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Erschienen in: Endocrine 1/2013

01.08.2013 | Original Article

BRAF V600E associates with cytoplasmatic localization of p27kip1 and higher cytokeratin 19 expression in papillary thyroid carcinoma

verfasst von: Anna Guerra, Vincenzo Marotta, Maurilio Deandrea, Manuela Motta, Paolo Piero Limone, Alessia Caleo, Pio Zeppa, Silvano Esposito, Franco Fulciniti, Mario Vitale

Erschienen in: Endocrine | Ausgabe 1/2013

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Abstract

The genetic alterations are responsible for the altered protein expression in tumors. The knowledge of the link between the altered protein expression and genetic alterations may provide potentially important biological and clinical information. In this study, the expression of some protein markers (Gal-3, p21Kip1, CK19) known to be associated to the papillary thyroid carcinoma (PTC) was assessed in a series of surgical samples by immunohistochemistry, and the association between expression of these markers and the BRAF V600E mutation was investigated. Gal-3 positive staining was evident in 26 % of benign nodules. The BRAF V600E mutation and Gal-3 expression, were found in 55.5 and 87 % of PTC respectively, and were unlinked. The expression of CK19 in benign nodules was weak and limited to scattered follicular cells. Diffuse cytoplasmatic expression of CK19 was present in malignant tumors in a variable percentage of cells. A higher percentage of CK19 expressing cells was associated with BRAF V600E (P ≤ 0.001). All benign nodules displayed nuclear p27kip1 in more than 15 % of the cells. Twenty-nine PTC showed a cytoplasmatic staining with negative nuclei. PTC with cytoplasmatic or 0–5 % of cells with nuclear staining, 6–15 % or >15 % of cells with nuclear staining were 72 (66.7 %), 24 (22.2 %), and 12 (11.1 %) respectively. In BRAF V600E positive tumors, the cytoplasmatic localization of p27kip1 was significantly more frequent (P = 0.024). In conclusion, we provide evidences that BRAF V600E is non-associated with Gal-3 expression, whereas it is associated with cytoplasmatic localization of p27kip1 and higher CK19 expression in PTC.
Literatur
1.
Zurück zum Zitat H. Gharib, J.R. Goellner, Fine-needle aspiration biopsy of the thyroid: an appraisal. Ann. Intern. Med. 118(4), 282–289 (1993)PubMedCrossRef H. Gharib, J.R. Goellner, Fine-needle aspiration biopsy of the thyroid: an appraisal. Ann. Intern. Med. 118(4), 282–289 (1993)PubMedCrossRef
2.
Zurück zum Zitat J.M. Miller, J.I. Hamburger, S. Kini, Diagnosis of thyroid nodules. Use of fine-needle aspiration and needle biopsy. JAMA 241(5), 481–484 (1979)PubMedCrossRef J.M. Miller, J.I. Hamburger, S. Kini, Diagnosis of thyroid nodules. Use of fine-needle aspiration and needle biopsy. JAMA 241(5), 481–484 (1979)PubMedCrossRef
3.
Zurück zum Zitat G. Jayaram, Fine needle aspiration cytologic study of the solitary thyroid nodule. Profile of 308 cases with histologic correlation. Acta Cytol. 29(6), 967–973 (1985)PubMed G. Jayaram, Fine needle aspiration cytologic study of the solitary thyroid nodule. Profile of 308 cases with histologic correlation. Acta Cytol. 29(6), 967–973 (1985)PubMed
4.
Zurück zum Zitat J.L. Wang, R.M. Gray, K.C. Haudek, R.J. Patterson, Nucleocytoplasmic lectins. Biochim. Biophys. Acta 1673(1–2), 75–93 (2004)PubMedCrossRef J.L. Wang, R.M. Gray, K.C. Haudek, R.J. Patterson, Nucleocytoplasmic lectins. Biochim. Biophys. Acta 1673(1–2), 75–93 (2004)PubMedCrossRef
5.
