Test that will prevent the needless loss of the thyroid gland in people with the noncancerous condition

Mar 28 2005

New research suggests that physicians can distinguish between a type of thyroid cancer and an identical-looking, non-cancerous thyroid condition by simply determining the activity of three genes.

The findings could lead to a test that will prevent the needless loss of the thyroid gland in people with the noncancerous condition.

The study, led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, indicates that the activity levels of three genes – cyclin D2, PCSK2 (for protein convertase 2) and PLAB (prostate differentiation factor) -- might distinguish the noncancerous condition known as follicular adenoma (FA) from follicular thyroid cancer (FTC).

The findings, published online by the Journal of Clinical Endocrinology and Metabolism, also provide insight into the genetic changes that occur in those cases when FA becomes FTC.

“Presently, doctors cannot distinguish between these two conditions without surgical removal of the thyroid, even though only about 10 percent of cases prove to be cancerous,” says principal investigator Charis Eng, director of OSU’s clinical cancer genetics program. “Follicular adenoma often does not require surgery, and certainly not as extensive as for a cancer.”

“This is the first step in determining whether we can use these three genes as an objective way to tell whether a patient has cancer or simply a benign adenoma before sending that person to surgery,” says Eng, holder of the Klotz Chair in Cancer Research and a recipient of the Doris Duke Distinguished Clinical Scientist Award.

An estimated 25,690 Americans will be diagnosed with thyroid cancer this year, and an estimated 2,370 people will die of the disease. The great majority of thyroid cancers begin as thyroid nodules, which develop in about 7 percent of adult Americans (about 275,000 people in 1999).

To determine if thyroid nodules are cancerous, doctors typically withdraw cells from the nodules using a procedure known as a fine-needle aspiration biopsy. A pathologist then examines the cells to determine if they are noncancerous (benign) or cancerous.

But if the nodules consist of the thyroid’s follicular cells, Eng says, “it is often impossible to tell if they are benign or cancerous.”

So the person is sent to surgery, and the entire thyroid is often removed. Ultimately, however, only 10-20 percent of these cases are actually cancerous. The great majority of patients therefore undergo unnecessary surgery and thyroid loss.

These patients must then take synthetic thyroid-hormone tablets daily for life, with regular testing to adjust the dosage.

For this study, Eng and her colleagues used gene chip technology to compare gene activity levels in nodules from 12 patients with FA and 12 patients with FTC. The comparison included four cases of early (i.e., minimally invasive) FTCs.

Gene-chip analysis compares activity levels of tens of thousands of genes – in this case, 33,000 genes – in a sample at one time.

The researchers focused on the three genes that showed the greatest differences in activity. One gene was almost 145 times more active, a second was eight times more active and the third was 12 times less active in FTC cells compared with FA cells.

The researchers confirmed the gene-chip findings on two additional sets of tissue samples using two other measures of gene activity – a form of polymerase chain reaction (PCR) and immunohistochemistry. The validation tests showed that the three genes could distinguish FTC from FA with an accuracy of 96.7 percent.

Next, the investigators will confirm their findings using fresh thyroid follicular nodule tissue obtained by fine-needle aspiration. This work is under way.

Other OSU researchers involved in this study were Frank Weber, post-doctoral researcher in Eng’s lab; Lei Shen, assistant professor of statistics; Carl D. Morrison, assistant professor of pathology; Matthew D. Ringel, associate professor of internal medicine and co-director of the thyroid cancer unit at the James Cancer Hospital and Solove Research Institute.

Funding from the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute supported this research.

http://www.osu.edu