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May 23, 2008 — Testing thyroid nodules for the presence of
galectin-3 might reduce the number of unnecessary surgeries for potential
thyroid cancer, researchers report in a paper published online May 19 in Lancet
Oncology. Although the galectin-3 test will not replace conventional
fine-needle-aspiration (FNA) cytology, it can be a complementary diagnostic
method for indeterminate follicular nodules.
"Our study is the first prospective multicenter study in which the
galectin-3 thyrotest has been used preoperatively to characterize follicular
thyroid proliferations that remain indeterminate at FNA cytology," said lead
author Armando Bartolazzi, MD, PhD, from the department of pathology at St.
Andrea University Hospital, in Rome, Italy. "This study shows the real
clinical impact of this test method in the management of thyroid
lesions."
FNA is the standard method of evaluating thyroid lesions, but it is unable
to distinguish between benign and malignant disease in about 15% to 30% of
the tests performed. As a result, a large number of patients are
unnecessarily referred for thyroidectomy, and final histologic testing often
confirms malignancy in only about 10% to 15% of excised lesions.
"Our current results show that when galectin-3 expression is correctly
evaluated on follicular thyroid nodules indeterminate at FNA cytology, it [is
useful in] distinguishing benign from malignant thyroid lesions," Dr.
Bartolazzi told Medscape Oncology. "This strategy can potentially
prevent about 70% of unnecessary thyroid surgical procedures, and it
represents a big achievement, considering the fact that most of these thyroid
proliferations are benign."
Galectin-3 is a beta-galactoside-binding protein that regulates many
biologic processes, including cell adhesion, migration, cell growth, tumor
progression, metastasis, and apoptosis. Dr. Bartolazzi pointed out that the
biologic rationale for galectin-3 expression in transformed thyroid cells has
been extensively reported in the literature and, in an international
multicenter trial, was evaluated retrospectively on a large number of benign
and malignant thyroid lesions postoperatively.
"That study provided the basis for the use of galectin-3 in the
preoperative characterization of thyroid nodules on FNA-derived cell blocks,"
he said. "The galectin-3 test does not represent a panacea, but it should be
integrated into a careful clinical and pathologic evaluation of each specific
thyroid lesion."
In this prospective study, Dr. Bartolazzi and colleagues evaluated the
ability of galectin-3 expression to distinguish preoperative benign and
malignant follicular thyroid nodules when FNA findings were unclear. In
collaboration with 11 specialized thyroid institutions, final histologic
diagnoses were compared with the preoperative diagnostic findings of
galectin-3 expression analyses in 465 patients who were referred for thyroid
surgery.
Their results showed that galectin-3 expression was absent in 331
(71%) of the 465 thyroid nodules that were assessed preoperatively and,
of these, 280 (85%) were diagnosed as benign at final histology.
Conversely, 29 (9%) of these nodules were subsequently diagnosed as
malignant, indicating potential false negatives. Of this group of 29
false-negative lesions, 8 (28%) showed variable galectin-3 expression
when testing was performed postoperatively. The authors note that the
changes in results suggest technical problems in the FNA sampling or
the test itself.
The expression of galectin-3 was observed preoperatively in 134 (29%)
thyroid samples; of this group, 101 (75%) were confirmed as malignant. In 22
patients, however, galectin-3-positive nodules were initially categorized as
benign, but half of them had nodules that were ultimately classified as
borderline lesions.
Overall, the results show that 381 (88%) of 432 patients who were
eventually referred for thyroidectomy were correctly classified
preoperatively by the galectin-3 test. Therefore, the authors surmise, many
unnecessary thyroid operations could be avoided. The overall sensitivity of
the test was 78%, the specificity was 93%, the estimated positive-predictive
value was 82%, and the negative-predictive value was 91%. However, 29 of 130
cancers (22%) were missed by the galectin-3 test; the authors attribute
technical issues to at least some of these diagnostic failures. This could be
remedied with more specific training and dedicated workshops on the use of
galectin-3 expression testing.
Technical issues aside, the authors note that at least 21 (16%) of the
130 thyroid carcinomas that were analyzed failed to express galectin-3, and
they believe that it is probably due to additional molecular alterations that
affect LGALS3 gene transcription. This hypothesis is currently being
studied.
"We propose the use of galectin-3-expression analysis during the
preoperative evaluation of all thyroid nodules that remain indeterminate at
FNA cytology," he said. "The test requires formalin-fixed and
paraffin-embedded cellblocks and should be performed by an experienced
cytologist or pathologist. A good quality FNA of the thyroid nodule is
imperative to obtain a sufficient number of thyroid cells for
galectin-3-expression analysis."
The study was funded by the Compagnia di San Paolo, Progetto Oncologia
2002-2006, and the Italian Association for Cancer Research. Dr. Bartolazzi has received a translational research grant from the
Italian Association for Cancer Research. The other authors disclosed no
relevant financial relationships, and none of them have benefited financially
from the galectin-3 test.
Lancet Oncol. Published online before print May 19, 2008.
http://www.medscape.com/viewarticle/574979?sssdmh=dm1.353973&src=nldne
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