Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2008, 152(1):53-59 | DOI: 10.5507/bp.2008.008

POTENTIAL DIAGNOSTIC MARKERS IN NODULAR LESIONS OF THE THYROID GLAND: AN IMMUNOHISTOCHEMICAL STUDY

Marie Rydlovaa, Marie Ludvikovab,c, Ivana Stankovac
a Department of Pathology, Municipal Hospital, Ostrava, Czech Republic
b Institute of Biology, Charles University, Medical Faculty, Plzen, Czech Republic
c Department of Pathology, 1st Medical Faculty Hospital, Prague, Czech Republic

Aims: The differential diagnosis of thyroid nodules in routine practice can be problemmatic for both pathologists and clinicians. Effective treatment requires a determination of the biological nature of the lesions. For this reason, ancilliary diagnostic markers along with histological examination of the nodules may be useful. The objective of this study was to evaluate the diagnostic usefulness of novel markers in the diagnosis of hyperplastic and neoplastic nodules.

Methods: Forty eight thyroid lesions forming four diagnostic groups including adenomatous goiters (AS), follicular adenomas (FA), follicular (FC) and papillary carcinomas (PC) were examined using standard immunohistochemical methods. Monoclonal antibodies against galectin-3, matrix metalloproteinases (MMPs) -2 and -7 and endothelial markers CD31 and CD105 were used.

Results: The cytoplasmatic expression of galectin-3 was positive in all cases of papillary carcinoma. Moreover, statistically significant differences between fused groups of benign (AS and FA) and malignant lesions (FC and PC) were found Fischer's exact test (p = 0.0001). No significant differences in cytoplasmic expression of MMPs -2 and -7 and in vascular density assessed by using of both endothelial markers between benign lesions and malignant tumors were revealed.

Conclusions: Galectin-3 appears to be a useful marker in the diagnosis of papillary carcinoma only. The matrix metalloproteinases-2 and -7 are not helpful in distinguishing hyperplastic and neoplastic thyroid nodules. Endothelial markers do not appear to be suitable for thyroid differential diagnosis. A panel of antibodies in the differential diagnosis of thyroid nodular lesions would seem most suitable and further studies with larger sets of patients are awaited.

Keywords: Thyroid gland nodule, Adenoma, Carcinoma, Diagnostic marker, Galectin-3, Angiogenesis, Matrix metalloproteinases, Immunohistochemistry

Received: February 15, 2008; Accepted: March 21, 2008; Published: June 1, 2008  Show citation

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Rydlova, M., Ludvikova, M., & Stankova, I. (2008). POTENTIAL DIAGNOSTIC MARKERS IN NODULAR LESIONS OF THE THYROID GLAND: AN IMMUNOHISTOCHEMICAL STUDY. Biomedical papers152(1), 53-59. doi: 10.5507/bp.2008.008
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References

