegold MJ, López-Terrada DH. Hepatoblastomas with carcinoma features represent a biological spectrum of aggressive neoplasms in children and young adults. J Hepatol. 2022 May 13:S0168-8278(22)00275-6. doi: 10.1016/j.jhep.2022.04.035. Epub ahead of print. PMID: 35577029.
[4] López-Terrada D, Alaggio R, de Dávila MT, Czauderna P, Hiyama E, Katzenstein H, Leuschner I, Malogolowkin M, Meyers R, Ranganathan S, Tanaka Y, Tomlinson G, Fabrè M, Zimmermann A, Finegold MJ; Children’s Oncology Group Liver Tumor Committee. Towards an international pediatric liver tumor consensus classification: proceedings of the Los Angeles COG liver tumors symposium. Mod Pathol. 2014 Mar;27(3):472-91. doi: 10.1038/modpathol.2013.80. Epub 2013 Sep 6. PMID: 24008558.

Featured image: National Cancer Institute on Unsplash Used with permission.


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