Zurück zum Zitat E. Saggiorato, S. Cappia, P. De Giuli, A. Mussa, G. Pancani, P. Caraci, A. Angeli, F. Orlandi, Galectin-3 as a presurgical immunocytodiagnostic marker of minimally invasive follicular thyroid carcinoma. J. Clin. Endocrinol. Metab. 86(11), 5152–5158 (2001)PubMedCrossRef E. Saggiorato, S. Cappia, P. De Giuli, A. Mussa, G. Pancani, P. Caraci, A. Angeli, F. Orlandi, Galectin-3 as a presurgical immunocytodiagnostic marker of minimally invasive follicular thyroid carcinoma. J. Clin. Endocrinol. Metab. 86(11), 5152–5158 (2001)PubMedCrossRef
6.
Zurück zum Zitat F. Orlandi, E. Saggiorato, G. Pivano, B. Puligheddu, A. Termine, S. Cappia, P. De Giuli, A. Angeli, Galectin-3 is a presurgical marker of human thyroid carcinoma. Cancer Res. 58(14), 3015–3020 (1998)PubMed F. Orlandi, E. Saggiorato, G. Pivano, B. Puligheddu, A. Termine, S. Cappia, P. De Giuli, A. Angeli, Galectin-3 is a presurgical marker of human thyroid carcinoma. Cancer Res. 58(14), 3015–3020 (1998)PubMed
7.
Zurück zum Zitat J. Bojunga, S. Zeuzem, Molecular detection of thyroid cancer: an update. Clin Endocrinol (Oxf) 61(5), 523–530 (2004)CrossRef J. Bojunga, S. Zeuzem, Molecular detection of thyroid cancer: an update. Clin Endocrinol (Oxf) 61(5), 523–530 (2004)CrossRef
8.
Zurück zum Zitat M. Niedziela, J. Maceluch, E. Korman, Galectin-3 is not an universal marker of malignancy in thyroid nodular disease in children and adolescents. J. Clin. Endocrinol. Metab. 87(9), 4411–4415 (2002)PubMedCrossRef M. Niedziela, J. Maceluch, E. Korman, Galectin-3 is not an universal marker of malignancy in thyroid nodular disease in children and adolescents. J. Clin. Endocrinol. Metab. 87(9), 4411–4415 (2002)PubMedCrossRef
9.
Zurück zum Zitat T. Takano, A. Miyauchi, F. Matsuzuka, H. Yoshida, K. Kuma, N. Amino, Ubiquitous expression of galectin-3 mRNA in benign and malignant thyroid tumors. Cancer Lett. 199(1), 69–73 (2003)PubMedCrossRef T. Takano, A. Miyauchi, F. Matsuzuka, H. Yoshida, K. Kuma, N. Amino, Ubiquitous expression of galectin-3 mRNA in benign and malignant thyroid tumors. Cancer Lett. 199(1), 69–73 (2003)PubMedCrossRef
10.
Zurück zum Zitat M. Pagano, S.W. Tam, A.M. Theodoras, P. Beer-Romero, G. Del Sal, V. Chau, P.R. Yew, G.F. Draetta, M. Rolfe, Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27. Science 269(5224), 682–685 (1995)PubMedCrossRef M. Pagano, S.W. Tam, A.M. Theodoras, P. Beer-Romero, G. Del Sal, V. Chau, P.R. Yew, G.F. Draetta, M. Rolfe, Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27. Science 269(5224), 682–685 (1995)PubMedCrossRef
11.
Zurück zum Zitat M. Loda, B. Cukor, S.W. Tam, P. Lavin, M. Fiorentino, G.F. Draetta, J.M. Jessup, M. Pagano, Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas. Nat. Med. 3(2), 231–234 (1997)PubMedCrossRef M. Loda, B. Cukor, S.W. Tam, P. Lavin, M. Fiorentino, G.F. Draetta, J.M. Jessup, M. Pagano, Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas. Nat. Med. 3(2), 231–234 (1997)PubMedCrossRef
12.
