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The Diagnostic Value of Various Immunohistochemical Biomarkers in the Detection of Papillary and Follicular Thyroid Cancers: A Systematic Review and Metaanalysis

Document Type : Review Articles

Authors

1 Department of Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Pathology, Isfahan University of Medical Sciences, Isfahan, Iran.

3 Faculty of Management and Medical Information Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

4 Department of Epidemiology and Biostatistics, Isfahan University of Medical Sciences, Isfahan, Iran

5 School of Medicine, Shahrekord University of Medical Sciences, Isfahan, Iran

Abstract

Background: Thyroid neoplasia is the most common endocrine malignancy worldwide. Fine-needle aspiration biopsy of thyroid nodules has a low sensitivity in distinguishing between benign and malignant lesions. Evaluation of the rate of expression and diagnostic value of immunohistochemical biomarkers in differentiating between benign and malignant thyroid lesions and different types of malignant lesions is the main purpose of this study.
Methods: Sixty articles were reviewed in this systematic review and meta-analysis study. The rate of detection of various immunohistochemistry (IHC) biomarkers in several thyroid lesions was examined by meta-analysis. Specificity, sensitivity, positive and negative likelihood ratios, and confidence intervals (95% CI) were calculated for each marker. The accuracy of each test was evaluated by calculating the diagnostic odds ratio (DOR). ROC (receiver operating characteristic) analysis was performed for three markers.
Results: Sensitivity and specificity of CK-19, Gal-3, and carcinoembryonic antigen (CEA) for detection of thyroid malignancies were 81% and 73%, 82% and 81%, and 77% and 83 %, respectively. The combination of these three markers showed the sensitivity of 85%, specificity of 97%, and diagnostic odds ratio of 95.1. Additionally, uPAR, Sialyl Lewis X, MIB-1, and Hector Battifora mesothelial-1. (HBME-1) can effectively differentiate the follicular variant of papillary thyroid carcinoma (FVPTC) from follicular thyroid carcinoma (FTC) as they are significantly more common in FVPTCs (P<0.05).
Conclusion: We showed that CK-19, Gal-3, and CEA had an important and statistically significant role in differentiating between benign and malignant thyroid lesions. In addition, according to our results, urokinase-type plasminogen activator receptor (uPAR), Sialyl Lewis X, MIB-1, and HBME-1 can effectively differentiate FVPTC from FTC with acceptable sensitivity and specificity.

Highlights

Mitra Heidarpour (Google Scholar)

