New Research: Molecular profiling of pediatric thyroid cancer

Up to 30% of the time, a thyroid nodule biopsy is atypical — it’s not clear whether the nodule contains cancer.

Vivian Weiss, MD, PhD, Huiying Wang, MD, and colleagues examined results from pediatric thyroid fine needle aspiration biopsies spanning two decades at Vanderbilt and correlated the biopsy results with the histopathology of surgically removed tissue. Their study in Cancer Cytopathology, the largest of pediatric thyroid nodules to date, found that two of three “indeterminate” biopsy categories had lower rates of malignancy than previously reported.

“If a child has an atypical biopsy, they go straight to surgery, and the complication risk following surgery is higher for children than for adults,” says Weiss, assistant professor of Pathology, Microbiology and Immunology.

The trouble, Weiss notes, is that the changes in the genome that cause thyroid cancer in children are different than the molecular changes in adult thyroid cancer.

“An adult who has an atypical biopsy will get molecular testing or a follow-up biopsy, or both, but we don’t have approved molecular testing for children,” Weiss says.

Weiss and her colleagues, with collaborators at University of Pittsburgh Medical Center, have sequenced the genomes of 100 pediatric thyroid nodules — 50 benign and 50 malignant.

“Preliminarily, it looks like molecular testing may work very well for predicting malignancy in children,” Weiss says. “We are so excited about this work. With a better understanding of the molecular changes that cause thyroid cancer, we’ll be closer to providing more personalized therapy for children.”

Weiss and her group also have used surgical specimens to grow “organoids,” three-dimensional aggregates of cells that include tumor cells and other cell types that surround and support the tumor. They have grown more than 60 organoid cultures that span a range of disease, from less aggressive to highly lethal cancers, along with companion metastatic lesions. The researchers study the organoids in culture and also as xenograft tumors in animal models.

“We’re using these pediatric thyroid cancer organoids to better understand the disease, to understand what causes aggressive disease, and to look for new treatments for pediatric thyroid cancer,” Weiss says.

These resources are unique to the group at Vanderbilt.

“We’re going to make significant advances for our patients thanks to the great teamwork from our surgeons, endocrinologists and radiologists who talk to patients about the importance of research and thanks to our fantastic patients who have consented to contribute to this research,” Weiss says. “Science is better with a team.”

The V Foundation and the Children’s Cancer Research Fund provide the main funding support for this research.