Gene Test May Improve Thyroid Cancer Diagnosis

By Michael Smith
ROME, 20 may 2008-- A test for the molecule galectin-3 may improve the diagnosis of thyroid cancer and reduce the number of unneeded surgeries, researchers here said.
In a prospective study of 465 patients referred for surgery, testing for the molecule identified cancerous thyroid nodules 93% of the time and benign nodules 78% of the time, according to Armando Bartolazzi, M.D., of St. Andrea Hospital here, and colleagues.
If the decision to operate had been based on the test results, only 134 thyroid operations would have been done on the 465 patients -- 71% of the surgeries would have been avoided, Dr. Bartolazzi and colleagues reported online in Lancet Oncology.
On the other hand, the researchers said, the test misclassified 29 malignant lesions as benign, so it can't entirely replace the standard diagnostic tool -- fine needle aspiration followed by histological examination for cancerous cells.
Instead, they said, it "represents a complementary diagnostic method" for nodules that are indeterminate after the histological study.
In the U.S., about 5% of the population has palpable thyroid nodules but the fine needle aspiration method is not able to distinguish clearly between benign and malignant lesions in up to 30% of cases, meaning many patients are referred to surgery without a convincing demonstration of cancer, the researchers said.
Indeed, on final histology, only between 10% and 15% of excised nodules turn out to be malignant, they said.
Galectin-3 is a member of the lectin family of molecules that is involved in several biological functions, including cell adhesion, cell-cycle regulation, apoptosis, and tumor progression.
Several lines of evidence suggest that the molecule is expressed in most thyroid tumors, but not in normal thyroid tissue, the researchers said.
To see if a test for the molecule could improve diagnosis, Dr. Bartolazzi and colleagues at 11 Italian thyroid centers prospectively studied 465 patients referred for surgery after the fine needle aspiration diagnosis was unclear.
Analysis found that:
71% of the pre-operative thyroid samples (or 331 of 465) did not express galectin-3 and 85% of those were later classified as benign at final histology.
Galectin-3 expression was found in 29% of the samples (or 134 of 465) and 75% of those were later classified as malignant.
Overall, the sensitivity of the test was 78% and the specificity was 93%. The test correctly classified 88% of the patients referred for surgery.
The estimated positive predictive value was 82% and negative predictive value was 91%.
On the other hand, 29 of 130 cancers -- or 22% -- were missed by the galectin-3 test.
The researchers said that "technical issues" might have caused some of the cancers to be missed, but a substantial fraction of the missed tumors probably did not express galectin-3, suggesting other molecular changes might be causing the disease.
On the other hand, as expected, most of the benign lesions did not express the molecule.
The study was supported by the Compagnia di San Paolo, Progetto Oncologia 2002-2006 of Turin, Italy and the Italian Association for Cancer Research.
Dr. Bartolazzi reported a translational research grant from the Italian Association for Cancer Research. Other authors declared no potential conflicts and noted that none of them benefits financially from the galectin-3 test.
Primary source: Lancet OncologySource reference:Bartolazzi A, et al "Galectin-3-expression analysis in the surgical selection of follicular thyroid nodules with indeterminate fine-needle aspiration cytology: a prospective multicentre study" Lancet Oncology 2008; DOI: 10.1016/S1470-2045(08)70132-3.