  1. Rosai J, Carcangiu ML, DeLellis RA. Tumors of thyroid gland. In Rosai J, Sobin H: Atlas of tumor pathology, 3rd Series, Fascicle 5. Washington, DC: A.F.I.P., 1992.
  2. Cho Mar K, Eimoto T, Tateyama H, Arai Y, Fujiyoshi Y, Hamaguchi M. Expression of matrix metalloproteinases in benigh and malignant follicular thyroid lesions. Histopathology 2006; 48:286-94. Go to original source... Go to PubMed...
  3. Williams ED. Two proposals regarding the terminology of thyroid tumors. Int J Surg Pathol 2000; 8:181-3. Go to original source... Go to PubMed...
  4. De Matos PS, Ferreira AP, de Oliveira Facuri F, Assumpcao LVM, 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. Go to original source... Go to PubMed...
  5. Stephenson TJ. Papillary carcinoma of the thyroid: a tumour still with no benign neoplastic counterpart. Histopathology 2001; 39:536-38. Go to original source... Go to PubMed...
  6. Kholova I, Ryska A, Ludvikova M, Cap J. Thyroid peroxidase in the diff erential diagnosis of thyroid gland lesions. A marker of biological behavior or diff erentiation? Cesk Pathol 2004; 40(1):18-21 (in Czech).
  7. Kholova I, Ludvikova M, Ryska A, Hanzelkova Z, Cap J, Pecen L et. al. Immunohistochemical detection of dipeptidylpeptidase IV (CD26) in thyroid neoplasia using biotinylated tyramine amplifi cation. Neoplasma 2003; 50(3):159-164. Go to PubMed...
  8. Kholova I, Ryska A, Ludvikova M, Cap J, Pecen L. Dipeptidyl peptidase IV expression in thyroid cytology: retrospective histologically confi rmed study. Cytopathology 2003; 14(1):27-31. Go to original source... Go to PubMed...
  9. Kholova I, Ludvikova M, Ryska A, Topolcan O, Pikner R, Pecen L et. al. Diagnostic role of markers dipeptidyl peptidase IV and thyroid peroxidase in thyroid tumors. Anticancer Res 2003; 23(2A):871-75. Go to PubMed...
  10. Kholova I, Ryska A, Ludvikova M, Pecen L, Cap J. Dipeptidyl peptidase IV (DPP IV, CD 26): a tumor marker in cytologic and histopathologic diagnosis of lesions of the thyroid gland. Čas Lék Česk 2003; 142(3):167-71 (in Czech). Go to PubMed...
  11. Beesley MF, McLaren KM. Cytokeratin 19 and galectin-3 immunohistochemistry in the diff erential diagnosis of solitary thyroid nodules. Histopathology 2002; 41:236-43. Go to original source... Go to PubMed...
  12. Laco J, Ryska A. The use of immunohistochemistry in the differential diagnosis of thyroid gland tumors with follicular growth pattern. Cesk Patol. 2006;42(3):120-4 (in Czech). Go to PubMed...
  13. Ito Y, Yoshida H, Tomoda C, Miya A, Kobayashi K, Matsuzuka F, et al. Galectin-3 expression in follicular tumours: an immunohistochemical study of its use as a marker of follicular carcinoma. Patology 2005; 37:296-8. Go to original source... Go to PubMed...
  14. Temmim L, Ebraheem AK, Baker H, Sinowatz F: Cyclin D1 protein expression in human thyroid gland and thyroid cancer. Anat Histol Embryol 2005; ISSN 0340-2096. Go to original source...
  15. Lantsov D, Meirmanov S, Nakashima M, Kondo H, Saenko V, Naruke Y, et al. Cyclin D1 overexpression in thyroid papillary microcarcinoma: its association with tumour size and aberrant betacatenin expression. Histopathology 2005; 47:247-56. Go to original source... Go to PubMed...
  16. Ludvikova M, Ryska A, Hovorkova E, Pikner R. Role of proliferative marker MIB-1 in diagnosis and prognosis of thyroid gland tumors. Česk Patol 2002; 38(1):4-10 (in Czech).
  17. Pikner R, Ludvikova M, Ryska A, Kholova I, Holubec L Jr, Topolcan O, et al. TPS, thymidine kinase, VEGF and endostatin in cytosol of thyroid tissue samples. Anticancer Res 2005; 25:1517- 22.
  18. Unger P., Ewart M, Wang BY, Gan L, Kohtz SD, Burstein DE: Expression of p63 in papillary thyroid carcinoma and in Hashimoto´s thyroiditis: A pathobiologic link? Hum Pathol 2003; 34:764-9. Go to original source... Go to PubMed...
  19. Ludvikova M, Holubec LJr, Topolcan O. Proliferative markers in diagnosis and prognosis of thyroid tumors: a comparative study of MIB-1 and topoisomerase II- immunostaining. Anticancer Res 2005; 25:1835-40.
  20. Ludvíkova M, Topolčan O, Kholova I, Rydlova M, Holubec L: Can tumor markers be helpful in thyroid nodules diagnosis? Plzeň. Lék. Sborn. 2005; Suppl.80:71-4.
  21. Weidner N, Semple JP, Welch WR, Folkman J. Tumour angiogenesis and metastasis-correlation in invasive breast carcinoma. N Engl J Med 1991; 324:1-8. Go to original source... Go to PubMed...
  22. Gaff ney RL, Carney JA, Sebo TH, Erickson LA, Volante M, Papotti M, et al. Galectin-3 expression in hyalinizing trabecular tumors of the thyroid gland. Am J Surg Pathol 2003; 27:494-8. Go to original source... Go to PubMed...
  23. Mehrotra P, Okpokam A, Bouhaidar R, Johnson SJ, Wilson JA, Davies BR, et al. Galectin-3 does not reliably distinguish benign from malignant thyroid neoplasms. Histopathology 2004; 45:493- 500. Go to original source... Go to PubMed...
