Skip to main content
Erschienen in: Medical Oncology 1/2012

01.03.2012 | Original Paper

Cyclin A and cyclin B1 overexpression in differentiated thyroid carcinoma

verfasst von: Asli Nar, Ozlem Ozen, Neslihan Bascil Tutuncu, Beyhan Demirhan

Erschienen in: Medical Oncology | Ausgabe 1/2012

Einloggen, um Zugang zu erhalten

Abstract

Approximately 30% of patients with thyroid nodules have indeterminate or suspicious fine-needle aspiration (FNA) biopsy results. These patients usually undergo thyroidectomy because of cancer risk. Our aim was to determine diagnostic value of cyclin A and cyclin B1 immunohistochemistry added to routine cytology and their expression on histological sections. We studied the expression of cyclin A and cyclin B1 in FNA biopsies and resection specimens of 168 indeterminate or suspicious FNA biopsy results retrospectively at an academic hospital using immunohistochemistry. Malignant histopathology consisted 64 of resection specimens (58 papillary, 4 follicular, 1 medullary, and 1 Hürthle cell carcinoma). Cyclin A was overexpressed in 51.5% of malignant cases in contrast to 31.7% of 104 benign pathology specimens (P = 0.025). Cyclin B1 was positive in 39.1% of malignant specimens in contrast to 15.4% of benign cases (P = 0.001). Cyclin A overexpression was not linked to cyclin B1 overexpression. No association was found between overexpression of cyclin A, cyclin B1 and age, thyroiditis, multifocality, tumor size, extra-thyroidal extension, capsule infiltration, lymph node and distant organ metastases and TNM stage in malignant cases. Female patients with thyroid carcinoma overexpressed significantly more cyclin B1 than male patients (P = 0.015). Retrospective analysis of cyclin A and cyclin B1 in FNA biopsies yielded negative results for both benign and malignant cases. In conclusion, cyclin A and cyclin B1 are useful markers in the distinction of benign and malignant thyroid tumors and can increase diagnostic accuracy.
Literatur
1.
2.
Zurück zum Zitat Gharib H, Goellner JR. Fine-needle aspiration biopsy of the thyroid: an appraisal. Ann Intern Med. 1993;118:282–9.PubMed Gharib H, Goellner JR. Fine-needle aspiration biopsy of the thyroid: an appraisal. Ann Intern Med. 1993;118:282–9.PubMed
3.
Zurück zum Zitat Cersosimo E, Gharib H, Suman VJ, Goellner JR. “Suspicious” thyroid cytologic findings: outcome in patients without immediate surgical treatment. Mayo Clin Proc. 1993;68:343–8.PubMed Cersosimo E, Gharib H, Suman VJ, Goellner JR. “Suspicious” thyroid cytologic findings: outcome in patients without immediate surgical treatment. Mayo Clin Proc. 1993;68:343–8.PubMed
4.
Zurück zum Zitat Gharib H, Goellner JR, Johnson DA. Fine-needle aspiration cytology of the thyroid. A 12 year experience with 11,000 biopsies. Clin Lab Med. 1993;13:699–709.PubMed Gharib H, Goellner JR, Johnson DA. Fine-needle aspiration cytology of the thyroid. A 12 year experience with 11,000 biopsies. Clin Lab Med. 1993;13:699–709.PubMed
5.
Zurück zum Zitat Hooft L, Hoekstra OS, Boers M, Van Tulder MW, Van Diest P, Lips P. Practice, efficacy, and costs of thyroid nodule evaluation: a retrospective study in a Dutch university hospital. Thyroid. 2004;14:287–93.PubMedCrossRef Hooft L, Hoekstra OS, Boers M, Van Tulder MW, Van Diest P, Lips P. Practice, efficacy, and costs of thyroid nodule evaluation: a retrospective study in a Dutch university hospital. Thyroid. 2004;14:287–93.PubMedCrossRef
6.
