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Published in: Diagnostic Pathology 1/2008

Open Access 01-12-2008 | Research

Application of CD56, P63 and CK19 immunohistochemistry in the diagnosis of papillary carcinoma of the thyroid

Authors: Dina El Demellawy, Ahmed Nasr, Salem Alowami

Published in: Diagnostic Pathology | Issue 1/2008

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Abstract

Papillary carcinoma of the thyroid (PTC) is the commonest thyroid cancer. In the recent decades an obvious increase in the incidence of PTC has occurred. The pathological diagnosis of PTC is usually an easy diagnosis in the majority of cases. However since the introduction of follicular variant of PTC and the wide threshold range in interpretation of the clearly set pathological criteria for diagnosis of PTC, between pathologists including experts, the diagnosis in some cases became quite difficult. Unfortunately some cases are unjustifiably over-called as follicular variant of PTC as a result of the wide inter observable variability between pathologists, including thyroid pathologists.
Ancillary studies such as immmunohistochemistry may be helpful, but till now there is no 100% consistent marker(s), that distinct between PTC and other follicular thyroid lesions and tumors.
We assessed expression of antibodies against CD56, CK19, P63 and E-Cadherin in PTC and other follicular thyroid lesions and neoplasms. A total of 175 cases were studied. The neoplastic cases included 75 carcinomas (72 papillary, 2 follicular, 1 Hurthle cell) and 35 adenomas (32 follicular and 3 Hurthle cell). The non-neoplastic thyroids included 65 cases, (25 nodular hyperplasia, 5 thyrotoxic hyperplasia (Grave's disease), 19 lymphocytic thyroiditis and 6 Hashimoto's thyroiditis). All cases were evaluated by immunohistochemistry for the expression of the above mentioned markers. The markers' patterns and intensities of staining were scored. Positive expression of the markers equal or >10% of the follicular epithelium within the tumor or lesional cells was considered positive. An expression of <10% was considered to be negative.
Our results showed CD56 positive in all the lesions and tumors except for PTC in all cases (100%). CD56 was negative in all PTC cases (100%). CK 19 showed positive expression in PTC accounting for 85% of cases and in 26% of non PTC lesions/tumors. P63 showed selective focal positivity in PTC cases, in contrast to other non PTC lesions/tumors. P63 expression was in 70% of cases of PTC and was consistently absent in all the non PTC cases. E-Cadherin showed consistent non discriminatory expression in all cases included in the study.
We concluded that a panel consisted of CD56, CK19 and P63 is of value in distinction of PTC from other thyroid follicular lesion. P63 is a specific but less sensitive marker for PTC than CK19. CD56 is more specific and sensitive marker than CK19, however it is a negative rather than a positive marker for PTC. E-Cadherin is of no value in the diagnosis of thyroid follicular lesions/tumors. We recommend application of a panel composed of CK19, P63 and CD56 by a group of expert thyroid pathologists on a large series of follicular malignant thyroid neoplasms of uncertain malignant.
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Literature
1.
go back to reference Lloyd RV, Erikson LA, Casey MB, Lam KY, Lohse CM, Asa SL, Chan JK, DeLellis RA, Harach HR, Kakudo K, LiVolsi VA, Rosai J, Sebo TJ, Sobrinho-Simoes M, Wenig BM, Lae ME: Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma. Am J Surg Pathol. 2004, 28 (10): 1336-1340. 10.1097/01.pas.0000135519.34847.f6.CrossRefPubMed Lloyd RV, Erikson LA, Casey MB, Lam KY, Lohse CM, Asa SL, Chan JK, DeLellis RA, Harach HR, Kakudo K, LiVolsi VA, Rosai J, Sebo TJ, Sobrinho-Simoes M, Wenig BM, Lae ME: Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma. Am J Surg Pathol. 2004, 28 (10): 1336-1340. 10.1097/01.pas.0000135519.34847.f6.CrossRefPubMed