Zurück zum Zitat C. Catzavelos, N. Bhattacharya, Y.C. Ung, J.A. Wilson, L. Roncari, C. Sandhu, P. Shaw, H. Yeger, I. Morava-Protzner, L. Kapusta, E. Franssen, K.I. Pritchard, J.M. Slingerland, Decreased levels of the cell-cycle inhibitor p27Kip1 protein: prognostic implications in primary breast cancer. Nat. Med. 3(2), 227–230 (1997)PubMedCrossRef C. Catzavelos, N. Bhattacharya, Y.C. Ung, J.A. Wilson, L. Roncari, C. Sandhu, P. Shaw, H. Yeger, I. Morava-Protzner, L. Kapusta, E. Franssen, K.I. Pritchard, J.M. Slingerland, Decreased levels of the cell-cycle inhibitor p27Kip1 protein: prognostic implications in primary breast cancer. Nat. Med. 3(2), 227–230 (1997)PubMedCrossRef
13.
Zurück zum Zitat M. Mori, K. Mimori, T. Shiraishi, S. Tanaka, H. Ueo, K. Sugimachi, T. Akiyoshi, p27 expression and gastric carcinoma. Nat. Med. 3(6), 593 (1997)PubMedCrossRef M. Mori, K. Mimori, T. Shiraishi, S. Tanaka, H. Ueo, K. Sugimachi, T. Akiyoshi, p27 expression and gastric carcinoma. Nat. Med. 3(6), 593 (1997)PubMedCrossRef
14.
Zurück zum Zitat L.A. Erickson, L. Jin, P.C. Wollan, G.B. Thompson, J. van Heerden, R.V. Lloyd, Expression of p27kip1 and Ki-67 in benign and malignant thyroid tumors. Mod. Pathol. 11(2), 169–174 (1998)PubMed L.A. Erickson, L. Jin, P.C. Wollan, G.B. Thompson, J. van Heerden, R.V. Lloyd, Expression of p27kip1 and Ki-67 in benign and malignant thyroid tumors. Mod. Pathol. 11(2), 169–174 (1998)PubMed
15.
Zurück zum Zitat M.B. Resnick, P. Schacter, Y. Finkelstein, Y. Kellner, O. Cohen, Immunohistochemical analysis of p27/kip1 expression in thyroid carcinoma. Mod. Pathol. 11(8), 735–739 (1998)PubMed M.B. Resnick, P. Schacter, Y. Finkelstein, Y. Kellner, O. Cohen, Immunohistochemical analysis of p27/kip1 expression in thyroid carcinoma. Mod. Pathol. 11(8), 735–739 (1998)PubMed
16.
Zurück zum Zitat M.L. Khoo, N.J. Beasley, S. Ezzat, J.L. Freeman, S.L. Asa, Overexpression of cyclin D1 and under expression of p27 predict lymph node metastases in papillary thyroid carcinoma. J. Clin. Endocrinol. Metab. 87(4), 1814–1818 (2002)PubMedCrossRef M.L. Khoo, N.J. Beasley, S. Ezzat, J.L. Freeman, S.L. Asa, Overexpression of cyclin D1 and under expression of p27 predict lymph node metastases in papillary thyroid carcinoma. J. Clin. Endocrinol. Metab. 87(4), 1814–1818 (2002)PubMedCrossRef
17.
Zurück zum Zitat L.P. Zhong, S.F. Zhao, G.F. Chen, F.Y. Ping, Z.F. Xu, J.A. Hu, Increased levels of CK19 mRNA in oral squamous cell carcinoma tissue detected by relative quantification with real-time polymerase chain reaction. Arch. Oral Biol. 51(12), 1112–1119 (2006)PubMedCrossRef L.P. Zhong, S.F. Zhao, G.F. Chen, F.Y. Ping, Z.F. Xu, J.A. Hu, Increased levels of CK19 mRNA in oral squamous cell carcinoma tissue detected by relative quantification with real-time polymerase chain reaction. Arch. Oral Biol. 51(12), 1112–1119 (2006)PubMedCrossRef
18.
Zurück zum Zitat J. Rosai, Immunohistochemical markers of thyroid tumors: significance and diagnostic applications. Tumori 89(5), 517–519 (2003)PubMed J. Rosai, Immunohistochemical markers of thyroid tumors: significance and diagnostic applications. Tumori 89(5), 517–519 (2003)PubMed
19.