Zurück zum Zitat Tuttle RM, Lemar H, Burch HB. Clinical features associated with an increased risk of thyroid malignancy in patients with follicular neoplasia by fine-needle aspiration. Thyroid. 1998;8:377–83.PubMedCrossRef Tuttle RM, Lemar H, Burch HB. Clinical features associated with an increased risk of thyroid malignancy in patients with follicular neoplasia by fine-needle aspiration. Thyroid. 1998;8:377–83.PubMedCrossRef
7.
Zurück zum Zitat Tyler DS, Winchester DJ, Caraway NP, Hickey RC, Evans DB. Indeterminate fine-needle aspiration biopsy of the thyroid: identification of subgroups at high risk for invasive carcinoma. Surgery. 1994;116:1054–60.PubMed Tyler DS, Winchester DJ, Caraway NP, Hickey RC, Evans DB. Indeterminate fine-needle aspiration biopsy of the thyroid: identification of subgroups at high risk for invasive carcinoma. Surgery. 1994;116:1054–60.PubMed
8.
Zurück zum Zitat Sanders LE, Cady B. Differentiated thyroid cancer: reexamination of risk groups and outcome of treatment. Arch Surg. 1998;133:419–25.PubMedCrossRef Sanders LE, Cady B. Differentiated thyroid cancer: reexamination of risk groups and outcome of treatment. Arch Surg. 1998;133:419–25.PubMedCrossRef
9.
Zurück zum Zitat Wiseman SM, Baliski C, Irvine R, Anderson D, Wilkins G, Filipenko D, Zhang H, Bugis S. Hemithyroidectomy: the optimal initial surgical approach for individuals undergoing surgery for a cytological diagnosis of follicular neoplasm. Ann Surg Oncol. 2006;13:425–32.PubMedCrossRef Wiseman SM, Baliski C, Irvine R, Anderson D, Wilkins G, Filipenko D, Zhang H, Bugis S. Hemithyroidectomy: the optimal initial surgical approach for individuals undergoing surgery for a cytological diagnosis of follicular neoplasm. Ann Surg Oncol. 2006;13:425–32.PubMedCrossRef
10.
Zurück zum Zitat Kebebew E, Peng M, Reiff E, McMillan A. Diagnostic and extent of disease multigene assay for malignant thyroid neoplasms. Cancer. 2006;106:2592–7.PubMedCrossRef Kebebew E, Peng M, Reiff E, McMillan A. Diagnostic and extent of disease multigene assay for malignant thyroid neoplasms. Cancer. 2006;106:2592–7.PubMedCrossRef
11.
Zurück zum Zitat 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. Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions. Lancet. 2001;357:1644–50.PubMedCrossRef 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. Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions. Lancet. 2001;357:1644–50.PubMedCrossRef
12.
Zurück zum Zitat de Matos PS, Ferreira AP, de Oliveira Facuri F, Assumpcao LV, Metze K, Ward LS. Usefulness of HBME-1, cytokeratin 19 and galectin-3 immunostaining in the diagnosis of thyroid malignancy. Histopathology. 2005;47:391–401.PubMedCrossRef de Matos PS, Ferreira AP, de Oliveira Facuri F, Assumpcao LV, Metze K, Ward LS. Usefulness of HBME-1, cytokeratin 19 and galectin-3 immunostaining in the diagnosis of thyroid malignancy. Histopathology. 2005;47:391–401.PubMedCrossRef
13.
Zurück zum Zitat Saggiorato E, De Pompa R, Volante M, Cappia S, Arecco F, Dei Tos AP, Orlandi F, Papotti M. Characterization of thyroid “follicular neoplasms” in fine-needle aspiration cytological specimens using a panel of immunohistochemical markers: a proposal for clinical application. Endocr Relat Cancer. 2005;12:305–17.PubMedCrossRef Saggiorato E, De Pompa R, Volante M, Cappia S, Arecco F, Dei Tos AP, Orlandi F, Papotti M. Characterization of thyroid “follicular neoplasms” in fine-needle aspiration cytological specimens using a panel of immunohistochemical markers: a proposal for clinical application. Endocr Relat Cancer. 2005;12:305–17.PubMedCrossRef
