Yuri E. Nikiforov, MD, PhD
A new test has been developed to identify the difference between malignant and benign nodules in the thyroid gland, which could potentially reduce the number of unnecessary surgeries, according to an announcement from The University of Pittsburgh Schools of the Health Sciences.
The Next Generation Sequencing test, known as ThyroSeq, is a custom panel designed to target 12 cancer genes with 284 mutational hot spots. The test made its debut at UPMC/UPCI Multidisciplinary Thyroid Center at the University of Pittsburgh in October.
The test, which requires a small amount of DNA and can be performed in a variety of thyroid tissue and fine-needle aspiration samples, allows pathologists to simultaneously check for multiple genetic markers by collecting just a few cells instead of using an ultrasound-guided biopsy on the patient.
“The test we had been using can distinguish between cancerous and benign nodules about 70 percent of the time, but that means the result is uncertain in nearly a third of cases,” Yuri Nikiforov, MD, PhD, director of thyroid molecular diagnostics at the thyroid center and a professor of pathology at the University of Pittsburgh School of Medicine, said in a news release. “When that happens, the patient has to have the nodule surgically removed so that more extensive testing can be done. If it turns out to be cancerous, yet another operation might be needed to remove the entire thyroid gland.”
The growth of a small mass or nodule of the thyroid gland is common, especially with aging, Nikiforov said in a statement. Approximately 100,000 thyroid nodule biopsies are done annually and most of these patients must undergo follow-up testing and diagnostic surgery, even though the nodules are benign 90% of the time.
ThyroSeq detected point mutations in 30%–83% of specific types of thyroid cancer, according to a study by a team at the University of Pittsburgh.
The study also demonstrated that the ThyroSeq DNA assay identified mutations in 19 of 27 of classic papillary thyroid carcinomas (PTCs) (70%), 25 of 30 follicular variant PTCs (83%), 14 of 18 conventional (78%) and 7 of 18 oncocytic follicular carcinomas (39%), 3 of 10 poorly differentiated carcinomas (30%), 20 of 27 anaplastic (ATCs) (74%), and 11 of 15 medullary thyroid carcinomas (73%). In contrast, 5 of 83 benign nodules (6%) were positive for mutations. Most tumors had a single mutation, whereas several ATCs and PTCs demonstrated two or three mutations.
The most common mutations detected were BRAF
followed by PIK3CA
, TP53, TSHR, PTEN, GNAS, CTNNB1
, and RET
. The BRAF
mutant allele frequency was 18%–48% in PTCs and was lower in ATCs.
“The ultimate goal of molecular testing is to allow patients to have the initial definitive operation for thyroid cancer and to avoid diagnostic surgery for benign conditions,” Multidisciplinary Thyroid Center co-director Sally E. Carty, MD, said in a news release “The next -generation sequencing test is very exciting, innovative and promising because it’s designed to pick up a much higher percentage of cancers.”
According to University of Pittsburgh researchers, data collected from ThyroSeq suggest that certain gene alteration patterns may be associated with more aggressive cancers. These findings could help develop personalized treatment approaches for specific kinds of tumors.
“If we can distinguish aggressive thyroid cancers from cancers that are growing much more slowly and will not metastasize, we might be able to avoid surgery in these low-risk patients in favor of watchful waiting,” Multidisciplinary Thyroid Center co-director Steven Hodak, MD, said in a news release. “That's really the Holy Grail – finding patients both with and without thyroid cancer for whom surgery is unnecessary and not putting them through the expense and risk of surgeries they don't need.”