Keywords

References
  1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300. Erratum in: CA Cancer J Clin. 2011;61(2):133-4. doi: 10.3322/caac.20073. PMID: 20610543.
  2. Tuchscherer M, Otten W, Kanitz E, Gräbner M, Tuchscherer A, Bellmann O, Rehfeldt C, Metges CC. Effects of inadequate maternal dietary protein:carbohydrate ratios during pregnancy on offspring immunity in pigs. BMC Vet Res. 2012; 8:232. doi: 10.1186/1746-6148-8-232. PMID: 23190629; PMCID: PMC3527219.
  3. Peccin S, de Castsro JA, Furlanetto TW, Furtado AP, Brasil BA, Czepielewski MA. Ultrasonography: is it useful in the diagnosis of cancer in thyroid nodules? J Endocrinol Invest. 2002;25(1):39-43. doi: 10.1007/BF03343959. PMID: 11885575.
  4. Tomimori EK, Bisi H, Medeiros-Neto G, Camargo RYA de. Avaliação ultra-sonográfica dos nódulos tireóideos: comparação com exame citológico e histopatoló Arq Bras Endocrinol Metab [Internet]. 2004;48(1):105–13. doi: 10.1590/S0004-27302004000100012.
  5. Utiger RD. The multiplicity of thyroid nodules and carcinomas. N Engl J Med. 2005 Jun 9;352(23):2376-8. doi: 10.1056/NEJMp058061. PMID: 15944422.
  6. Schlumberger MJ. Papillary and follicular thyroid carcinoma. N Engl J Med. 1998; 338(5):297-306. doi: 10.1056/NEJM199801293380506. PMID: 9445411.
  7. LiVolsi VA, Baloch ZW. Follicular neoplasms of the thyroid: view, biases, and experiences. Adv Anat Pathol. 2004; 11(6):279-87. doi: 10.1097/01.pap.0000138143.34505.02. PMID: 15505528.
  8. Zeiger MA, Dackiw AP. Follicular thyroid lesions, elements that affect both diagnosis and prognosis. J Surg Oncol. 2005; 89(3):108-13. doi: 10.1002/jso.20186. PMID: 15719377.
  9. Barroeta JE, Baloch ZW, Lal P, Pasha TL, Zhang PJ, LiVolsi VA. Diagnostic value of differential expression of CK19, Galectin-3, HBME-1, ERK, RET, and p16 in benign and malignant follicular-derived lesions of the thyroid: an immunohistochemical tissue microarray analysis. Endocr Pathol. 2006; 17(3):225-34. doi: 10.1385/ep:17:3:225. PMID: 17308359.
  10. Saussez S, Glinoer D, Chantrain G, Pattou F, Carnaille B, André S, Gabius HJ, Laurent G. Serum galectin-1 and galectin-3 levels in benign and malignant nodular thyroid disease. Thyroid. 2008; 18(7):705-12. doi: 10.1089/thy.2007.0361. PMID: 18630998.
  11. Yoshii T, Inohara H, Takenaka Y, Honjo Y, Akahani S, Nomura T, Raz A, Kubo T. Galectin-3 maintains the transformed phenotype of thyroid papillary carcinoma cells. Int J Oncol. 2001; 18(4):787-92. doi: 10.3892/ijo.18.4.787. PMID: 11251175.
  12. Baloch ZW, Abraham S, Roberts S, LiVolsi VA. Differential expression of cytokeratins in follicular variant of papillary carcinoma: an immunohistochemical study and its diagnostic utility. Hum Pathol. 1999; 30(10):1166-71. doi: 10.1016/s0046-8177(99)90033-3. PMID: 10534163.
  13. Kato MA, Fahey TJ 3rd. Molecular markers in thyroid cancer diagnostics. Surg Clin North Am. 2009; 89(5):1139-55. doi: 10.1016/j.suc.2009.06.012. PMID: 19836489.
  14. Eszlinger M, Paschke R. Molecular fine-needle aspiration biopsy diagnosis of thyroid nodules by tumor specific mutations and gene expression patterns. Mol Cell Endocrinol. 2010; 322(1-2):29-37. doi: 10.1016/j.mce.2010.01.010. PMID: 20083161.
  15. Yuan L, Nasr C, Bena JF, Elsheikh TM. Hürthle cell-predominant thyroid fine needle aspiration cytology: A four risk-factor model highly accurate in excluding malignancy and predicting neoplasm. Diagn Cytopathol. 2022; 50(9):424-435. doi: 10.1002/dc.25000. PMID: 35674254; PMCID: PMC9543473.
