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Published in: Pathology & Oncology Research 2/2013

01-04-2013 | Research

Significance of AgNORs and Ki-67 Proliferative Markers in Differential Diagnosis of Thyroid Lesions

Authors: Hayam A. Aiad, Manar A. Bashandy, Asmaa G. Abdou, Ahmad A. Zahran

Published in: Pathology & Oncology Research | Issue 2/2013

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Abstract

We aimed to assess the utility of quantitative analysis of AgNORs and Ki67 labeling index (LI) in the differential diagnosis of different thyroid lesions. This study included: 25 papillary carcinomas, 7 follicular carcinomas, 21 follicular adenomas and 27 nodular goiters. Using a semiautomatic image analysis system, Ag NORs parameters were measured and calculated including: total area of AgNORs, mean Ag NOR number in nuclei, nuclear area, mean area of AgNOR dots per each nucleus, number of central and marginal AgNOR dots, and the relative ratio of total area of AgNOR dots/total area of nucleus. Ki67 immunostaining was performed and the LI was determined. There was a significant difference between groups of thyroid lesions regarding total area of AgNORs, Ag NOR number and number of marginal Ag NOR dots. According to receiver operating characteristic curve, Ag NORs number =2.91 and marginal Ag NORs = 2.67 were useful cut off values above which follicular carcinoma can be diagnosed with 100 % sensitivity, 79 % specificity, 76 % PPV, 100 % NPV and 85 % diagnostic accuracy for both parameters. Mean Ki67 LI in our study was 14.12 ± 2.29, 61.42 ± 3.77, 34.90 ± 3.49 and 18.60 ± 1.96 for papillary carcinoma, follicular carcinoma, follicular adenoma and nodular goiter respectively. Ki67 LI showed statistically significant difference between follicular carcinoma and follicular adenoma (p = 0.026) and between papillary carcinoma and follicular adenoma (p = 0.007). Quantification of Ag NORs and Ki67 LI could be used as helpful ancillary methods in the differentiation between different thyroid lesions.
Literature
1.
go back to reference Baloch ZW, LiVolsi VA (2002) Follicular-patterned lesions of the thyroid: the bane of the pathologist. Am J Clin Pathol 117(1):143–150CrossRefPubMed Baloch ZW, LiVolsi VA (2002) Follicular-patterned lesions of the thyroid: the bane of the pathologist. Am J Clin Pathol 117(1):143–150CrossRefPubMed
2.
go back to reference Rosai J (2004) Thyroid gland. In: Rosai J (ed) Rosai and Ackerman’s surgical pathology, volume (2), Ch (9), 9th edn. Mosby, Edinburgh, pp 515–594 Rosai J (2004) Thyroid gland. In: Rosai J (ed) Rosai and Ackerman’s surgical pathology, volume (2), Ch (9), 9th edn. Mosby, Edinburgh, pp 515–594
3.
go back to reference Mase T, Funahashi H, Koshikawa T, Imai T, Nara Y, Tanaka Y, Nakao A (2003) HBME-1 immunostaining in thyroid tumors especially in follicular neoplasm. Endocr J 50(2):173–177CrossRefPubMed Mase T, Funahashi H, Koshikawa T, Imai T, Nara Y, Tanaka Y, Nakao A (2003) HBME-1 immunostaining in thyroid tumors especially in follicular neoplasm. Endocr J 50(2):173–177CrossRefPubMed
4.
go back to reference Rezk S, Brynes RK, Nelson V, Thein M, Patwardhan N, Fischer A, Khan A (2004) beta-Catenin expression in thyroid follicular lesions: potential role in nuclear envelope changes in papillary carcinomas. Endocr Pathol 15(4):329–337CrossRefPubMed Rezk S, Brynes RK, Nelson V, Thein M, Patwardhan N, Fischer A, Khan A (2004) beta-Catenin expression in thyroid follicular lesions: potential role in nuclear envelope changes in papillary carcinomas. Endocr Pathol 15(4):329–337CrossRefPubMed
5.
go back to reference Aiad HA, Kandil MA, Asaad NY, El-Kased AM, El-Goday SF (2008) Galectin-3 immunostaining in cytological and histopathological diagnosis of thyroid lesions. J Egypt Natl Canc Inst 20(1):36–46PubMed Aiad HA, Kandil MA, Asaad NY, El-Kased AM, El-Goday SF (2008) Galectin-3 immunostaining in cytological and histopathological diagnosis of thyroid lesions. J Egypt Natl Canc Inst 20(1):36–46PubMed
6.