2.
go back to reference Hirokawa M, Carney JA, Goellner JR, DeLellis RA, Heffess CS, Katoh R, Tsujimoto M, Kakudo K: Observer variation in encapsulated follicular lesions of the thyroid. Am J Surg Pathol. 2002, 26: 1508-1514. 10.1097/00000478-200211000-00014.CrossRefPubMed Hirokawa M, Carney JA, Goellner JR, DeLellis RA, Heffess CS, Katoh R, Tsujimoto M, Kakudo K: Observer variation in encapsulated follicular lesions of the thyroid. Am J Surg Pathol. 2002, 26: 1508-1514. 10.1097/00000478-200211000-00014.CrossRefPubMed
3.
go back to reference Chen KT, Rosai J: Follicular variant of thyroid papillary carcinoma: a clinicopathological study of six cases. Am J Surg Pathol. 1977, 1: 123-130.CrossRef Chen KT, Rosai J: Follicular variant of thyroid papillary carcinoma: a clinicopathological study of six cases. Am J Surg Pathol. 1977, 1: 123-130.CrossRef
4.
go back to reference Crile GJ, Hazard J: Relationship of the age of patient to natural history and prognosis of carcinoma of the thyroid. Am Surg. 1953, 138: 33-38. Crile GJ, Hazard J: Relationship of the age of patient to natural history and prognosis of carcinoma of the thyroid. Am Surg. 1953, 138: 33-38.
5.
go back to reference Cavallaro U, Niedermayer J, Fuxa M, Christofori G: N-CAM modulates tumour-cell adhesion to matrix by inducing FGFreceptor signalling. Nature Cell Biol. 2001, 3: 650-657. 10.1038/35083041.CrossRefPubMed Cavallaro U, Niedermayer J, Fuxa M, Christofori G: N-CAM modulates tumour-cell adhesion to matrix by inducing FGFreceptor signalling. Nature Cell Biol. 2001, 3: 650-657. 10.1038/35083041.CrossRefPubMed
6.
go back to reference Rutishauser U, Acheson A, Hall AK, Mann DM, Sunshine J: The neural cell adhesion molecule (NCAM) as a regulator of cell-cell interactions. Science. 1988, 240: 53-57. 10.1126/science.3281256.CrossRefPubMed Rutishauser U, Acheson A, Hall AK, Mann DM, Sunshine J: The neural cell adhesion molecule (NCAM) as a regulator of cell-cell interactions. Science. 1988, 240: 53-57. 10.1126/science.3281256.CrossRefPubMed
7.
go back to reference Levrero M, De Laurenzi V, Costanzo A, Gong J, Wang JY, Melino G: The p53/p63/p73 family of transcription factors: overlapping and distinct functions. J Cell Sci. 2000, 113: 1661-1670.PubMed Levrero M, De Laurenzi V, Costanzo A, Gong J, Wang JY, Melino G: The p53/p63/p73 family of transcription factors: overlapping and distinct functions. J Cell Sci. 2000, 113: 1661-1670.PubMed
8.
go back to reference Reis-Filho JS, Schmitt FC: Taking advantage of basic research: p63 is a reliable myoepithelial and stem cell marker. Adv Anat Pathol. 2002, 9: 280-289. 10.1097/00125480-200209000-00002.CrossRefPubMed Reis-Filho JS, Schmitt FC: Taking advantage of basic research: p63 is a reliable myoepithelial and stem cell marker. Adv Anat Pathol. 2002, 9: 280-289. 10.1097/00125480-200209000-00002.CrossRefPubMed
9.
go back to reference Di Como CJ, Urist MJ, Babayan I, Drobnjak M, Hedvat CV, Teruya-Feldstein J, Pohar K, Hoos A, Cordon-Cardo C: p63 Expression Profiles in Human Normal and Tumor Tissues. Clin Cancer Res. 2002, 8: 494-501.PubMed Di Como CJ, Urist MJ, Babayan I, Drobnjak M, Hedvat CV, Teruya-Feldstein J, Pohar K, Hoos A, Cordon-Cardo C: p63 Expression Profiles in Human Normal and Tumor Tissues. Clin Cancer Res. 2002, 8: 494-501.PubMed
10.
go back to reference Preto A, Reis-Filho JS, Ricardo S, Soares P: p63 expression in papillary and anaplastic carcinomas of the thyroid gland: lack of an oncogenetic role in tumorigenesis and progression. Pathol Res Pract. 2002, 198: 449-454. 10.1078/0344-0338-00281.CrossRefPubMed Preto A, Reis-Filho JS, Ricardo S, Soares P: p63 expression in papillary and anaplastic carcinomas of the thyroid gland: lack of an oncogenetic role in tumorigenesis and progression. Pathol Res Pract. 2002, 198: 449-454. 10.1078/0344-0338-00281.CrossRefPubMed