Zurück zum Zitat L.M. Brown, S.M. Helmke, S.W. Hunsucker, R.T. Netea-Maier, S.A. Chiang, D.E. Heinz, K.R. Shroyer, M.W. Duncan, B.R. Haugen, Quantitative and qualitative differences in protein expression between papillary thyroid carcinoma and normal thyroid tissue. Mol. Carcinog. 45(8), 613–626 (2006)PubMedCrossRef L.M. Brown, S.M. Helmke, S.W. Hunsucker, R.T. Netea-Maier, S.A. Chiang, D.E. Heinz, K.R. Shroyer, M.W. Duncan, B.R. Haugen, Quantitative and qualitative differences in protein expression between papillary thyroid carcinoma and normal thyroid tissue. Mol. Carcinog. 45(8), 613–626 (2006)PubMedCrossRef
20.
Zurück zum Zitat C.C. Cheung, S. Ezzat, J.L. Freeman, I.B. Rosen, S.L. Asa, Immunohistochemical diagnosis of papillary thyroid carcinoma. Mod. Pathol. 14(4), 338–342 (2001)PubMedCrossRef C.C. Cheung, S. Ezzat, J.L. Freeman, I.B. Rosen, S.L. Asa, Immunohistochemical diagnosis of papillary thyroid carcinoma. Mod. Pathol. 14(4), 338–342 (2001)PubMedCrossRef
21.
Zurück zum Zitat M. Xing, W.H. Westra, R.P. Tufano, Y. Cohen, E. Rosenbaum, K.J. Rhoden, K.A. Carson, V. Vasko, A. Larin, G. Tallini, S. Tolaney, E.H. Holt, P. Hui, C.B. Umbricht, S. Basaria, M. Ewertz, A.P. Tufaro, J.A. Califano, M.D. Ringel, M.A. Zeiger, D. Sidransky, P.W. Ladenson, BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer. J. Clin. Endocrinol. Metab. 90(12), 6373–6379 (2005)PubMedCrossRef M. Xing, W.H. Westra, R.P. Tufano, Y. Cohen, E. Rosenbaum, K.J. Rhoden, K.A. Carson, V. Vasko, A. Larin, G. Tallini, S. Tolaney, E.H. Holt, P. Hui, C.B. Umbricht, S. Basaria, M. Ewertz, A.P. Tufaro, J.A. Califano, M.D. Ringel, M.A. Zeiger, D. Sidransky, P.W. Ladenson, BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer. J. Clin. Endocrinol. Metab. 90(12), 6373–6379 (2005)PubMedCrossRef
22.
Zurück zum Zitat E.T. Kimura, M.N. Nikiforova, Z. Zhu, J.A. Knauf, Y.E. Nikiforov, J.A. Fagin, High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res. 63(7), 1454–1457 (2003)PubMed E.T. Kimura, M.N. Nikiforova, Z. Zhu, J.A. Knauf, Y.E. Nikiforov, J.A. Fagin, High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res. 63(7), 1454–1457 (2003)PubMed
23.
Zurück zum Zitat A. Guerra, M.R. Sapio, V. Marotta, E. Campanile, M.I. Moretti, M. Deandrea, M. Motta, P.P. Limone, G. Fenzi, G. Rossi, M. Vitale, Prevalence of RET/PTC rearrangement in benign and malignant thyroid nodules and its clinical application. Endocr. J. 58(1), 31–38 (2011)PubMedCrossRef A. Guerra, M.R. Sapio, V. Marotta, E. Campanile, M.I. Moretti, M. Deandrea, M. Motta, P.P. Limone, G. Fenzi, G. Rossi, M. Vitale, Prevalence of RET/PTC rearrangement in benign and malignant thyroid nodules and its clinical application. Endocr. J. 58(1), 31–38 (2011)PubMedCrossRef
24.
