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The Journal of Clinical Endocrinology & Metabolism 88(2):950 –951 Copyright © 2003 by The Endocrine Society doi: 10.1210/jc.2002-021593
LETTERS TO THE EDITOR Methodological Considerations Regarding the Use of Galectin-3 Expression Analysis in Preoperative Evaluation of Thyroid Nodules To the editor:
Armando Bartolazzi, Mauro Papotti, and Fabio Orlandi Department of Pathology, St. Andrea Hospital (A.B.), University La Sapienza, Rome, Italy; and Departments of Pathology (M.P.) and Clinical and Biological Sciences (F.O.), University of Turin, Turin, Italy
Preoperative characterization of thyroid nodules by using galectin-3 immunodetection on cytological smears from thyroid FNA is going to become a widely accepted diagnostic procedure in a large number of European institutions and university hospitals. As coauthors of the multicenter study in which this test-method has been proposed and validated (1), we are obliged to comment on the article entitled “Galectin-3 is not an universal marker of malignancy in thyroid nodular disease in children and adolescents” by M. Niedziela and colleagues, published in the September issue of JCEM (2). To improve the conventional cytological evaluation of thyroid nodules, Niedziela and colleagues propose a RT-PCR-based technique instead of an immunocytochemical method. There are at least two important criticisms to this approach that need to be considered and discussed. First, it should be stressed that analysis of galectin-3 expression in thyrocytes cannot be considered as a substitute for the conventional morphological evaluation of each specific lesion. For this reason, an immunocytochemical diagnostic approach to the preoperative characterization of thyroid nodules is mandatory, because this simple and cheap procedure combines a morphological and immunophenotypical evaluation of thyroid cells. This strategy is crucial because expression of galectin-3 is normally observed in activated endothelial cells as well as in the so-called “foamy macrophages,” which are commonly observed in different benign (i.e. colloid goitres, Hashimoto’s thyroiditis, etc.) and malignant thyroid conditions. Moreover, it should be also considered that only the cytoplasm expression of galectin-3 is suggestive of malignancy, because nuclear immunoreactivity is physiologically observed in some benign thyroid conditions (3). Consequently, the use of RT-PCR for evaluation of galectin-3 expression on morphologically undefined cytological material, as Niedziela and co-authors propose, doesn’t represent a reliable diagnostic method and is affected by a large number of false positive results. With this in mind, we are not surprised about the reported results regarding galectin-3 expression in Hashimoto’s thyroiditis and other benign thyroid lesions (2). For the reason discussed above we strongly discourage the use of RT-PCR for this specific diagnostic purpose. A reliable use of RT-PCR for characterization of thyroid nodules requires the set-up of expensive and time consuming tissue micro-dissection procedures to be applied on cytological and histological preparations. Regarding the second point of discussion, expression of galectin-3 in some Hashimoto’s thyroiditis has been previously described in a very limited number of cases (1). Although the number of galectin-3 positive Hashimoto’s thyroiditis decreased consistently when a purified monoclonal antibody to galectin-3 and a biotin-free detection system were used in immunocytohistochemistry (4), we confirm the possibility that some of these thyroid diseases may express galectin-3. The significance of galectin-3 expression in focal areas of oncocytic changes observed in some Hashimoto thyroiditis is currently under investigation (paper in preparation), but the conclusion of Niedziela and colleagues that an “abundant number of oxyphilic cells in this disorder is a consequence of neoplastic transformation within Hashimoto’s goiters” appears quite imprudent, especially if this conclusion is not supported by an adequate morphological study of these intriguing lesions.
We are grateful to Professor Bartolazzi and his co-workers for their comments on our paper and will attempt to answer their pertinent queries. First, it was their previously published papers (1–3) that led us to investigate galectin-3 expression in our series of children with thyroid nodules. The aim of our study was to determine whether galectin-3 expression using the RT-PCR-based technique would improve the accuracy of preoperative diagnosis of thyroid carcinomas, because the results of fine-needle aspiration biopsies are not infallible. We reported positive expression in proliferative forms of autoimmune thyroiditis and Hashimoto thyroiditis coexisting with a follicular adenoma (4). They say that these may be false-positive RT-PCR results. The two important criticisms contained in the letter were, in our opinion, covered in our paper. First, we stated that the aim of our galectin-3 expression analysis was “to improve the classical cytological evaluation of the material obtained with ultrasound-guided biopsy,” but importantly added that this technique was not the only diagnostic approach to be employed. Secondly, they wonder whether some of the cells in the biopsy material are target cells for galectin-3 and, therefore, that false-positive results are possible in such cases. We disagree with their statement that our examination of galectin-3 expression was performed on “morphologically undefined cytological material” because we included a description of the representative cytological material obtained from biopsy, as shown in Table 1 of our paper (4). Our data concerning galectin-3 expression in Hashimoto thyroiditis, based on the RT-PCR method, are in agreement with Herrmann et al. (5) who showed that “galectin-3 was also expressed focally and weakly in reactive follicular epithelium and entrapped follicles in chronic lymphocytic thyroidits.” This paper was published precisely at the time our manuscript was being reviewed by JCEM experts. There are, however, a number of published papers supporting the possible false-positive expression of galectin-3, including those of Herrmann et al. (5) and of
Received October 14, 2002. Address correspondence to: Armando Bartolazzi, M.D., Ph.D., Department of Pathology, St. Andrea Hospital, University La Sapienza, Via di Grottarossa 1035, 00189, Rome Italy. E-mail:
[email protected].