go back to reference Rivera M, Ricarte-Filho J, Patel S, Tuttle M, Shaha A, Shah JP, Fagin JA, Ghossein RA (2010) Encapsulated thyroid tumors of follicular cell origin with high grade features (high mitotic rate/tumor necrosis): a clinicopathologic and molecular study. Hum Pathol 41(2):172–180CrossRefPubMed Rivera M, Ricarte-Filho J, Patel S, Tuttle M, Shaha A, Shah JP, Fagin JA, Ghossein RA (2010) Encapsulated thyroid tumors of follicular cell origin with high grade features (high mitotic rate/tumor necrosis): a clinicopathologic and molecular study. Hum Pathol 41(2):172–180CrossRefPubMed
7.
go back to reference Volante M, Collini P, Nikiforov YE, Sakamoto A, Kakudo K, Katoh R, Lloyd RV, LiVolsi VA, Papotti M, Sobrinho-Simoes M, Bussolati G, Rosai J (2007) Poorly differentiated thyroid carcinoma: the Turin proposal for the use of uniform diagnostic criteria and an algorithmic diagnostic approach. Am J Surg Pathol 31(8):1256–1264CrossRefPubMed Volante M, Collini P, Nikiforov YE, Sakamoto A, Kakudo K, Katoh R, Lloyd RV, LiVolsi VA, Papotti M, Sobrinho-Simoes M, Bussolati G, Rosai J (2007) Poorly differentiated thyroid carcinoma: the Turin proposal for the use of uniform diagnostic criteria and an algorithmic diagnostic approach. Am J Surg Pathol 31(8):1256–1264CrossRefPubMed
8.
go back to reference Sofiadis A, Tani E, Foukakis T, Kjellman P, Skoog L, Höög A, Wallin G, Zedenius J, Larsson C (2009) Diagnostic and prognostic potential of MIB-1 proliferation index in thyroid fine needle aspiration biopsy. Int J Oncol 35(2):369–374PubMed Sofiadis A, Tani E, Foukakis T, Kjellman P, Skoog L, Höög A, Wallin G, Zedenius J, Larsson C (2009) Diagnostic and prognostic potential of MIB-1 proliferation index in thyroid fine needle aspiration biopsy. Int J Oncol 35(2):369–374PubMed
9.
go back to reference Slowińska-Klencka D, Klencki M, Popowicz B, Sporny S, Lewiński A (2004) Multiparameter analysis of AgNOR in thyroid lesions: comparison with PCNA expression. Histol Histopathol 19(3):785–792PubMed Slowińska-Klencka D, Klencki M, Popowicz B, Sporny S, Lewiński A (2004) Multiparameter analysis of AgNOR in thyroid lesions: comparison with PCNA expression. Histol Histopathol 19(3):785–792PubMed
10.
go back to reference Mehrotra A, Goel MM, Singh K (2002) Ki-67 and AgNOR proliferative markers as diagnostic adjuncts to fine needle aspiration cytology of thyroid follicular lesions. Anal Quant Cytol Histol 24(4):205–211PubMed Mehrotra A, Goel MM, Singh K (2002) Ki-67 and AgNOR proliferative markers as diagnostic adjuncts to fine needle aspiration cytology of thyroid follicular lesions. Anal Quant Cytol Histol 24(4):205–211PubMed
11.
go back to reference Howell WM (1982) Selective staining of nucleolus organiser regions (NORs). In: Busch H, Rothblum L (eds) The cell nucleus. Vol IX. Academic, New York, pp 89–143 Howell WM (1982) Selective staining of nucleolus organiser regions (NORs). In: Busch H, Rothblum L (eds) The cell nucleus. Vol IX. Academic, New York, pp 89–143
12.
go back to reference Ploton D, Menager M, Jeannesson P, Himber G, Pigeon F, Adnet JJ (1986) Improvement in the staining and in the visualization of the argyrophilic proteins of the nucleolar organizer region at the optical level. Histochem J 18(1):5–14CrossRefPubMed Ploton D, Menager M, Jeannesson P, Himber G, Pigeon F, Adnet JJ (1986) Improvement in the staining and in the visualization of the argyrophilic proteins of the nucleolar organizer region at the optical level. Histochem J 18(1):5–14CrossRefPubMed
13.