11.
go back to reference Mills AA, Zheng B, Wang XJ, Vogel H, Roop DR, Bradley A: p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature. 1999, 398: 708-713. 10.1038/19531.CrossRefPubMed Mills AA, Zheng B, Wang XJ, Vogel H, Roop DR, Bradley A: p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature. 1999, 398: 708-713. 10.1038/19531.CrossRefPubMed
12.
go back to reference Stone MR, O'Neill A, Catino D, Bloch RJ: Specific interaction of the actin-binding domain of dystrophin with intermediate filaments containing keratin 19. Mol Biol Cell. 2005, 16 (9): 4280-93. 10.1091/mbc.E05-02-0112.PubMedCentralCrossRefPubMed Stone MR, O'Neill A, Catino D, Bloch RJ: Specific interaction of the actin-binding domain of dystrophin with intermediate filaments containing keratin 19. Mol Biol Cell. 2005, 16 (9): 4280-93. 10.1091/mbc.E05-02-0112.PubMedCentralCrossRefPubMed
13.
go back to reference Lussier M, Filion M, Compton JG, Nadeau JH, Lapointe L, Royal A: The mouse keratin 19-encoding gene: sequence, structure and chromosomal assignment. Gene. 1990, 95 (2): 203-213. 10.1016/0378-1119(90)90363-V.CrossRefPubMed Lussier M, Filion M, Compton JG, Nadeau JH, Lapointe L, Royal A: The mouse keratin 19-encoding gene: sequence, structure and chromosomal assignment. Gene. 1990, 95 (2): 203-213. 10.1016/0378-1119(90)90363-V.CrossRefPubMed
14.
go back to reference Birchmeier W, Hülsken J, Behrens J: E-cadherin as an invasion suppressor. Ciba Found Symp. 1995, 189: 124-36. discussion 136–41, 174–176PubMed Birchmeier W, Hülsken J, Behrens J: E-cadherin as an invasion suppressor. Ciba Found Symp. 1995, 189: 124-36. discussion 136–41, 174–176PubMed
15.
go back to reference Chan JKC: Strict criteria should be applied in the diagnosis of encapsulated follicular variant of papillary thyroid carcinoma. Am J Clin Pathol. 2002, 117: 16-18. 10.1309/P7QL-16KQ-QLF4-XW0M.CrossRefPubMed Chan JKC: Strict criteria should be applied in the diagnosis of encapsulated follicular variant of papillary thyroid carcinoma. Am J Clin Pathol. 2002, 117: 16-18. 10.1309/P7QL-16KQ-QLF4-XW0M.CrossRefPubMed
16.
go back to reference LiVolsi VA, Baloch ZW: Follicular neoplasms of the thyroid: view, biases, and experiences. Adv Anat Pathol. 2004, 11: 279-287. 10.1097/01.pap.0000138143.34505.02.CrossRefPubMed LiVolsi VA, Baloch ZW: Follicular neoplasms of the thyroid: view, biases, and experiences. Adv Anat Pathol. 2004, 11: 279-287. 10.1097/01.pap.0000138143.34505.02.CrossRefPubMed
17.
go back to reference Lanier LL, Testi R, Bindl J, Phillips JH: Identity of Leu-19 (CD56) leukocyte differentiation antigen and neural cell adhesion molecule. J Exp Med. 1989, 169: 2233-10.1084/jem.169.6.2233.CrossRefPubMed Lanier LL, Testi R, Bindl J, Phillips JH: Identity of Leu-19 (CD56) leukocyte differentiation antigen and neural cell adhesion molecule. J Exp Med. 1989, 169: 2233-10.1084/jem.169.6.2233.CrossRefPubMed
18.
go back to reference Owens GC, Orr EA, Kleinschmidt DeMasters BK, Muschel RJ, Berens ME, Kruse CA: Overexpression of a transmembrane isoform of neural cell adhesion molecule alters the invasiveness of rat CNS-1 glioma. Cancer Res. 1998, 58: 2020-2028.PubMed Owens GC, Orr EA, Kleinschmidt DeMasters BK, Muschel RJ, Berens ME, Kruse CA: Overexpression of a transmembrane isoform of neural cell adhesion molecule alters the invasiveness of rat CNS-1 glioma. Cancer Res. 1998, 58: 2020-2028.PubMed
19.
