DNA analysis could boost accuracy of thyroid tests

Nov 14 2006

By fine-tuning "fine-needle aspiration" biopsies with a super-fast genetic microarray technology, a team of surgeons from NewYork-Presbyterian Hospital/Weill Cornell Medical Center in New York City says they can greatly enhance the accuracy of these tests.

"For patients with worrisome thyroid nodules, this means better information on whether the nodule is malignant or benign. That should help them and their doctors make better decisions as to what treatment they'd like to pursue," explains senior researcher Dr. Thomas J. Fahey III, associate professor of surgery and Frank Glenn Faculty Scholar in Surgery at Weill Cornell Medical College, and associate attending surgeon at NewYork-Presbyterian Hospital/Weill Cornell Medial Center in New York City.

The findings were published in a recent issue of the Journal of Molecular Diagnostics.

Since its advent in the 1970s, endocrinologists have typically used fine needle aspiration -- the nonsurgical removal of a tiny bit of tissue via needle -- as their biopsy method of choice when investigating suspicious thyroid nodules.

However, the accuracy of these tests has remained unsatisfactory because standard histological (cell-based) examination in the lab can't always distinguish cancerous or pre-cancerous tissues from samples that are benign.

"When biopsies fall into that gray area, doctors typically advocate removal of part or all of the organ," says lead researcher Dr. Carrie C. Lubitz, now a surgical resident at NewYork-Presbyterian/Weill Cornell. But organ removal means a lifetime of taking synthetic thyroid hormone, so the decision can be a tough one.

She and Dr. Fahey have long understood that malignant and benign cells have distinct genetic patterns or "signatures" that clearly delineate one from the other. Unfortunately, scientists have only been able to test tissue for one or a few genes at a time -- slowing down research and making gene-based diagnosis impractical.

"The advent of much faster "microarray" genetic analysis has changed all that," Dr. Fahey says.

The breakthrough technologies developed over the last decade mean pathologists and other experts can now comb through a cell's genome at great speed, using bits of genetic material call RNA.

"It's like speed-reading -- the difference between reading one line on a page and reading the whole book," explains Dr. Fahey.

His team has been working with this technology for the past decade, he says, "but it's only been in the past couple of years that we were able to obtain enough RNA from standard fine-needle aspirates to gather enough data for accurate microarray analysis."

In the study, the team created microarray-generated "gene expression profiles" from fine-needle aspirates by comparing the expression of thousands of genes from both cancerous and benign thyroid tissues. This process ended in a grouping of 25 differently expressed genes that helped distinguish malignant from benign growths.

"We next tested the accuracy of these patterns using 22 fine-needle aspirate samples from benign or malignant thyroid nodules," Dr. Lubitz explained.

"In all but one case, the microarray test agreed completely with the results of extensive histological analysis in the lab," she said.

According to the researchers, a move from histological to microarray analysis of thyroid aspirates could impact anywhere from 5 to 25 percent of patients undergoing this kind of diagnosis -- giving them a better grasp of whether they might require surgery, for example.

Cost remains a factor, with a single microarray screen currently totaling about $500. "We anticipate, however, that as this technology becomes more widespread and improves, the price per test will fall much lower," Dr. Fahey says.

The bottom line, according to the researchers: "Advances in gene-based diagnostics are going to make clinical decisions about thyroid and other cancers a lot less uncertain," Dr. Lubitz says.

The study was funded by the G. Thomas Shires Faculty Scholar Award.

Co-researchers include Dr. Theresa Scognamiglio, Stacy K. Ugras, Biaxin Zhu and Yao-Tseng Chen -- all of NewYork-Presbyterian Hospital/Weill Cornell Medical Center in New York City; and J. Jacob Kazam of Rutgers University, in New Brunswick, N.J.