  16. McKee S, Wu H, Wang X, Cramer H, Lin J, Chen S; Hürthle Cell Neoplasms Diagnosed by Fine Needle Aspiration Are Not Associated with an Increased Risk of Malignancy. Acta Cytologica. 2014; 58 (3): 235– doi: 10.1159/000361073.
  17. de Micco C, Savchenko V, Giorgi R, Sebag F, Henry JF. Utility of malignancy markers in fine-needle aspiration cytology of thyroid nodules: comparison of Hector Battifora mesothelial antigen-1, thyroid peroxidase and dipeptidyl aminopeptidase IV. Br J Cancer. 2008; 98(4):818-23. doi: 10.1038/sj.bjc.6604194. PMID: 18212751; PMCID: PMC2259194.
  18. Mijovic T, Gologan O, Rochon L, Hier M, Black MJ, Young J, Rivera J, Tamilia M, Payne RJ. Fine-needle aspiration biopsy of the thyroid: review of cytopathologic features predictive of malignancy. J Otolaryngol Head Neck Surg. 2009; 38(3):348-54. PMID: 19476767.
  19. Ivanova R, Soares P, Castro P, Sobrinho-Simões M. Diffuse (or multinodular) follicular variant of papillary thyroid carcinoma: a clinicopathologic and immunohistochemical analysis of ten cases of an aggressive form of differentiated thyroid carcinoma. Virchows Arch. 2002; 440(4):418-24. doi: 10.1007/s00428-001-0543-3. PMID: 11956824.
  20. Rossi ED, Raffaelli M, Minimo C, Mule A, Lombardi CP, Vecchio FM, Fadda G. Immunocytochemical evaluation of thyroid neoplasms on thin-layer smears from fine-needle aspiration biopsies. Cancer. 2005; 105(2):87-95. doi: 10.1002/cncr.21026. PMID: 15742329.
  21. 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(9269):1644-50. doi: 10.1016/s0140-6736(00)04817-0. PMID: 11425367.
  22. Nergård-Nilssen T, Hulme C. Developmental dyslexia in adults: behavioural manifestations and cognitive correlates. Dyslexia. 2014; 20(3):191-207. doi: 10.1002/dys.1477. PMID: 24842581.
  23. Collet JF, Hurbain I, Prengel C, Utzmann O, Scetbon F, Bernaudin JF, Fajac A. Galectin-3 immunodetection in follicular thyroid neoplasms: a prospective study on fine-needle aspiration samples. Br J Cancer. 2005; 93(10):1175-81. doi: 10.1038/sj.bjc.6602822. PMID: 16251880; PMCID: PMC2361502.
  24. Kim MJ, Kim HJ, Hong SJ, Shong YK, Gong G. Diagnostic utility of galectin-3 in aspirates of thyroid follicular lesions. Acta Cytol. 2006; 50(1):28-34. doi: 10.1159/000325891. PMID: 16514837.
  25. Carpi A, Naccarato AG, Iervasi G, Nicolini A, Bevilacqua G, Viacava P, Collecchi P, Lavra L, Marchetti C, Sciacchitano S, Bartolazzi A. Large needle aspiration biopsy and galectin-3 determination in selected thyroid nodules with indeterminate FNA-cytology. Br J Cancer. 2006; 95(2):204-9. doi: 10.1038/sj.bjc.6603232. PMID: 16804521; PMCID: PMC2360621.
  26. Giovanella L, Crippa S, Cariani L. Serum calcitonin-negative medullary thyroid carcinoma: role of CgA and CEA as complementary markers. Int J Biol Markers. 2008; 23(2):129-31. doi: 10.1177/172460080802300212. PMID: 18629788.
  27. Jain R, Fischer S, Serra S, Chetty R. The use of Cytokeratin 19 (CK19) immunohistochemistry in lesions of the pancreas, gastrointestinal tract, and liver. Appl Immunohistochem Mol Morphol. 2010; 18(1):9-15. doi: 10.1097/PAI.0b013e3181ad36ea. PMID: 19956064.
  28. Ito Y, Yoshida H, Tomoda C, Uruno T, Miya A, Kobayashi K, Matsuzuka F, Kakudo K, Kuma K, Miyauchi A. S100A4 expression is an early event of papillary carcinoma of the thyroid. Oncology. 2004;67(5-6):397-402. doi: 10.1159/000082924. PMID: 15713996.