go back to reference Rutishauser U, Acheson A, Hall AK, Mann DM, Sunshine J: The neural cell adhesion molecule (NCAM) as a regulator of cell-cell interactions. Science. 1988, 240: 53-57. 10.1126/science.3281256.CrossRefPubMed Rutishauser U, Acheson A, Hall AK, Mann DM, Sunshine J: The neural cell adhesion molecule (NCAM) as a regulator of cell-cell interactions. Science. 1988, 240: 53-57. 10.1126/science.3281256.CrossRefPubMed
20.
go back to reference Gratsa A, Rooprai HK, Rogers JP, Martin KK, Pilkengton GJ: Correlation of expression of NCAM and GD3 ganglioside to motile behaviour in neuroplastic glia. Anticancer Res. 1997, 17: 4111-4117.PubMed Gratsa A, Rooprai HK, Rogers JP, Martin KK, Pilkengton GJ: Correlation of expression of NCAM and GD3 ganglioside to motile behaviour in neuroplastic glia. Anticancer Res. 1997, 17: 4111-4117.PubMed
21.
go back to reference Prag S, Lepekhin EA, Kolkova K, Hartmann-Petersen R, Kawa A, Walmod PS, Belman V, Gallagher HC, Berezin V, Bock E, Pedersen N: NCAM regulates cell motility. Journal of Cell Science. 2002, 115: 283-292.PubMed Prag S, Lepekhin EA, Kolkova K, Hartmann-Petersen R, Kawa A, Walmod PS, Belman V, Gallagher HC, Berezin V, Bock E, Pedersen N: NCAM regulates cell motility. Journal of Cell Science. 2002, 115: 283-292.PubMed
22.
go back to reference Fogar P, Basso D, Pasquali C, De Paoli M, Sperti C, Roveroni G, Pedrazzoli S, Plebani M: Neural cell adhesion molecules (N-CAM) in gastrointestinal neoplasias. Anticancer Res. 1997, 17: 1227-1230.PubMed Fogar P, Basso D, Pasquali C, De Paoli M, Sperti C, Roveroni G, Pedrazzoli S, Plebani M: Neural cell adhesion molecules (N-CAM) in gastrointestinal neoplasias. Anticancer Res. 1997, 17: 1227-1230.PubMed
23.
go back to reference Zeromski J, Dworacki G, Jenek J, Niemir Z, Jezewska E, Jenek R, Biczysko M: Protein and mRNA expression of CD56/NCAM on follicular epithelial cells of the human thyroid. Int J Immunopathol Pharmacol. 1999, 12: 23-30.PubMed Zeromski J, Dworacki G, Jenek J, Niemir Z, Jezewska E, Jenek R, Biczysko M: Protein and mRNA expression of CD56/NCAM on follicular epithelial cells of the human thyroid. Int J Immunopathol Pharmacol. 1999, 12: 23-30.PubMed
24.
go back to reference Zeromski J, Lawniczak M, Galbas K, Jenek R, Golusinnski P: Expression of CD56/N-CAM antigen and some other adhesion molecules in various human endocrine glands. Folia Histoc Cytobiol. 1998, 36: 119-125. Zeromski J, Lawniczak M, Galbas K, Jenek R, Golusinnski P: Expression of CD56/N-CAM antigen and some other adhesion molecules in various human endocrine glands. Folia Histoc Cytobiol. 1998, 36: 119-125.
25.
go back to reference Xu XC, El-Naggar AK, Lotan R: Differential xxpression of galectin-1 and galectin-3 in thyroid tumors: potential diagnostic implications. Am J Pathol. 1995, 147: 815-822.PubMedCentralPubMed Xu XC, El-Naggar AK, Lotan R: Differential xxpression of galectin-1 and galectin-3 in thyroid tumors: potential diagnostic implications. Am J Pathol. 1995, 147: 815-822.PubMedCentralPubMed
26.
go back to reference Scarpino S, Di Napoli A, Melotti F, Talerico C, Cancrini A, Ruco L: Papillary carcinoma of the thyroid: low expression of NCAM (CD56) is associated with down regulation of VEGF-D production by tumor cells. J Pathol. 2007, 212 (4): 411-419. 10.1002/path.2183.CrossRefPubMed Scarpino S, Di Napoli A, Melotti F, Talerico C, Cancrini A, Ruco L: Papillary carcinoma of the thyroid: low expression of NCAM (CD56) is associated with down regulation of VEGF-D production by tumor cells. J Pathol. 2007, 212 (4): 411-419. 10.1002/path.2183.CrossRefPubMed
Metadata
Title
Application of CD56, P63 and CK19 immunohistochemistry in the diagnosis of papillary carcinoma of the thyroid
Authors
Dina El Demellawy
Ahmed Nasr
Salem Alowami
Publication date
01-12-2008
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2008
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/1746-1596-3-5

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