Zurück zum Zitat V. Marotta, A. Guerra, M.R. Sapio, M. Vitale, RET/PTC rearrangement in benign and malignant thyroid diseases: a clinical standpoint. Eur. J. Endocrinol. 165(4), 499–507 (2011). doi:10.1530/EJE-11-0499 PubMedCrossRef V. Marotta, A. Guerra, M.R. Sapio, M. Vitale, RET/PTC rearrangement in benign and malignant thyroid diseases: a clinical standpoint. Eur. J. Endocrinol. 165(4), 499–507 (2011). doi:10.​1530/​EJE-11-0499 PubMedCrossRef
25.
Zurück zum Zitat M.R. Sapio, A. Guerra, V. Marotta, E. Campanile, R. Formisano, M. Deandrea, M. Motta, P.P. Limone, G. Fenzi, G. Rossi, M. Vitale, High growth rate of benign thyroid nodules bearing RET/PTC rearrangements. J. Clin. Endocrinol. Metab. 96(6), E916–E919 (2011). doi:10.1210/jc.2010-1599 PubMedCrossRef M.R. Sapio, A. Guerra, V. Marotta, E. Campanile, R. Formisano, M. Deandrea, M. Motta, P.P. Limone, G. Fenzi, G. Rossi, M. Vitale, High growth rate of benign thyroid nodules bearing RET/PTC rearrangements. J. Clin. Endocrinol. Metab. 96(6), E916–E919 (2011). doi:10.​1210/​jc.​2010-1599 PubMedCrossRef
26.
Zurück zum Zitat V. Marotta, M.R. Sapio, A. Guerra, M. Vitale, BRAF mutation in cytology samples as a diagnostic tool for papillary thyroid carcinoma. Expert. Opin. Med. Diagn. 5(4), 277–290 (2011)PubMedCrossRef V. Marotta, M.R. Sapio, A. Guerra, M. Vitale, BRAF mutation in cytology samples as a diagnostic tool for papillary thyroid carcinoma. Expert. Opin. Med. Diagn. 5(4), 277–290 (2011)PubMedCrossRef
27.
Zurück zum Zitat N. Kurtulmus, M. Duren, U. Ince, M. Cengiz Yakicier, O. Peker, O. Aydin, E. Altiok, S. Giray, H. Azizlerli, BRAF(V600E) mutation in Turkish patients with papillary thyroid cancer: strong correlation with indicators of tumor aggressiveness. Endocrine 42(2), 404–410 (2012). doi:10.1007/s12020-012-9651-x PubMedCrossRef N. Kurtulmus, M. Duren, U. Ince, M. Cengiz Yakicier, O. Peker, O. Aydin, E. Altiok, S. Giray, H. Azizlerli, BRAF(V600E) mutation in Turkish patients with papillary thyroid cancer: strong correlation with indicators of tumor aggressiveness. Endocrine 42(2), 404–410 (2012). doi:10.​1007/​s12020-012-9651-x PubMedCrossRef
28.
Zurück zum Zitat A. Guerra, L. Fugazzola, V. Marotta, M. Cirillo, S. Rossi, V. Cirello, I. Forno, T. Moccia, A. Budillon, M. Vitale, A high percentage of BRAFV600E alleles in papillary thyroid carcinoma predicts a poorer outcome. J. Clin. Endocrinol. Metab. 97(7), 2333–2340 (2012). doi:10.1210/jc.2011-3106 PubMedCrossRef A. Guerra, L. Fugazzola, V. Marotta, M. Cirillo, S. Rossi, V. Cirello, I. Forno, T. Moccia, A. Budillon, M. Vitale, A high percentage of BRAFV600E alleles in papillary thyroid carcinoma predicts a poorer outcome. J. Clin. Endocrinol. Metab. 97(7), 2333–2340 (2012). doi:10.​1210/​jc.​2011-3106 PubMedCrossRef
29.
