Información del artículo
La punción-aspiración con aguja fina (PAAF) es generalmente aceptada como la técnica de elección en el estudio del nódulo tiroideo; sin embargo, su interpretación clínica tiene algunas limitaciones. Por ello, en los últimos años se ha propuesto complementar la citología convencional con marcadores moleculares detectados mediante técnicas inmunoquímicas. Los marcadores más estudiados son TPO47 y galectina-3, ambos con notable sensibilidad y especificidad. CD44v6 es menos útil de lo que se pensaba al principio. Sobre pRB, c-Met, CK-19, HBME-1, COX-2 y hTERT, aunque muy prometedores, se dispone de menos experiencia. Existe una importante lista de otros potenciales marcadores de malignidad que están a la espera de ser analizados. Todos estos marcadores, empleados aisladamente o en combinación, podrían mejorar de manera sustancial la exactitud diagnóstica de la PAAF en los casos más difíciles y así evitar tiroidectomías innecesarias.
Palabras clave:
Tiroides
PAAF
TPO47
Galectina-3
Fine-needle aspiration biopsy (FNAB) is generally accepted as the method of choice for the study of thyroid nodule, but its clinical interpretation presents some limitations. For this reason, additional analyses of molecular markers using immunochemistry have been proposed in combination with conventional cytology. The best studied markers are TPO47 and galectin-3, both of which have remarkable sensitivity and specificity. CD44v6 seems to be less useful than was previously expected. Although pRB, c-Met, CK-19, HBME-1, COX-2 and hTERT are very promising, experience with these markers is limited. A long list of other potential markers of malignancy remain to be analyzed. All these markers, used alone or in combination, may substantially increase the diagnostic accuracy of FNAB in difficult cases and thus reduce unnecessary thyroidectomies.
Key words:
Thyroid
FNAB
TPO47
Galectin-3
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Biblografía
[1.]
E.L. Mazzaferri.
Management of a solitary thyroid nodule.
N Engl J Med, 328 (1993), pp. 553-559
[2.]
S.R. Orell, J. Philips.
The thyroid: fine-needle biopsy and cytological diagnosis of thyroid lesions.
[3.]
H. Gharib.
Fine-needle aspiration biopsy of thyroid nodules: advantages, limitations and effect.
Mayo Clin Proc, 69 (1994), pp. 44-49
[4.]
N.P. Caraway, N. Sneige, N.A. Samaam.
Diagnostic pitfalls in thyroid fine-needle aspiration: a review of 394 cases.
Diagn Cytophatol, 3 (1993), pp. 345-350
[5.]
M.K. Sidawy, D.M. Del Vechio, S.M. Knoll.
Fine-needle aspiration of thyroid nodules: correlation between cytology and histology and evaluation of discrepant cases.
Cancer, 81 (1997), pp. 253-259
[6.]
C. De Micco, J. Ruf, M.A. Chrestian, N. Gros, J.F. Henry, P. Carayon.
Immunohistochemical study of thyroid peroxidase in normal, hiperplastic, and neoplastic human thyroid tissues.
Cancer, 67 (1991), pp. 3036-3041
[7.]
C. De Micco, V. Vasko, S. García, P. Zoro, A. Denizot, J.F. Henry.
Fine-needle aspiration of thyroid follicular neoplasm: diagnostic use of thyroid peroxidase immunocytochemistry with monoclonal antibody 47.
Surgery, 116 (1994), pp. 1031-1035
[8.]
C. De Micco, P. Zoro, S. García, L. Skoog, E.M. Tani, P. Carayon, et al.
Thyroid peroxidase immunodetection as a tool to assist diagnosis of thyroid nodules on fine-needle aspiration biopsy.
Eur J Endocrinol, 131 (1994), pp. 474-479
[9.]
J.F. Henry, A. Denizot, A. Porcelli, M. Villafane, P. Zoro, S. García, et al.
Thyroperoxidase immunodetection for the diagnosis of malignancy on fine-needle aspiration of thyroid nodules.