go back to reference Bukhari MH, Niazi S, Khan SA, Hashmi I, Perveen S, Qureshi SS, Chaudhry NA, Qureshi GR, Hasan M (2007) Modified method of AgNOR staining for tissue and interpretation in histopathology. Int J Exp Pathol 88(1):47–53CrossRefPubMed Bukhari MH, Niazi S, Khan SA, Hashmi I, Perveen S, Qureshi SS, Chaudhry NA, Qureshi GR, Hasan M (2007) Modified method of AgNOR staining for tissue and interpretation in histopathology. Int J Exp Pathol 88(1):47–53CrossRefPubMed
14.
go back to reference Canet V, Montmasson MP, Usson Y, Giroud F, Brugal G (2001) Correlation between silver-stained nucleolar organizer region area and cell cycle time. Cytometry 43(2):110–116CrossRefPubMed Canet V, Montmasson MP, Usson Y, Giroud F, Brugal G (2001) Correlation between silver-stained nucleolar organizer region area and cell cycle time. Cytometry 43(2):110–116CrossRefPubMed
15.
go back to reference Kanematsu E, Matsui H, Deguchi T, Yamamoto O, Korematsu M, Kobayashi A, Nezasa S, Yamamoto N, Takeuchi T, Tanaka T, Kawada Y (1997) Signifcance of AgNOR counts for distinguishing carcinoma from adenoma and hyperplasia in parathyroid gland. Hum Pathol 28(4):421–427CrossRefPubMed Kanematsu E, Matsui H, Deguchi T, Yamamoto O, Korematsu M, Kobayashi A, Nezasa S, Yamamoto N, Takeuchi T, Tanaka T, Kawada Y (1997) Signifcance of AgNOR counts for distinguishing carcinoma from adenoma and hyperplasia in parathyroid gland. Hum Pathol 28(4):421–427CrossRefPubMed
16.
go back to reference Augustynowicz A, Dziecioł J, Barwijuk-Machała M, Dadan J, Puchalski Z, Sulkowski S (2004) Assessment of proliferative activity of thyroid Hürthle cell tumors using PCNA, Ki-67 and AgNOR methods. Folia Histochem Cytobiol 42(3):165–168PubMed Augustynowicz A, Dziecioł J, Barwijuk-Machała M, Dadan J, Puchalski Z, Sulkowski S (2004) Assessment of proliferative activity of thyroid Hürthle cell tumors using PCNA, Ki-67 and AgNOR methods. Folia Histochem Cytobiol 42(3):165–168PubMed
17.
go back to reference Kummoona R, Jabbar A, Kareem Al-Rahal D (2008) Proliferative activity in oral carcinomas studied with Ag-NOR and electron microscopy. Ultrastruct Pathol 32(4):139–146CrossRefPubMed Kummoona R, Jabbar A, Kareem Al-Rahal D (2008) Proliferative activity in oral carcinomas studied with Ag-NOR and electron microscopy. Ultrastruct Pathol 32(4):139–146CrossRefPubMed
18.
go back to reference Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H (1984) Cell cycle analysis of a cell proliferation associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133:1710–1715PubMed Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H (1984) Cell cycle analysis of a cell proliferation associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133:1710–1715PubMed
19.
go back to reference Kjellman P, Zedenius J, Lundell G, Backdahl M, Farnebo LO, Hamberger B, Larsson C, Wallin G (2006) Predictors of outcome in patients with papillary thyroid carcinoma. Eur J Surg Oncol 32(3):345–352CrossRefPubMed Kjellman P, Zedenius J, Lundell G, Backdahl M, Farnebo LO, Hamberger B, Larsson C, Wallin G (2006) Predictors of outcome in patients with papillary thyroid carcinoma. Eur J Surg Oncol 32(3):345–352CrossRefPubMed
20.
go back to reference Ito Y, Miyauchi A, Kakudo K, Hirokawa M, Kobayashi K, Miya A (2010) Prognostic significance of ki-67 labeling index in papillary thyroid carcinoma. World J Surg 34(12):3015–3021CrossRefPubMed Ito Y, Miyauchi A, Kakudo K, Hirokawa M, Kobayashi K, Miya A (2010) Prognostic significance of ki-67 labeling index in papillary thyroid carcinoma. World J Surg 34(12):3015–3021CrossRefPubMed
21.