Zurück zum Zitat M.R. Sapio, A. Guerra, D. Posca, P.P. Limone, M. Deandrea, M. Motta, G. Troncone, A. Caleo, P. Vallefuoco, G. Rossi, G. Fenzi, M. Vitale, Combined analysis of galectin-3 and BRAFV600E improves the accuracy of fine-needle aspiration biopsy with cytological findings suspicious for papillary thyroid carcinoma. Endocr. Relat. Cancer 14(4), 1089–1097 (2007)PubMedCrossRef M.R. Sapio, A. Guerra, D. Posca, P.P. Limone, M. Deandrea, M. Motta, G. Troncone, A. Caleo, P. Vallefuoco, G. Rossi, G. Fenzi, M. Vitale, Combined analysis of galectin-3 and BRAFV600E improves the accuracy of fine-needle aspiration biopsy with cytological findings suspicious for papillary thyroid carcinoma. Endocr. Relat. Cancer 14(4), 1089–1097 (2007)PubMedCrossRef
30.
Zurück zum Zitat J. Rosai, M.L. Carcangiu, R.A. De Lellis, Tumors of the thyroid gland, in Atlas of tumor pathology third series fascicle 5, ed. by J. Rosai, L.H. Sobin (Armed Forces Institute of Pathology, Washington, 1992), pp. 49–62 J. Rosai, M.L. Carcangiu, R.A. De Lellis, Tumors of the thyroid gland, in Atlas of tumor pathology third series fascicle 5, ed. by J. Rosai, L.H. Sobin (Armed Forces Institute of Pathology, Washington, 1992), pp. 49–62
31.
Zurück zum Zitat M.R. Sapio, D. Posca, G. Troncone, G. Pettinato, L. Palombini, G. Rossi, G. Fenzi, M. Vitale, Detection of BRAF mutation in thyroid papillary carcinomas by mutant allele-specific PCR amplification (MASA). Eur. J. Endocrinol. 154(2), 341–348 (2006)PubMedCrossRef M.R. Sapio, D. Posca, G. Troncone, G. Pettinato, L. Palombini, G. Rossi, G. Fenzi, M. Vitale, Detection of BRAF mutation in thyroid papillary carcinomas by mutant allele-specific PCR amplification (MASA). Eur. J. Endocrinol. 154(2), 341–348 (2006)PubMedCrossRef
32.
Zurück zum Zitat A. Guerra, M.R. Sapio, V. Marotta, E. Campanile, S. Rossi, I. Forno, L. Fugazzola, A. Budillon, T. Moccia, G. Fenzi, M. Vitale, The primary occurrence of BRAFV600E is a rare clonal event in papillary thyroid carcinoma. J. Clin. Endocrinol. Metab. 97(2), 517–524 (2012). doi:10.1210/jc.2011-0618 PubMedCrossRef A. Guerra, M.R. Sapio, V. Marotta, E. Campanile, S. Rossi, I. Forno, L. Fugazzola, A. Budillon, T. Moccia, G. Fenzi, M. Vitale, The primary occurrence of BRAFV600E is a rare clonal event in papillary thyroid carcinoma. J. Clin. Endocrinol. Metab. 97(2), 517–524 (2012). doi:10.​1210/​jc.​2011-0618 PubMedCrossRef
33.
Zurück zum Zitat R.M. Melillo, M.D. Castellone, V. Guarino, V. De Falco, A.M. Cirafici, G. Salvatore, F. Caiazzo, F. Basolo, R. Giannini, M. Kruhoffer, T. Orntoft, A. Fusco, M. Santoro, The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells. J. Clin. Invest. 115(4), 1068–1081 (2005)PubMed R.M. Melillo, M.D. Castellone, V. Guarino, V. De Falco, A.M. Cirafici, G. Salvatore, F. Caiazzo, F. Basolo, R. Giannini, M. Kruhoffer, T. Orntoft, A. Fusco, M. Santoro, The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells. J. Clin. Invest. 115(4), 1068–1081 (2005)PubMed
34.
Zurück zum Zitat S. Akahani, P. Nangia-Makker, H. Inohara, H.R. Kim, A. Raz, Galectin-3: a novel antiapoptotic molecule with a functional BH1 (NWGR) domain of Bcl-2 family. Cancer Res. 57(23), 5272–5276 (1997)PubMed S. Akahani, P. Nangia-Makker, H. Inohara, H.R. Kim, A. Raz, Galectin-3: a novel antiapoptotic molecule with a functional BH1 (NWGR) domain of Bcl-2 family. Cancer Res. 57(23), 5272–5276 (1997)PubMed
35.