World J Surg, 18 (1994), pp. 529-534
[10.]
M.J. Faroux, S. Theobald, M. Pluot, M. Patey, D. Menzies.
Evaluation of the monoclonal antibody antithyroperoxidase MoAb47 in the diagnosis decision of cold thyroid nodules by fine needle aspiration.
Pathol Res Pract, 193 (1997), pp. 705-712
[11.]
C. De Micco, V. Vassko, J.F. Henry.
The value of thyroid peroxidase immunohistochemistry for preoperative fine-needle aspiration diagnosis of the follicular variant of papillary thyroid cancer.
Surgery, 126 (1999), pp. 1200-1204
[12.]
L. Christensen, M. Blichert-Toft, M. Brandt, M. Lange, S.B. Sneppen, J. Ravnsbaek, et al.
Thyroperoxidase (TPO) immunostaining of the solitary cold thyroid nodule.
Clin Endocrinol, 53 (2000), pp. 161-169
[13.]
Y. Huang, M. Prasad, W.J. Lemon, H. Hampel, F.A. Wright, K. Kornacker, et al.
Gene expression in papillary thyroid carcinoma reveals highly consistent profiles.
Proc Natl Acad Sci USA, 98 (2001), pp. 15044-15049
[14.]
P. Vidal-Ríos, A. Rodríguez, L.H. Hofmann, X. Matías, T. Jiménez.
Primeras impresiones sobre la utilidad de la TPO47 en PAAF de nódulos tiroideos.
Endocrinol Nutr (Barc), 98 (2002), pp. 8
[15.]
P.L. Fernández, M.J. Merino, M. Gómez, E. Campo, T. Medina, V. Castronovo, et al.
Galectin-3 and laminin expression in neoplastic and non-neoplastic thyroid tissue.
J Pathol, 181 (1997), pp. 80-86
[16.]
F. Orlandi, E. Saggiorato, G. Pivano, B. Puligheddu, A. Termine, S. Cappia, et al.
Galectin is a presurgical marker of human thyroid carcinoma.
Cancer Res, 58 (1998), pp. 3015-3020
[17.]
H. Inohara, Y. Honjo, T. Yoshii, S. Akahani, J. Yoshida, K. Hattori, et al.
Expression of galectin-3 in fine-needle aspirates as a diagnostic marker differentiating benign from malignant thyroid neoplasms.
Cancer, 85 (1999), pp. 2475-2484
[18.]
A. Bartolazzi, A. Gasbarri, M. Papotti, G. Bussolati, T. Lucante, A. Khan, et al.
Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions.
Lancet, 357 (2001), pp. 1644-1650
[19.]
K. Kawachi, Y. Matsushita, S. Yonezawa, S. Nakano, K. Shirao, S. Natsugoe, et al.
Galectin-3 expression in various thyroid neoplasms and its possible role in metastasis formation.
Hum Pathol, 31 (2000), pp. 428-433
[20.]
A. Gasbarri, M.P. Martegani, F. Del Prete, T. Lucante, P.G. Natali, A. Bartolazzi.
Galectin-3 and CD44v6 isoforms in the preoperative evaluation of thyroid nodules.
J Clin Oncol, 17 (1999), pp. 3494-3502
[21.]
J. Figge, G. Bakst, D. Weisheit, O. Solis, J.S. Ross.
Image analysis quantitation of immunorreactive retinoblastoma protein in human thyroid neoplasms with a streptavidin-biotin-peroxidase staining technique.
Am J Pathol, 139 (1991), pp. 1213-1219
[22.]
T. Ogawa, Y. Hasegawa, B. Nakayama, Y. Fujimoto, T. Kohmura, H. Matsuura, et al.
An immunohistochemical study of RB suppressor gene protein and bcl-2 gene protein in carcinomas of the thyroid gland [abstract Medline].
Nippon Jibiinkoka Gakkai Kaiho, 101 (1998), pp. 595-601
[23.]
F. Anwar, M.J. Edmond, R.A. Schmidt, H.C. Hwuang, M.P. Bronner.
Retinoblastoma expression in thyroid neoplasms.
