Liver cancer, artwork
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Molecular profiling has revealed that some liver tumors have histological features that do not easily fit either of the predominant pediatric liver cancer models—hepatoblastoma or hepatocellular carcinoma. The researchers who produced this work call these “hepatoblastomas with hepatocellular carcinoma features (HBCs).’”

The Baylor College of Medicine led team tested whether the histological features of HBCs are associated with genetic alterations, cancer-gene dysregulation, and outcomes.

“Our findings highlight the importance of molecular testing to accurately classify these tumors to optimize treatment recommendations at the time of initial diagnosis,” said Dolores López-Terrada, 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 HBCs may benefit from treatment strategies that differ from the guidelines for patients with hepatoblastoma and hepatocellular carcinoma.”

The team also report that this subtype of liver cancer is less likely to respond to chemotherapy and patient outcomes are poor. But it is hoped that this research will lead to new options for such patients.

The study was published in the Journal of Hepatology.  First author was Pavel Sumazin, associate professor of pediatrics. Both Sumazin and López-Terrada are members of the Dan L Duncan Comprehensive Cancer Center at Baylor.

Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are the predominant types of liver cancers in children. The outcomes and treatment options for these cancers differ dramatically. Most HBs have favorable outcomes following treatment by a combination of chemotherapy and resection.

Risk-stratification using a combination of clinical, histological, and molecular parameters can improve therapy selection for these patients, but it is particularly challenging for tumors with mixed HB and HCC histological features, including those in the recently created hepatocellular neoplasm not otherwise specified (HCN NOS) provisional category.

These researchers aimed to produce the first molecular characterization of clinically annotated HCN NOSs. They examined tumors’ molecular profiles, including genetic alterations and gene expression profiles. They found that the profiles did not fit into the HB or HCC molecular categories. Instead, these tumors exhibited recurring molecular features that have been observed in both HBs and HCCs. The team designated these tumors as hepatoblastomas with hepatocellular carcinoma features (HBCs).

Sumazin told Inside Precision Oncology, “We still don’t know enough about them [HBCs] as this is the first series of molecularly characterized HCN-NOS tumors reported, but our best frame of reference is hepatocellular carcinoma, a cancer that is much more often seen in adults: WNT-pathway signaling activated hepatocellular carcinoma (WNT HCC). WNT HCCs make up about 30% of adult liver cancers, but are rare in children.”

He added that, “HBCs appear to have common molecular features with these cancers and the more common pediatric liver cancer hepatoblastoma. While hepatoblastomas have few genetic mutations, HCN-NOS and HBs with overlapping histological features are more genetically unstable. They often present gains of multiple chromosomes, have mutations in multiple cancer genes, and exhibit cancer-pathway dysregulation that are not usually seen in hepatoblastoma. Interestingly, while we expected that HBCs will be diagnosed in older children, we detected some in very young patients and even babies.”

The team also examined HBC 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 HBCs and guide specialized treatment.

According to Sumazin, “This group of tumors are currently diagnosed as either hepatoblastomas or as the newly proposed provisional class of Hepatocellular Malignant Neoplasm, Not Otherwise Specified (HCN-NOS). If diagnosed as HCN-NOS, they are treated as high-risk hepatoblastomas in current clinical trials. Diagnoses are based on histological features alone.”

He added that, “We are developing and testing new therapies [for pediatric liver cancer] at Texas Children’s Hospital, and our USA and international colleagues are developing and testing new treatments, as well.’

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