14.
Zurück zum Zitat Ito Y, Yoshida H, Tomoda C, Miya A, Kobayashi K, Matsuzuka F, Yasuoka H, Kakudo K, Inohara H, Kuma K, Miyauchi A. Galectin-3 expression in follicular tumours: an immunohistochemical study of its use as a marker of follicular carcinoma. Pathology. 2005;37:296–8.PubMedCrossRef Ito Y, Yoshida H, Tomoda C, Miya A, Kobayashi K, Matsuzuka F, Yasuoka H, Kakudo K, Inohara H, Kuma K, Miyauchi A. Galectin-3 expression in follicular tumours: an immunohistochemical study of its use as a marker of follicular carcinoma. Pathology. 2005;37:296–8.PubMedCrossRef
15.
Zurück zum Zitat Dutta A, Chandra R, Leiter LM, Lester S. Cyclins as markers of tumor proliferation: immunocytochemical studies in breast cancer. Proc Natl Acad Sci USA. 1995;92:5386–90.PubMedCrossRef Dutta A, Chandra R, Leiter LM, Lester S. Cyclins as markers of tumor proliferation: immunocytochemical studies in breast cancer. Proc Natl Acad Sci USA. 1995;92:5386–90.PubMedCrossRef
16.
Zurück zum Zitat Aaltomaa S, Eskelinen M, Lipponen P. Expression of cyclin A and D proteins in prostate cancer and their relation to clinicopathological variables and patient survival. Prostate. 1999;38:175–82.PubMedCrossRef Aaltomaa S, Eskelinen M, Lipponen P. Expression of cyclin A and D proteins in prostate cancer and their relation to clinicopathological variables and patient survival. Prostate. 1999;38:175–82.PubMedCrossRef
17.
Zurück zum Zitat Ito Y, Takeda T, Wakasa K, Tsujimoto M, Okada M, Matsuura N. Expression of the G2-M modulators in pancreatic adenocarcinoma. Pancreatology. 2002;2:138–45.PubMedCrossRef Ito Y, Takeda T, Wakasa K, Tsujimoto M, Okada M, Matsuura N. Expression of the G2-M modulators in pancreatic adenocarcinoma. Pancreatology. 2002;2:138–45.PubMedCrossRef
19.
Zurück zum Zitat Morgan DO. Principles of CDK regulation. Nature (Lond.). 1995;374:131–4.CrossRef Morgan DO. Principles of CDK regulation. Nature (Lond.). 1995;374:131–4.CrossRef
20.
Zurück zum Zitat Pines J, Hunter T. Cyclins A and B1 in the human cell cycle. Ciba Found Symp. 1992;170:187–204.PubMed Pines J, Hunter T. Cyclins A and B1 in the human cell cycle. Ciba Found Symp. 1992;170:187–204.PubMed
21.
Zurück zum Zitat Pines J, Hunter T. Human cyclin A is adenovirus E1A-associated protein p60 and behaves differently fromcyclin B. Nature. 1990;346:760–3.PubMedCrossRef Pines J, Hunter T. Human cyclin A is adenovirus E1A-associated protein p60 and behaves differently fromcyclin B. Nature. 1990;346:760–3.PubMedCrossRef
22.
Zurück zum Zitat Ito Y, Yoshida H, Nakano K, Takamura Y, Kobayashi K, Yokozawa T, Matsuzuka F, Matsuura N, Kuma K, Miyauchi A. Expression of G2-M modulators in thyroid neoplasms: correlation of cyclin A, B1 and cdc2 with differentiation. Pathol Res Pract. 2002;198:397–402.PubMedCrossRef Ito Y, Yoshida H, Nakano K, Takamura Y, Kobayashi K, Yokozawa T, Matsuzuka F, Matsuura N, Kuma K, Miyauchi A. Expression of G2-M modulators in thyroid neoplasms: correlation of cyclin A, B1 and cdc2 with differentiation. Pathol Res Pract. 2002;198:397–402.PubMedCrossRef
23.
Zurück zum Zitat Ito Y, Yoshida H, Matsuzuka F, Matsuura N, Nakamura Y, Nakamine H, Kakudo K, Kuma K, Miyauchi A. Cdc2 expression in primary thyroid lymphoma: its relationship with biological aggressiveness and G2 cyclins. Pathol Res Pract. 2003;199:533–8.PubMedCrossRef Ito Y, Yoshida H, Matsuzuka F, Matsuura N, Nakamura Y, Nakamine H, Kakudo K, Kuma K, Miyauchi A. Cdc2 expression in primary thyroid lymphoma: its relationship with biological aggressiveness and G2 cyclins. Pathol Res Pract. 2003;199:533–8.PubMedCrossRef