go back to reference Mar KC, Eimoto T, Nagaya S, Tateyama H (2006) Cell proliferation marker MCM2, but not Ki67, is helpful for distinguishing between minimally invasive follicular carcinoma and follicular adenoma of the thyroid. Histopathology 48:801–807CrossRef Mar KC, Eimoto T, Nagaya S, Tateyama H (2006) Cell proliferation marker MCM2, but not Ki67, is helpful for distinguishing between minimally invasive follicular carcinoma and follicular adenoma of the thyroid. Histopathology 48:801–807CrossRef
22.
go back to reference Mehrotra P, Gonzalez MA, Johnson SJ, Coleman N, Wilson JA, Davies BR, Lennard TW (2006) Mcm-2 and Ki-67 have limited potential in preoperative diagnosis of thyroid malignancy. Laryngoscope 116:1434–1438CrossRefPubMed Mehrotra P, Gonzalez MA, Johnson SJ, Coleman N, Wilson JA, Davies BR, Lennard TW (2006) Mcm-2 and Ki-67 have limited potential in preoperative diagnosis of thyroid malignancy. Laryngoscope 116:1434–1438CrossRefPubMed
23.
go back to reference Królicka A, Kobierzycki C, Puła B, Podhorska-Okołów M, Piotrowska A, Rzeszutko M, Rzeszutko W, Rabczyński J, Domosławski P, Wojtczak B, Dawiskiba J, Dzięgiel P (2010) Comparison of metallothionein (MT) and Ki-67 antigen expression in benign and malignant thyroid tumours. Anticancer Res 30(12):4945–4949PubMed Królicka A, Kobierzycki C, Puła B, Podhorska-Okołów M, Piotrowska A, Rzeszutko M, Rzeszutko W, Rabczyński J, Domosławski P, Wojtczak B, Dawiskiba J, Dzięgiel P (2010) Comparison of metallothionein (MT) and Ki-67 antigen expression in benign and malignant thyroid tumours. Anticancer Res 30(12):4945–4949PubMed
24.
go back to reference Heikkilä A, Siironen P, Hagström J, Heiskanen I, Sankila R, Louhimo J, Haglund C, Arola J (2010) Follicular thyroid neoplasm: clinicopathologic features suggesting malignancy. APMIS 118(11):846–854CrossRefPubMed Heikkilä A, Siironen P, Hagström J, Heiskanen I, Sankila R, Louhimo J, Haglund C, Arola J (2010) Follicular thyroid neoplasm: clinicopathologic features suggesting malignancy. APMIS 118(11):846–854CrossRefPubMed
25.
go back to reference Pujani M, Arora B, Pujani M, Singh SK, Tejwani N (2010) Role of Ki-67 as a proliferative marker in lesions of thyroid. Indian J Cancer 47(3):304–307CrossRefPubMed Pujani M, Arora B, Pujani M, Singh SK, Tejwani N (2010) Role of Ki-67 as a proliferative marker in lesions of thyroid. Indian J Cancer 47(3):304–307CrossRefPubMed
26.
go back to reference Delellis RA, Lloyd RV, Heitz PU, Eng C (eds) (2004) World Health Organization classification of tumors. Pathology and genetics of tumors of endocrine organs. IARC Press, Lyon Delellis RA, Lloyd RV, Heitz PU, Eng C (eds) (2004) World Health Organization classification of tumors. Pathology and genetics of tumors of endocrine organs. IARC Press, Lyon
27.
go back to reference Aubele M, Biesterfeld S, Derenzini M, Hufnagl P, Martin H, Ofner D, Ploton D, Ruschoff J (1994) Guidelines of AgNOR quantitation. Zentralbl Pathol 140:107–108PubMed Aubele M, Biesterfeld S, Derenzini M, Hufnagl P, Martin H, Ofner D, Ploton D, Ruschoff J (1994) Guidelines of AgNOR quantitation. Zentralbl Pathol 140:107–108PubMed
28.
go back to reference Hufnagl P, Guski H, Schulz HJ (1994) Measuring of AgNORs using image analysis. Zentralbl Pathol 140(1):31–35PubMed Hufnagl P, Guski H, Schulz HJ (1994) Measuring of AgNORs using image analysis. Zentralbl Pathol 140(1):31–35PubMed
29.
