Notable Publication from the UPMC Division of Endocrinology and Metabolism

April 10, 2023

UPMC Division of Endocrinology and Metabolism faculty recently published a notable research article in the journal Surgery that explored the association of molecular testing with tumor phenotype in thyroid cancer.

Publication Information

Liu JB, Ramonell KM, Carty SE, McCoy KL, Schaitkin BM, Karslioglu-French E, Morariu EM, Ohori PN, Seethala RR, Chiosea SI, Nikiforova MN, Nikiforov YE, Yip L. Association of Comprehensive Thyroid Cancer Molecular Profiling with Tumor Phenotype and Cancer-specific Outcomes. Surgery. October 2022.

Background: Molecular testing improves the diagnostic accuracy of thyroid cancer. The purpose of this study was to assess whether specific molecular testing results are associated with tumor phenotype or provide prognostic information.

Methods: Consecutive thyroid cancer patients after index thyroidectomy with ThyroSeq version 3 (Rye Brook, NY) molecular testing obtained on preoperative fine-needle aspiration or thyroidectomy specimens from patients with thyroid cancer were categorized into three molecular risk groups based on detected mutations, fusions, copy number alterations, and/or gene expression alterations and correlated with histopathology and recurrence, defined as biochemical or structural.

Results: Of 578 patients, 49.9%, 37.5%, and 12.6% had molecular risk group –low, molecular risk group–intermediate, and molecular risk group–high cancers, respectively. With a median 19-month follow-up, 9.1% patients recurred. Compared with molecular risk group–low, molecular risk group–intermediate cancers were diagnosed in younger patients and more often had microscopic extrathyroidal extension, involved margins, and nodal disease. Compared with molecular risk group–intermediate, molecular risk group–high cancers were diagnosed in older patients and more often had gross extrathyroidal extension and vascular invasion. In a multivariable analysis, recurrence was more likely in molecular risk group–high cancers than in molecular risk group–intermediate (hazard ratio = 4.0; 95% confidence interval, 1.9–8.6; P < .001) and more likely in molecular risk group–intermediate than in molecular risk group–low (hazard ratio = 5.0; 95% confidence interval, 2.0–12.5; P < .001).

Conclusion: Using modern comprehensive genotyping, the genetic profile of thyroid cancers can be categorized into three novel molecular risk groups that were associated with histopathologic phenotype and recurrence in short-term follow-up.