24.
Zurück zum Zitat Hooft L, van der Veldt AA, Hoekstra OS, Boers M, Molthoff CF, van Diest PJ. Hexokinase III cyclin A and galectin-3 are overexpressed in malignant follicular thyroid nodules. Clin Endocrinol (Oxf). 2008;68:252–7. Hooft L, van der Veldt AA, Hoekstra OS, Boers M, Molthoff CF, van Diest PJ. Hexokinase III cyclin A and galectin-3 are overexpressed in malignant follicular thyroid nodules. Clin Endocrinol (Oxf). 2008;68:252–7.
25.
Zurück zum Zitat Pulcrano M, Boukheris H, Talbot M, Caillou B, Dupuy C, Virion A, De Vathaire F, Schlumberger M. Poorly differentiated follicular thyroid carcinoma: prognostic factors and relevance of histological classification. Thyroid. 2007;17:639–46.PubMedCrossRef Pulcrano M, Boukheris H, Talbot M, Caillou B, Dupuy C, Virion A, De Vathaire F, Schlumberger M. Poorly differentiated follicular thyroid carcinoma: prognostic factors and relevance of histological classification. Thyroid. 2007;17:639–46.PubMedCrossRef
26.
Zurück zum Zitat Silver RJ, Parangi S. Management of thyroid incidentalomas. Surg Clin North Am. 2004;84:907–19.PubMedCrossRef Silver RJ, Parangi S. Management of thyroid incidentalomas. Surg Clin North Am. 2004;84:907–19.PubMedCrossRef
27.
Zurück zum Zitat Supid E, Peiris AN. Cost-effective management of thyroid nodules and nodular thyroid goiters. South Med J. 2002;95:514–9. Supid E, Peiris AN. Cost-effective management of thyroid nodules and nodular thyroid goiters. South Med J. 2002;95:514–9.
28.
Zurück zum Zitat McHenry CR, Thomas SR, Slusarczyk SJ, Khiyami A. Follicular or Hurthle cell neoplasm of the thyroid: can clinical factors be used to predict carcinoma and determine extent of thyroidectomy? Surgery. 1999;126:798–802. (discussion: 802–804).PubMedCrossRef McHenry CR, Thomas SR, Slusarczyk SJ, Khiyami A. Follicular or Hurthle cell neoplasm of the thyroid: can clinical factors be used to predict carcinoma and determine extent of thyroidectomy? Surgery. 1999;126:798–802. (discussion: 802–804).PubMedCrossRef
29.
Zurück zum Zitat Sahin M, Gursoy A, Tutuncu NB, Guvener DN. Prevalence and prediction of malignancy in cytologically indeterminate thyroid nodules. Clin Endocrinol (Oxf). 2006;65:514–8.CrossRef Sahin M, Gursoy A, Tutuncu NB, Guvener DN. Prevalence and prediction of malignancy in cytologically indeterminate thyroid nodules. Clin Endocrinol (Oxf). 2006;65:514–8.CrossRef
30.
Zurück zum Zitat Brzeziańska E, Cyniak-Magierska A, Sporny S, Pastuszak-Lewandoska D, Lewiński A. Assessment of cyclin D1 gene expression as a prognostic factor in benign and malignant thyroid lesions. Neuro Endocrinol Lett. 2007;28:341–50.PubMed Brzeziańska E, Cyniak-Magierska A, Sporny S, Pastuszak-Lewandoska D, Lewiński A. Assessment of cyclin D1 gene expression as a prognostic factor in benign and malignant thyroid lesions. Neuro Endocrinol Lett. 2007;28:341–50.PubMed
31.
Zurück zum Zitat Temmim L, Ebraheem AK, Baker H, Sinowatz F. Cyclin D1 protein expression in human thyroid gland and thyroid cancer. Anat Histol Embryol. 2006;35:125–9.PubMedCrossRef Temmim L, Ebraheem AK, Baker H, Sinowatz F. Cyclin D1 protein expression in human thyroid gland and thyroid cancer. Anat Histol Embryol. 2006;35:125–9.PubMedCrossRef
32.