Mod Pathol, 13 (2000), pp. 562-569
[24.]
T. Oyama, E. Ichimura, T. Sano, K. Kashiwara, T. Fukuda, T. Nakajima.
c-Met expression of thyroid tissue with special reference to papillary carcinoma.
Pathol Int, 48 (1998), pp. 763-768
[25.]
A. Ippolito, V. Vella, G.L. La Rosa, G. Pellegriti, R. Vigneri, A. Belfiore.
Immunostaining for Met/HGF receptor may be useful to identify malignancies in thyroid lesions classified suspicious at fine-needle aspiration biopsy.
Thyroid, 11 (2001), pp. 783-787
[26.]
L.J.D.M. Schelfhout, G.N.P. Van Muijen, G.J. Fleuren.
Expression of keratin 19 distinguishes papillary thyroid carcinoma from follicular carcinoma and follicular thyroid adenoma.
Am J Clin Pathol, 92 (1989), pp. 654-659
[27.]
S.J. Rapheal, G. McKeown-Eyssen, S.L. Asa.
High molecularweight cytokeratin and cytokeratin-19 in the diagnosis of thyroid tumors.
Mod Pathol, 7 (1994), pp. 295-300
[28.]
S.M. Nasser, M. Pitman, B.Z. Pilch, W.C. Faquin.
Fine-needle aspiration biopsy of papillary thyroid carcinoma. Diagnostic utility of cytokeratin 19 immunostaining.
Cancer (Cancer cytopathology), 90 (2000), pp. 307-311
[29.]
C.C. Cheung, S. Ezzat, J.L. Freeman, I.B. Rosen, S.L. Asa.
Immunohistochemical diagnosis of papillary thyroid carcinoma.
Mod Pathol, 14 (2001), pp. 338-342
[30.]
M. Miettinen, P. Karkkainen.
Differential reactivity of HBME-1 and CD15 antibodies in benign and malignant thyroid tumours. Preferential reactivity with malignant tumours.
Virchows Arch, 429 (1996), pp. 213-219
[31.]
M.J. Sack, C. Astengo-Osuna, B.T. Lin, H. Battifora, V.A. LiVolsi.
HBME-1 immunostaining in thyroid fine-needle aspirations: a useful marker in the diagnosis of carcinoma.
Mod Pathol, 10 (1997), pp. 668-674
[32.]
V. Rigau, B. Martel, C. Evrard, P. Rousselot, F. Galateau-Salle.
HBME-1 immunostaining in thyroid pathology.
Ann Pathol, 21 (2001), pp. 15-20
[33.]
T. Hla, D. Bishop-Bailey, C.H. Liu, H.J. Schaefers, O.C. Trifan.
Cyclooxigenase- 1 and –2 isoenzymes.
Int J Biochem Cell Biol, 31 (1999), pp. 551-557
[34.]
R.G. Kurumbail, A.M. Stevens, J.K. Gierse.
Structural basis for selective inhibition of cyclooxigenase-2 by antiinflammatory agents.
Nature, 384 (1996), pp. 644-650
[35.]
M.C. Specht, O.N. Tucker, M. Hocever, D. González, L. Teng, T.J. Fahey.
3rd. Cyclooxygenase-2 expression in thyroid nodules.
J Clin Endocrinol Metab, 87 (2002), pp. 358-363
[36.]
A.J. Cornetta, J.P. Russell, M. Cunnane, W.M. Keane, J.L. Rothstein.
Cyclooxygenase-2 expression in human thyroid carcinoma and Hashimoto's thyroiditis.
Laryngoscope, 112 (2002), pp. 238-242
[37.]
F. Nose, T. Ichikawa, M. Fujiwara, I. Okayasu.
Up-regulation of cyclooxigenase-2 expression in lymphocytic thyroiditis and thyroid tumors: significant correlation with inducible nitric oxide synthase.
Am J Clin Pathol, 117 (2002), pp. 546-551
[38.]