Zurück zum Zitat S.F. Dagher, J.L. Wang, R.J. Patterson, Identification of galectin-3 as a factor in pre-mRNA splicing. Proc. Natl. Acad. Sci. USA. 92(4), 1213–1217 (1995)PubMedCrossRef S.F. Dagher, J.L. Wang, R.J. Patterson, Identification of galectin-3 as a factor in pre-mRNA splicing. Proc. Natl. Acad. Sci. USA. 92(4), 1213–1217 (1995)PubMedCrossRef
36.
Zurück zum Zitat L. Chiariotti, M.T. Berlingieri, P. De Rosa, C. Battaglia, N. Berger, C.B. Bruni, A. Fusco, Increased expression of the negative growth factor, galactoside-binding protein, gene in transformed thyroid cells and in human thyroid carcinomas. Oncogene 7(12), 2507–2511 (1992)PubMed L. Chiariotti, M.T. Berlingieri, P. De Rosa, C. Battaglia, N. Berger, C.B. Bruni, A. Fusco, Increased expression of the negative growth factor, galactoside-binding protein, gene in transformed thyroid cells and in human thyroid carcinomas. Oncogene 7(12), 2507–2511 (1992)PubMed
37.
Zurück zum Zitat M.F. Beesley, K.M. McLaren, Cytokeratin 19 and galectin-3 immunohistochemistry in the differential diagnosis of solitary thyroid nodules. Histopathology 41(3), 236–243 (2002)PubMedCrossRef M.F. Beesley, K.M. McLaren, Cytokeratin 19 and galectin-3 immunohistochemistry in the differential diagnosis of solitary thyroid nodules. Histopathology 41(3), 236–243 (2002)PubMedCrossRef
38.
Zurück zum Zitat S.W. Blain, J. Massague, Breast cancer banishes p27 from nucleus. Nat. Med. 8(10), 1076–1078 (2002)PubMedCrossRef S.W. Blain, J. Massague, Breast cancer banishes p27 from nucleus. Nat. Med. 8(10), 1076–1078 (2002)PubMedCrossRef
39.
Zurück zum Zitat J. Slingerland, M. Pagano, Regulation of the cdk inhibitor p27 and its deregulation in cancer. J. Cell. Physiol. 183(1), 10–17 (2000)PubMedCrossRef J. Slingerland, M. Pagano, Regulation of the cdk inhibitor p27 and its deregulation in cancer. J. Cell. Physiol. 183(1), 10–17 (2000)PubMedCrossRef
40.
Zurück zum Zitat J. Vlach, S. Hennecke, B. Amati, Phosphorylation-dependent degradation of the cyclin-dependent kinase inhibitor p27. EMBO J. 16(17), 5334–5344 (1997)PubMedCrossRef J. Vlach, S. Hennecke, B. Amati, Phosphorylation-dependent degradation of the cyclin-dependent kinase inhibitor p27. EMBO J. 16(17), 5334–5344 (1997)PubMedCrossRef
41.
Zurück zum Zitat D. Vitagliano, F. Carlomagno, M.L. Motti, G. Viglietto, Y.E. Nikiforov, M.N. Nikiforova, J.M. Hershman, A.J. Ryan, A. Fusco, R.M. Melillo, M. Santoro, Regulation of p27Kip1 protein levels contributes to mitogenic effects of the RET/PTC kinase in thyroid carcinoma cells. Cancer Res. 64(11), 3823–3829 (2004)PubMedCrossRef D. Vitagliano, F. Carlomagno, M.L. Motti, G. Viglietto, Y.E. Nikiforov, M.N. Nikiforova, J.M. Hershman, A.J. Ryan, A. Fusco, R.M. Melillo, M. Santoro, Regulation of p27Kip1 protein levels contributes to mitogenic effects of the RET/PTC kinase in thyroid carcinoma cells. Cancer Res. 64(11), 3823–3829 (2004)PubMedCrossRef
42.