Zurück zum Zitat Khoo ML, Ezzat S, Freeman JL, Asa SL. Cyclin D1 protein expression predicts metastatic behavior in thyroid papillary microcarcinomas but is not associated with gene amplification. J Clin Endocrinol Metab. 2002;87:1810–3.PubMedCrossRef Khoo ML, Ezzat S, Freeman JL, Asa SL. Cyclin D1 protein expression predicts metastatic behavior in thyroid papillary microcarcinomas but is not associated with gene amplification. J Clin Endocrinol Metab. 2002;87:1810–3.PubMedCrossRef
33.
Zurück zum Zitat Kebebew E, Reiff E, Duh QY, Clark OH, McMillan A. Extent of disease at presentation and outcome for adrenocortical carcinoma: have we made progress? World J Surg. 2006;30:872–8.PubMedCrossRef Kebebew E, Reiff E, Duh QY, Clark OH, McMillan A. Extent of disease at presentation and outcome for adrenocortical carcinoma: have we made progress? World J Surg. 2006;30:872–8.PubMedCrossRef
34.
Zurück zum Zitat Gong J, Ardelt B, Traganos F, Darzynkiewics Z. Unscheduled expression of cyclin B1 and cyclin E in several leukemic and solid tumor cell lines. Cancer Res. 1994;54:4285–8.PubMed Gong J, Ardelt B, Traganos F, Darzynkiewics Z. Unscheduled expression of cyclin B1 and cyclin E in several leukemic and solid tumor cell lines. Cancer Res. 1994;54:4285–8.PubMed
35.
Zurück zum Zitat Woodmansee WW, Kerr JM, Tucker EA, Mitchell JR, Haakinson DJ, Gordon DF, Ridgway EC, Wood WM. The proliferative status of thyrotropes ıs dependent on modulation of specific cell cycle regulators by thyroid hormone. Endocrinology. 2006;147:272–82.PubMedCrossRef Woodmansee WW, Kerr JM, Tucker EA, Mitchell JR, Haakinson DJ, Gordon DF, Ridgway EC, Wood WM. The proliferative status of thyrotropes ıs dependent on modulation of specific cell cycle regulators by thyroid hormone. Endocrinology. 2006;147:272–82.PubMedCrossRef
36.
Zurück zum Zitat Chao Y, Shih YL, Chiu JH, Chau GY, Lui WY, Yang WK, Lee SD, Huang TS. Overexpression of cyclin A but not Skp 2 correlates with the tumor relapse of human hepatocellular carcinoma. Cancer Res. 1998;58:985–90.PubMed Chao Y, Shih YL, Chiu JH, Chau GY, Lui WY, Yang WK, Lee SD, Huang TS. Overexpression of cyclin A but not Skp 2 correlates with the tumor relapse of human hepatocellular carcinoma. Cancer Res. 1998;58:985–90.PubMed
37.
Zurück zum Zitat Jin YH, Park CK. Expression of cyclin B1 and cdc2 in nodal non-Hodgkin’s lymphoma and its prognostic implications. J Korean Med Sci. 2002;17:322–7.PubMed Jin YH, Park CK. Expression of cyclin B1 and cdc2 in nodal non-Hodgkin’s lymphoma and its prognostic implications. J Korean Med Sci. 2002;17:322–7.PubMed
38.
Zurück zum Zitat Murakami H, Furihata M, Ohtsuki Y, Ogoshi S. Determination of the prognostic significance of cyclin B1 overexpression in patients with esophageal squamous cell carcinoma. Virchows Arch. 1999;434:153–8.PubMedCrossRef Murakami H, Furihata M, Ohtsuki Y, Ogoshi S. Determination of the prognostic significance of cyclin B1 overexpression in patients with esophageal squamous cell carcinoma. Virchows Arch. 1999;434:153–8.PubMedCrossRef
Metadaten
Titel
Cyclin A and cyclin B1 overexpression in differentiated thyroid carcinoma
verfasst von
Asli Nar
Ozlem Ozen
Neslihan Bascil Tutuncu
Beyhan Demirhan
Publikationsdatum
01.03.2012
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 1/2012
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-010-9800-0

Weitere Artikel der Ausgabe 1/2012

Medical Oncology 1/2012 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.