Received November 1, 2002. Address correspondence to: Marek Niedziela, Department of Pediatric Endocrinology and Diabetes, Institute of Pediatrics, Karol Marcinkowski University of Medical Sciences in Poznan, Szpitalna Street 27/33, 60-572 Poznan, Poland.
References 1. Bartolazzi A, Gasbarri A, Papotti M, Bussolati G, Lucante T, Khan A, Inohara H, Marandino F, Orlandi F, Nardi F, Vecchione A, Tecce R, Larsson O, and the Thyroid Cancer Study Group 2001 Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions. Lancet 357:1644 –1650 2. Niedziela M, Maceluch J, Korman E 2002 Galectin-3 is not an universal marker of malignancy in thyroid nodular disease in children and adolescent. J Clin Endocrinol Metab 87:4411– 4415 3. Orlandi F, Saggiorato E, Pivano G, Puligheddu B, Termine A, Cappia S, De Giuli P, Angeli A 1998 Galectin-3 is a presurgical marker of human thyroid carcinoma. Cancer Res 58:3015–3020 4. Herrmann ME, LiVolsi VA, Pasha TL, Roberts SA, Wojcik EM, Baloch ZW 2002 Immunohistochemical expression of galectin-3 in benign and malignant thyroid lesions. Arch Pathol Lab Med 126:710 –713
Authors’ Response: Methodological Considerations Regarding the Use of Galectin-3 Expression Analysis in Preoperative Evaluation of Thyroid Nodules To the editor:
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Letters to the Editor
Beesley and McLaren (6), which are based on immunohistochemical analysis as well as those of Bernet et al. (7) and Martins et al. (8), based on the RT-PCR technique. We therefore postulate that both RT-PCR and immunocytochemical diagnostic approaches performed preoperatively and RT-PCR and immunohistochemical analysis performed postoperatively on the same specimen would help in the phenotyping of target cells for galectin-3 and thereby answer the question as to whether a straight correlation exists between the two methods or not. Finally, our paper does not disagree with their previously published findings (1–3) and even supports their usefulness in the preoperative detection of thyroid carcinoma. On the other hand, our paper may indicate some limitations in cases with pathogenetic and clinical diversity, such as Hashimoto thyroiditis and a solitary nodule. We want to stress that the preoperative expression of galectin-3 must be interpreted in such cases with great caution and only in parallel with routine conventional cytology, thereby improving it as a diagnostic or prognostic adjunct. Marek Niedziela, Eugeniusz Korman, and Jarosław Maceluch Department of Pediatric Endocrinology and Diabetes, Institute of Pediatrics (M.N., E.K.), Karol Marcinkowski University of Medical Sciences in Poznan, 60-572 Poznan, Poland; and Department of Gene Expression, Institute of Molecular Biology and Biotechnology (J.M.), University of Adam Mickiewicz, 60572 Poznan, Poland
J Clin Endocrinol Metab, February 2003, 88(2):950 –951
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References 1. Gasbarri A, Martegani MP, Del Prete F, Lucante T, Natali PG, Bartolazzi A 1999 Galectin-3 and CD44v6 isoforms in the preoperative evaluation of thyroid nodules. J Clin Oncol 17:3494 –3502 2. Bartolazzi A 2000 Improving accuracy of cytology for nodular thyroid lesions. Lancet 355:1661–1662 3. Bartolazzi A, Gasbarri A, Papotti M, Bussolati G, Lucante T, Khan A, Inohara H, Marandino F, Orlandi F, Nardi F, Vecchione A, Tecce R, Larsson O; Thyroid Cancer Study Group 2001 Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions. Lancet 357:1644 –1650 4. Niedziela M, Maceluch J, Korman E 2002 Galectin-3 is not an universal marker of malignancy in thyroid nodular disease in children and adolescents. J Clin Endocrinol Metab 87:4411– 4415 5. Herrmann ME, LiVolsi VA, Pasha TL, Roberts SA, Wojcik EM, Baloch ZW 2002 Immunohistochemical expression of galectin-3 in benign and malignant thyroid lesions. Arch Pathol Lab Med 126:710 –713 6. Beesley MF, McLaren KM 2002 Cytokeratin 19 and galectin-3 immunohistochemistry in the differential diagnosis of solitary thyroid nodules. Histopathology 41:236 –243 7. Bernet VJ, Anderson J, Vaishnav Y, Solomon B, Adair CF, Saji M, Burman KD, Burch HB, Ringel MD 2002 Determination of galectin-3 messenger ribonucleic acid overexpression in papillary thyroid cancer by quantitative reverse transcription-polymerase chain reaction. J Clin Endocrinol Metab 87: 4792– 4796 8. Martins L, Matsuo SE, Ebina KN, Kulcsar MA, Friguglietti CU, Kimura ET 2002 Galectin-3 messenger ribonucleic acid and protein are expressed in benign thyroid tumors. J Clin Endocrinol Metab 87:4806 – 4810