go back to reference Słowińska-Klencka D, Klencki M, Popowicz B, Lewiński A (2003) AgNOR quantification in the diagnosis of follicular pattern thyroid lesions. Anal Quant Cytol Histol 25(6):347–352PubMed Słowińska-Klencka D, Klencki M, Popowicz B, Lewiński A (2003) AgNOR quantification in the diagnosis of follicular pattern thyroid lesions. Anal Quant Cytol Histol 25(6):347–352PubMed
30.
go back to reference Solymosi T, Toth V, Sapi Z, Bodo M, Gal I, Csanate L (1996) Diagnostic value of AgNORs method in thyroid cytopathology: correlation with morphometric measurements. Diagn Cytopathol 14:140–144CrossRefPubMed Solymosi T, Toth V, Sapi Z, Bodo M, Gal I, Csanate L (1996) Diagnostic value of AgNORs method in thyroid cytopathology: correlation with morphometric measurements. Diagn Cytopathol 14:140–144CrossRefPubMed
31.
go back to reference Asorta S, Sharma J (2008) Role of AgNors in thyroid lesions on fine needle aspiration cytology smears. J Cytol 25:18–22CrossRef Asorta S, Sharma J (2008) Role of AgNors in thyroid lesions on fine needle aspiration cytology smears. J Cytol 25:18–22CrossRef
32.
go back to reference Cornianu M, Milos L, Golu L, Taban S, Milos A (2006) Proliferative activity of thyroid hurthle cell tumors. Acta Endocrinologica (Buc) 3:269–282CrossRef Cornianu M, Milos L, Golu L, Taban S, Milos A (2006) Proliferative activity of thyroid hurthle cell tumors. Acta Endocrinologica (Buc) 3:269–282CrossRef
33.
go back to reference Lewy-Trenda I, Janezukowics J, Wierzchniewska L (2006) Practical application of proliferation markers (MIB-I, PCNA, AgNOR) expression analysis of differential diagnostics of nodular thyroid lesions. Wiad Lek 59(1-2):32–37, abstractPubMed Lewy-Trenda I, Janezukowics J, Wierzchniewska L (2006) Practical application of proliferation markers (MIB-I, PCNA, AgNOR) expression analysis of differential diagnostics of nodular thyroid lesions. Wiad Lek 59(1-2):32–37, abstractPubMed
34.
go back to reference Ciobanu D, Căruntu ID, Vulpoi C, Florea N, Giuşcă SE (2006) Morphometric parameters and silver stain used in diagnosis of thyroid follicular diseases. Rom J Morphol Embryol 47(4):323–330PubMed Ciobanu D, Căruntu ID, Vulpoi C, Florea N, Giuşcă SE (2006) Morphometric parameters and silver stain used in diagnosis of thyroid follicular diseases. Rom J Morphol Embryol 47(4):323–330PubMed
35.
go back to reference Rüschoff J, Prasser C, Cortez T, Höhne HM, Hohenberger W, Hofstädter F (1993) Diagnostic value of AgNOR staining in follicular cell neoplasms of the thyroid: comparison of evaluation methods and nucleolar features. Am J Surg Pathol 17(12):1281–1288CrossRefPubMed Rüschoff J, Prasser C, Cortez T, Höhne HM, Hohenberger W, Hofstädter F (1993) Diagnostic value of AgNOR staining in follicular cell neoplasms of the thyroid: comparison of evaluation methods and nucleolar features. Am J Surg Pathol 17(12):1281–1288CrossRefPubMed
36.
go back to reference Hepburn PJ, Glynne-Jones E, Goddard L, Gee JM, Harper ME (1995) Cell proliferation in prostatic carcinoma: comparative analysis of Ki-67, MIB-1 and PCNA. Histochem J 27(3):196–203PubMed Hepburn PJ, Glynne-Jones E, Goddard L, Gee JM, Harper ME (1995) Cell proliferation in prostatic carcinoma: comparative analysis of Ki-67, MIB-1 and PCNA. Histochem J 27(3):196–203PubMed
37.