Zurück zum Zitat M.L. Motti, D. Califano, G. Troncone, C. De Marco, I. Migliaccio, E. Palmieri, L. Pezzullo, L. Palombini, A. Fusco, G. Viglietto, Complex regulation of the cyclin-dependent kinase inhibitor p27kip1 in thyroid cancer cells by the PI3K/AKT pathway: regulation of p27kip1 expression and localization. Am. J. Pathol. 166(3), 737–749 (2005)PubMedCrossRef M.L. Motti, D. Califano, G. Troncone, C. De Marco, I. Migliaccio, E. Palmieri, L. Pezzullo, L. Palombini, A. Fusco, G. Viglietto, Complex regulation of the cyclin-dependent kinase inhibitor p27kip1 in thyroid cancer cells by the PI3K/AKT pathway: regulation of p27kip1 expression and localization. Am. J. Pathol. 166(3), 737–749 (2005)PubMedCrossRef
43.
Zurück zum Zitat H.S. Jung, D.W. Kim, Y.S. Jo, H.K. Chung, J.H. Song, J.S. Park, K.C. Park, S.H. Park, J.H. Hwang, K.W. Jo, M. Shong, Regulation of protein kinase B tyrosine phosphorylation by thyroid-specific oncogenic RET/PTC kinases. Mol. Endocrinol. 19(11), 2748–2759 (2005)PubMedCrossRef H.S. Jung, D.W. Kim, Y.S. Jo, H.K. Chung, J.H. Song, J.S. Park, K.C. Park, S.H. Park, J.H. Hwang, K.W. Jo, M. Shong, Regulation of protein kinase B tyrosine phosphorylation by thyroid-specific oncogenic RET/PTC kinases. Mol. Endocrinol. 19(11), 2748–2759 (2005)PubMedCrossRef
44.
Zurück zum Zitat G. Crouzeix, J.J. Michels, E. Sevin, N. Aide, D. Vaur, S. Bardet, Unusual short-term complete response to two regimens of cytotoxic chemotherapy in a patient with poorly differentiated thyroid carcinoma. J. Clin. Endocrinol. Metab. 97(9), 3046–3050 (2012). doi:10.1210/jc.2012-1630 PubMedCrossRef G. Crouzeix, J.J. Michels, E. Sevin, N. Aide, D. Vaur, S. Bardet, Unusual short-term complete response to two regimens of cytotoxic chemotherapy in a patient with poorly differentiated thyroid carcinoma. J. Clin. Endocrinol. Metab. 97(9), 3046–3050 (2012). doi:10.​1210/​jc.​2012-1630 PubMedCrossRef
45.
Zurück zum Zitat V. Marotta, V. Ramundo, L. Camera, M.D. Prete, R. Fonti, R. Esposito, G. Palmieri, M. Salvatore, M. Vitale, A. Colao, A. Faggiano, Sorafenib in advanced iodine-refractory differentiated thyroid cancer: efficacy, safety and exploratory analysis of role of serum thyroglobulin and FDG-PET. Clin. Endocrinol. (Oxf) (2012). doi:10.1111/cen.12057 V. Marotta, V. Ramundo, L. Camera, M.D. Prete, R. Fonti, R. Esposito, G. Palmieri, M. Salvatore, M. Vitale, A. Colao, A. Faggiano, Sorafenib in advanced iodine-refractory differentiated thyroid cancer: efficacy, safety and exploratory analysis of role of serum thyroglobulin and FDG-PET. Clin. Endocrinol. (Oxf) (2012). doi:10.​1111/​cen.​12057
Metadaten
Titel
BRAF V600E associates with cytoplasmatic localization of p27kip1 and higher cytokeratin 19 expression in papillary thyroid carcinoma
verfasst von
Anna Guerra
Vincenzo Marotta
Maurilio Deandrea
Manuela Motta
Paolo Piero Limone
Alessia Caleo
Pio Zeppa
Silvano Esposito
Franco Fulciniti
Mario Vitale
Publikationsdatum
01.08.2013
Verlag
Springer US
Erschienen in
Endocrine / Ausgabe 1/2013
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-012-9843-4

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