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Three-gene profile by OSU researchers may lessen thyroid removal, spot cancer

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A small study led by Charis Eng, director of the Ohio State University clinical cancer genetics program, points to the expression levels of three genes as markers of thyroid cancer, a finding that may lead to a clinical diagnostic test that will save thousands of US patients from unnecessary thyroid removal and lifetimes of hormone maintenance.

"What we seek ... is the Holy Grail of managing thyroid nodules," Eng told Pharmacogenomics Reporter this week. "It's no secret that the whole world is looking at this — namely that thyroid nodules are very significant — it's even said that if you look at the autopsy staining of people who die at the age of 90," approximately 70 to 90 percent will have a nodule, she said.

About 7 percent of adults in the United States develop thyroid nodules, which are ordinarily sampled for evaluation by cytology through fine-needle aspiration, said Eng. But when pathologists scrutinize follicular thyroid cells — from benign follicular adenomas, "it is not possible to rule out malignancy," she said. Patients with these follicular adenomas usually undergo thyroid-removal surgery, even though only about 10 to 20 percent will develop into cancerous tissue, Eng told Pharmacogenomics Reporter.

"So our study sought a better way … that will give a high sensitivity" in distinguishing true follicular thyroid cancer from a harmless follicular adenoma, said Eng. Her research group used Affymetrix's GeneChip and U133 whole-genome microarray identify three genes whose expression was markedly different in 12 benign thyroid-nodule cell samples and 12 tumor-cell samples, then validated their results using PCR and immunohistochemistry, she said.

Ultimately, Eng and her colleagues found that the expression levels of cyclin D2, protein convertase 2, and prostate differentiation factor could distinguish tumor cells from normal cells with an accuracy of 96.7 percent, she said. "The pure science, the fundamental knowledge [gained] is that we have also found new genes that have never been implicated in thyroid cancer," said Eng.

The reliability of the three genes must first be validated in "real fine-needle aspirations" before it can be considered for use in a diagnostic, said Eng. But "this is a move toward one day making [a test] primetime for real clinical care," she said. The group had not yet spoken to any diagnostic companies with an interest in the area, she added. "If someone can take it and turn it into a diagnostic test for patients, that's great."

Tissue for follow-up studies will take "at least" two years to collect, and one year to analyze, so a diagnostic is at least three years away, said Eng.

In addition to the cost of unwanted surgery, patients who have a thyroid unnecessarily removed must pay for thyroid replacement therapy for the rest of their lives.

— CW

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