go back to reference Ronckers C, Ron E (2006) Thyroid cancer. In, Freedman LS, Edwards BK, Ries LAG, Young JL (eds). Cancer Incidence in Four Member Countries (Cyprus, Egypt, Israel, and Jordan) of the Middle East Cancer Consortium (MECC) Compared with US SEER. National Cancer Institute. NIH Pub. No. 06-5873. Bethesda, MD, pp 121–130 Ronckers C, Ron E (2006) Thyroid cancer. In, Freedman LS, Edwards BK, Ries LAG, Young JL (eds). Cancer Incidence in Four Member Countries (Cyprus, Egypt, Israel, and Jordan) of the Middle East Cancer Consortium (MECC) Compared with US SEER. National Cancer Institute. NIH Pub. No. 06-5873. Bethesda, MD, pp 121–130
38.
go back to reference Erickson LA, Jin L, Wollan PC, Thompson GB, van Heerden J, Lloyd RV (1998) Expression of p27/kip1 and Ki-67 in benign and malignant thyroid tumors. Mod Pathol 11(2):169–174PubMed Erickson LA, Jin L, Wollan PC, Thompson GB, van Heerden J, Lloyd RV (1998) Expression of p27/kip1 and Ki-67 in benign and malignant thyroid tumors. Mod Pathol 11(2):169–174PubMed
39.
go back to reference Erickson LA, Jin L, Goellner JR, Lohse C, Pankratz VS, Zukerberg LR, Thompson GB, van Heerden JA, Grant CS, Lloyd R (2000) Pathologic features, proliferative activity, and cyclin D1 expression in Hurthle cell neoplasms of the thyroid. Mod Pathol 13(2):186–192CrossRefPubMed Erickson LA, Jin L, Goellner JR, Lohse C, Pankratz VS, Zukerberg LR, Thompson GB, van Heerden JA, Grant CS, Lloyd R (2000) Pathologic features, proliferative activity, and cyclin D1 expression in Hurthle cell neoplasms of the thyroid. Mod Pathol 13(2):186–192CrossRefPubMed
40.
go back to reference Horii A, Yoshida J, Sakai M, Okamoto S, Honjo Y, Mitani K, Hattori K, Kubo T (1999) Ki-67 positive fractions in benign and malignant thyroid tumours: application of flow cytometry. Acta Otolaryngol 119(5):617–620CrossRefPubMed Horii A, Yoshida J, Sakai M, Okamoto S, Honjo Y, Mitani K, Hattori K, Kubo T (1999) Ki-67 positive fractions in benign and malignant thyroid tumours: application of flow cytometry. Acta Otolaryngol 119(5):617–620CrossRefPubMed
41.
go back to reference Rickert D, Mittermayer C, Lindenfelser R, Biesterfeld S (2000) MIB-1 immunohistometry of follicular adenoma and follicular carcinoma of the thyroid gland. Anal Quant Cytol Histol 22(3):229–234PubMed Rickert D, Mittermayer C, Lindenfelser R, Biesterfeld S (2000) MIB-1 immunohistometry of follicular adenoma and follicular carcinoma of the thyroid gland. Anal Quant Cytol Histol 22(3):229–234PubMed
42.
go back to reference Erickson LA, Yousef OM, Jin L, Lohse CM, Pankratz VS, Lloyd RV (2000) p27kip1 expression distinguishes papillary hyperplasia in Graves’ disease from papillary thyroid carcinoma. Mod Pathol 13(9):1014–1019CrossRefPubMed Erickson LA, Yousef OM, Jin L, Lohse CM, Pankratz VS, Lloyd RV (2000) p27kip1 expression distinguishes papillary hyperplasia in Graves’ disease from papillary thyroid carcinoma. Mod Pathol 13(9):1014–1019CrossRefPubMed
43.
go back to reference Zidan J, Karen D, Stein M, Rosenblatt E, Basher W, Kuten A (2003) Pure versus follicular variant of papillary thyroid carcinoma: clinical features, prognostic factors, treatment and survival. Cancer 97(5):1181–1185CrossRefPubMed Zidan J, Karen D, Stein M, Rosenblatt E, Basher W, Kuten A (2003) Pure versus follicular variant of papillary thyroid carcinoma: clinical features, prognostic factors, treatment and survival. Cancer 97(5):1181–1185CrossRefPubMed
Metadata
Title
Significance of AgNORs and Ki-67 Proliferative Markers in Differential Diagnosis of Thyroid Lesions
Authors
Hayam A. Aiad
Manar A. Bashandy
Asmaa G. Abdou
Ahmad A. Zahran
Publication date
01-04-2013
Publisher
Springer Netherlands
Published in
Pathology & Oncology Research / Issue 2/2013
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-012-9565-1

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