J. Feng, W.D. Funk, S.S. Wang, S.L. Weinrich, A.A. Avilion, C.P. Chiu, et al.
The RNA component of human telomerase.
Science, 269 (1995), pp. 1236-1241
[39.]
S. Ramakrishnan, H.W. Sharma, A.D. Farris, K.M. Kaufman, J.B. Harley, K. Collins, et al.
Characterization of human telomerase complex.
Proc Natl Acad Sci, 94 (1997), pp. 10075-10079
[40.]
S. Le, R. Sternglanz, C.W. Greider.
Identification of two RNAbinding proteins associated with human telomerase RNA.
Mol Biol Cell, 11 (2000), pp. 999-1010
[41.]
M. Saji, S. Xydas, W.H. Westra, C.K. Liang, D.P. Clark, R. Udelsman, et al.
Human telomerase reverse transcriptase (hTERT) gene expression in thyroid neoplasms.
Clin Cancer Res, 5 (1999), pp. 1483-1489
[42.]
N.W. Kim, M.A. Piatyszek, K.R. Prowse, C.B. Harley, M.D. West, P.L.C. Ho, et al.
Specific association of human telomerase activity with immortal cells and cancer.
Science, 266 (1994), pp. 2011-2015
[43.]
C.B. Umbritcht, M. Saji, W.H. Westra, R. Udelsman, M.A. Zeiger, S. Sukumar.
Telomerase activity: a marker to distinguish follicular thyroid adenoma from carcinoma.
Cancer Res, 57 (1997), pp. 2144-2147
[44.]
J. Sebesta, T. Brown, W. Williard, M.J. Dehart, W. Aldous, J. Kavolius, et al.
Does telomerase activity add to the value of fine needle aspirations in evaluating thyroid nodules.
Am J Surg, 181 (2001), pp. 420-424
[45.]
P. Matthews, C.J. Jones, J. Skinner, M. Haughton, C. De Micco, D. Wyndford-Thomas.
Telomerase activity and telomere length in thyroid neoplasia: biological and clinical implications.
J Pathol, 194 (2001), pp. 183-193
[46.]
C. Hoang-Vu, C. Boltze, O. Gimm, C. Poremba, B. Dockhorn-Dworniczak, J. Kohrle, et al.
Expression of telomerase genes in thyroid carcinoma.
Int J Oncol, 21 (2002), pp. 265-272
[47.]
E. Hiyama, K. Hiyama.
Clinical utility of telomerase in cancer.
Oncogene, 21 (2002), pp. 643-649
[48.]
K. Aogi, K. Kitahara, V. Urquidi, D. Tarin, S. Goodison.
Comparison of telomerase and CD44 expression as diagnostic tumor markers in lesions of the thyroid.
Clin Cancer Res, 5 (1999), pp. 2790-2797
[49.]
M.A. Zeiger, R.C. Smallridge, D.P. Clark, C.K. Liang, S.E. Carty, C.G. Watson, et al.
Human telomerase reverse transcriptase (hTERT) gene expression in FNA samples from thyroid neoplasms.
Surgery, 126 (1999), pp. 1195-1198
[50.]
M.T. Siddiqui, K.L. Greene, D.P. Clark, S. Xydas, R. Udelsman, R.C. Smallridge, et al.
Human telomerase reverse transcriptase expression in Diff-Quik-stained FNA samples from thyroid nodules.
Diag Mol Pathol, 10 (2001), pp. 123-129
[51.]
E. Hiyama, K. Hiyama, T. Yokoyama, J.W. Shay.
Immunohistochemical detection of telomerase (hTERT) protein in human cancer tissues and a subset of cells in normal tissues.
Neoplasia, 3 (2001), pp. 17-23
[52.]
A.M. Straight, A. Patel, C. Fenton, C. Dinauer, R.M. Tuttle, G.L. Francis.
Thyroid carcinomas that express telomerase follow a more aggressive clinical course in children and adolescents.
J Endocrinol Invest, 25 (2002), pp. 302-308
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