Molecular Testing Enhances Thyroid FNA Sample Analysis

Paul W. Mamula, PhD

May 17, 2010

May 17, 2010 (Minneapolis, Minnesota) — Molecular testing can aid in the diagnosis of heterogeneous unclassified thyroid cancer, according to a series of studies presented here at the American Thyroid Association (ATA) Spring 2010 Meeting.

Yuri E. Nikiforov, MD, PhD, professor of pathology at the University of Pittsburgh Medical Center and director of the Division of Molecular Anatomic Pathology in Pennsylvania, presented the latest findings from molecular diagnostic testing with fine-needle aspiration (FNA) samples taken from patients with thyroid cancer of indeterminate cytology.

Dr. Nikiforov noted that the problem for patients with indeterminate cytology is avoiding unnecessary surgery. For those who have had surgery, the goal is reducing the potential for suboptimal therapy that can lead to cancer recurrence.

Molecular diagnostic testing is valuable for such patients because the molecular diagnostic markers, if present, are uniformly present in tissue, Dr. Nikiforov told meeting attendees.

Individual markers for particular genes can identify a malignancy when cytology is indeterminate, but individual markers cannot detect all tumors, he pointed out.

Dr. Nikiforov presented findings from one of his ongoing studies, based on data collected from 117 nodules with follicular lesions of indeterminate cytology that were accessible for molecular analysis. This is the lowest cytological risk group, he noted.

His group has identified 27 thyroid cancers on surgical pathology. Molecular testing was able to identify 60% (12 of 20) of the malignancies.

If a mutation is identified, there is more than a 90% chance that the patient will have a malignant tumor, Dr. Nikiforov said. When patients lack the mutation, risk drops to 5% to 8%. However, the test cannot currently completely rule out the risk for cancer in the indeterminate cells, he noted.

The Revised ATA Management Guidelines for Patients With Thyroid Nodules and Differentiated Thyroid Cancer recommend that the use of molecular markers (e.g., BRAF, RAS, RET/PTC, Pax8-PPARgamma, or galectin-3) be considered for patients with indeterminate cytology on FNA, Dr. Nikiforov pointed out (Thyroid. 2009;19:1167-1214).

Dr. Nikiforov described the procedure used at his institution for diagnosis. After FNA, smears are made. A small amount of the remaining material is washed and sent for molecular diagnosis; the rest of the sample is saved.

The cytologist analyzes the smears, and if the diagnosis is BRAF-negative, nothing else is done. Dr. Nikiforov stated that some studies suggest that these samples might benefit from additional molecular marker testing, but his institution does not believe that further testing of these samples is cost effective.

If cytology is indeterminate or positive, the vial is retrieved and tested for additional molecular alterations. Patients found to be positive for mutations are strongly encouraged to have surgery, using BRAF-status as a guide.

Dr. Nikiforov noted that such a protocol can only be done in close collaboration with clinicians, including endocrinologists and endocrine surgeons. Joint discussions about all clinical factors, including nodule ultrasound imaging, tumor dimensions, and cytology, can be used to determine the best options for patients.

Dr. Dr. Mingzhao Xing, MD, PhD, associate professor at Johns Hopkins University in Baltimore, Maryland, an expert on the BRAF mutation who moderated the session moderator, told Medscape Diabetes and Endocrinology that the only downside to using individual markers is sensitivity. He noted that because not all tumors have a particular marker, the ATA guidelines suggest using additional markers.

Dr. James Fagin, MD, chief of the endocrine service at Memorial Sloan-Kettering Cancer Center in New York City, said that the use of molecular methods and markers have become fairly common at his institution. He added that they refine the ability to do preoperative diagnosis and to make treatment decisions.

All of the study reviews presented at this meeting will appear in the July 2010 issue of Thyroid.

Dr. Nikiforov reports receiving research support from National Institutes of Health (NIH) grants, but has disclosed no relevant financial relationships. Dr. Xing reports receiving royalties as the coholder of a licensed patent for BRAF mutation in thyroid cancer. Dr. Fagin reports receiving grant support NIH.

American Thyroid Association (ATA) Spring 2010 Meeting. Presented May 14, 2010.

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