Molecular knowledge explains response in differentiated thyroid cancer

CHICAGO — Molecular abnormalities in radioactive iodine-refractory differentiated thyroid cancer can vary between the primary tumor and metastatic site, according to results of a pilot study presented at the Annual Meeting of the American Thyroid Association.

This heterogeneity may explain altered responses to therapeutic intervention, the authors concluded.

“Management of metastatic radioactive iodine-refractory differentiated thyroid cancer is a therapeutic challenge,” Cristiane J. Gomes-Lima, MD, researcher at MedStar Health Research Institute in Washington D.C., said during the presentation. “There is a growing body of knowledge on the genetic hallmarks of thyroid cancer, however, little is known about the matched molecular profile of the primary tumor and the metastases, and if they harbor the same genetic abnormalities.”

Gomes-Lima and colleagues sought to compare the molecular profiles of paired tumor specimens from 12 patients (median age, 61 years; range, 25-82) with metastatic radioactive iodine-refractory differentiated thyroid cancer. Nine had papillary thyroid cancer, two had Hürthle cell thyroid cancer and one had follicular thyroid cancer.

Ten of the patients were men. Mean tumor size was 3.9 cm ± 2.2 cm.

Researchers genotyped tissue from primary tumor and metastatic sites.

They used a panel of 592 genes from Caris Life Sciences to perform next-generation sequencing, RNA sequencing and immunohistochemistry.

“A bioinformatic analysis was performed using a structural and functional annotation pipeline mapped to regulatory pathways related to thyroid physiology,” Gomes-Lima and colleagues wrote.

Researchers observed distant metastases in the lungs (n = 10), bones (n = 4) and liver (n = 1).

Evaluation of the genetic landscape of the paired sites revealed alterations in BRAF, NRAS, HRAS, TP53, ATM, MUTYH, POLE and NTRK genes, including BRAF and NTRK fusions.

BRAF V600E mutation was the most common point mutation observed in the paired specimens (41.6%; n = 5).

Driver mutations appeared consistent between sites; however, researchers observed some discordance among three patients for other point mutations.

PD-L1 expression at metastatic sites was highly positive (95%) for one patient but negative for the other 11 patients.

“Molecular abnormalities in the primary tumor and metastatic sites of differentiated thyroid cancer show heterogeneity,” Gomes-Lima said. “Mutational changes between primary and metastatic tumor may explain altered responses to therapeutic intervention. A better understanding of the genetic and biologic aspects of metastatic differentiated thyroid cancer will allow for the development of more effective targeted therapies.” – by Jennifer Southall

Reference:

Gomes-Lima CJ, et al. Highlighted Oral Abstract 5. Presented at: Annual Meeting of the American Thyroid Association; Oct. 30-Nov. 3, 2019; Chicago.

Disclosures: Gomes-Lima reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.