  29. Ding Z, Ke R, Zhang Y, Fan Y, Fan J. FOXE1 inhibits cell proliferation, migration and invasion of papillary thyroid cancer by regulating PDGFA. Mol Cell Endocrinol. 2019; 493:110420. Mol Cell Endocrinol. 2022; 549:111640. doi: 10.1016/j.mce.2019.03.010. PMID: 31129275.
  30. Mond M, Bullock M, Yao Y, Clifton-Bligh RJ, Gilfillan C, Fuller PJ. Somatic Mutations of FOXE1 in Papillary Thyroid Cancer. Thyroid. 2015; 25(8):904-10. doi: 10.1089/thy.2015.0030. PMID: 25950909.
  31. Bartolazzi A, Orlandi F, Saggiorato E, Volante M, Arecco F, Rossetto R and et al; Italian Thyroid Cancer Study Group (ITCSG). Galectin-3-expression analysis in the surgical selection of follicular thyroid nodules with indeterminate fine-needle aspiration cytology: a prospective multicentre study. Lancet Oncol. 2008; 9(6):543-9. doi: 10.1016/S1470-2045(08)70132-3. PMID: 18495537.
  32. Pennelli G, Mian C, Pelizzo MR, Naccamulli D, Piotto A, Girelli ME, and et al. Galectin-3 cytotest in thyroid follicular neoplasia: a prospective, monoinstitutional study. Acta Cytol. 2009; 53(5):533-9. doi: 10.1159/000325381. PMID: 19798881.
  33. Bonzanini M, Amadori PL, Sagramoso C, Dalla Palma P. Expression of cytokeratin 19 and protein p63 in fine needle aspiration biopsy of papillary thyroid carcinoma. Acta Cytol. 2008; 52(5):541-8. doi: 10.1159/000325595. PMID: 18833815.
  34. Mase T, Funahashi H, Koshikawa T, Imai T, Nara Y, Tanaka Y, Nakao A. HBME-1 immunostaining in thyroid tumors especially in follicular neoplasm. Endocr J. 2003; 50(2):173-7. doi: 10.1507/endocrj.50.173. PMID: 12803237.
  35. Ozolins A, Narbuts Z, Strumfa I, Volanska G, Gardovskis J. Diagnostic utility of immunohistochemical panel in various thyroid pathologies. Langenbecks Arch Surg. 2010; 395(7):885-91. doi: 10.1007/s00423-010-0690-6. PMID: 20640858.
  36. Busnardo B, Girelli ME, Simioni N, Nacamulli D, Busetto E. Nonparallel patterns of calcitonin and carcinoembryonic antigen levels in the follow-up of medullary thyroid carcinoma. Cancer. 1984; 53(2):278-85. doi: 10.1002/1097-0142(19840115)53:2<278:aid-cncr2820530216>3.0.co;2-z. PMID: 6690009.
  37. Baquero P, Sánchez-Hernández I, Jiménez-Mora E, Orgaz JL, Jiménez B, Chiloeches A. (V600E) BRAF promotes invasiveness of thyroid cancer cells by decreasing E-cadherin expression through a Snail-dependent mechanism. Cancer Lett. 2013; 335(1):232-41. doi: 10.1016/j.canlet.2013.02.033. PMID: 23435375.
  38. McFadden DG, Vernon A, Santiago PM, Martinez-McFaline R, Bhutkar A, Crowley DM, McMahon M, Sadow PM, Jacks T. p53 constrains progression to anaplastic thyroid carcinoma in a Braf-mutant mouse model of papillary thyroid cancer. Proc Natl Acad Sci U S A. 2014; 111(16): E1600-9. doi: 10.1073/pnas.1404357111. PMID: 24711431; PMCID: PMC4000830.
  39. Torregrossa L, Faviana P, Filice ME, Materazzi G, Miccoli P, Vitti P, Fontanini G, Melillo RM, Santoro M, Basolo F. CXC chemokine receptor 4 immunodetection in the follicular variant of papillary thyroid carcinoma: comparison to galectin-3 and hector battifora mesothelial cell-1. Thyroid. 2010; 20(5):495-504. doi: 10.1089/thy.2009.0282. PMID: 20450430.
  40. Schmitt AC, Cohen C, Siddiqui MT. Paired box gene 8, HBME-1, and cytokeratin 19 expression in preoperative fine-needle aspiration of papillary thyroid carcinoma: diagnostic utility. Cancer Cytopathol. 2010; 118(4):196-202. doi: 10.1002/cncy.20082. PMID: 20731005.
Journal of Health Sciences & Surveillance System
Volume 12, Issue 2
April 2024
Pages 125-133
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