  24. De Micco C, Ruf J, Chrestian MA, Gros N, Henry JF, Carayon P. Immunohistochemical study of thyroid peroxidase in normal, hyperplastic, and neoplastic human thyroid tissues. Cancer 1991; 67:3036-41. Go to original source... Go to PubMed...
  25. De Micco C. Thyroid cytology: evaluation and perspectives. Annals of Endocrinology Paris. 1993; 54:258-63.
  26. De Micco C, Zoro P, Henry JF. Malignancy markers in the cytodiagnosis of thyroid nodules. Thyroid peroxidase. Annals of Pathology 1994; 14:378-83.
  27. De Micco C, Vasko V, Garcia S, Zoro P, Denizot A, Henry JF. Fine-needle aspiration of thyroid follicular neoplasm: Diagnostic use of thyroid peroxidase immunocytochemistry with monoclonal antibody 47. Surgery 1994; 116:1031-35. Go to PubMed...
  28. Umeki K, Tanaka T, Yamamoto I, Aratake Y, Kotani T, Sakamoto F, et al. Diff erential expression of dipeptidylpeptidase IV (CD26) and thyroid peroxidase in neoplastic thyroid tissues. Endocr J 1996; 43:53-60. Go to original source... Go to PubMed...
  29. Cvejic D, Savin S, Petrovic I, Tatic S, Krkovic K, Havelka M. Galectin-3 expression in papillary microcarcinoma of the thyroid. Histopathology 2005; 47:209-14. Go to original source... Go to PubMed...
  30. Buttery R, Monaghan H, Salter CM, Sethi T. Galectin-3: diff erential expression between small-cell and non-small-cell lung cancer. Histopathology 2004; 44:339-44. Go to original source... Go to PubMed...
  31. Orlandi F, Saggiorato E, Pivano G, Puligheddu B, Termine B, Cappia S, et al. Galectin-3 is a presurgical marker of human thyroid carcinoma. Cancer Research 1998; 58:3015-20. Go to PubMed...
  32. Cvejic D, Savin S, Golubovic S, Paunovic I, Tatic S, Havelka M. Galectin-3 and carcinoembryonic antigen expression in medullary thyroid carcinoma: possible relation to tumour progression. Histopathology 2000; 37:530-35. Go to original source... Go to PubMed...
  33. Curran S and Murray GI. Matrix metalloproteinases in tumour invasion and metastasis. J Pathol 1999; 189:300-8. Go to original source... Go to PubMed...
  34. Manello F. Natural bio-drugs as matrix metalloproteinase inhibitors: New perspectives on the horizon? Recent Patents on Anti- Cancer Drug Discovery 2006; 1:91-103. Go to original source... Go to PubMed...
  35. Nelson AR, Fingleton B, Rothenberg ML, Matrisian LM. Matrix metalloproteinases: Biologic activity an clinical implications. J Clin Oncol 2000; 18:1135-49. Go to original source... Go to PubMed...
  36. Takahashi E, Tateyama H, Akatsu H, Fukai I, Yamakawa Y. Expression of matrix metalloproteinases 2 and 7 in tumor cells correlates with the World Health Organisation classifi cation subtype and clinical stage of thymic epithelial tumors. Hum Pathol 2003; 34:1253-8. Go to original source... Go to PubMed...
  37. Aribas A. Matrix metalloproteases and tumor invasion. NEJM 2005; 352:2020-1. Go to original source... Go to PubMed...
  38. Nguyen N, Kuliopulos A, Graham RA, Covic L. Tumor-derived Cyr61 (CCN1) promotes stromal matrix metalloproteinase-1 production and protease-activated receptor 1-dependent migration of breast cancer cells. Cancer Res 2006; 66:2658-65. Go to original source... Go to PubMed...
  39. Nagel H, Laskawi R, Wahlers A, Hemmerlein B. Expression of matrix metalloproteinases MMP-2, MMP-9 and their tissue inhibitors TIMP-1, -2, and -3 in benign and malignant tumours of the salivary gland. Histopathology 2004; 44:222-31. Go to original source... Go to PubMed...
  40. Tien YW, Lee PH, Hu RH, Hsu SM, Chang KJ. The role of gelatinase in hepatic metastasis of colorectal cancer. Clin Cancer Res 2003; 9:4891-96.
  41. Ishida H, Murata N, Tada M, Okada N, Hashimoto D, Kubota S, et al. Determining the levels of matrix metalloproteinases-9 in portal and peripheral blood is useful for predicting liver metastases of colorectal cancer. Jpn J Clin Oncol 2003; 33:186-91. Go to original source... Go to PubMed...
  42. Curran S, Dundas SR, Buxton J, Leeman MF, Ramsay R, Murray GI. Matrix metalloproteinase/tissue inhibitors of matrix metalloproteinase phenotype identifi es poor prognosis colorectal cancers. Clin Cancer Res 2004; 10:8229-34. Go to original source... Go to PubMed...
  43. Pesta M, Holubec L Jr, Topolcan O, Cerna M, Rupert K, Holubec LS, et al. Quantitative estimation of matrix metalloproteinases 2 and 7 (MMP-2, MMP-7) and tissue inhibitors of matrix metalloproteinases 1 and 2 (TIMP-1, TIMP-2) in colorectal carcinoma tissue samples. Anticancer Res 2005; 25:3387-91.
  44. Waas ET, Wobbes T, Ruers T, Lomme RM, Hendriks T. Circulating gelatinases and tissue inhibitor of metalloproteinase-1 in colorectal cancer metastatis liver disease. Eur J Surg Oncol 2006; 32:756- 63. Go to original source... Go to PubMed...
  45. Massi D, Franchi A, Ketabchi S, Paglierani M, Pimpinelli N, Santucci M. Expression and prognostic signifi cance of matrix metalloproteinases and their tissue inhibitors in primary neuroendocrine carcinoma of the skin. Hum Pathol 2003; 34:80-8. Go to original source... Go to PubMed...
  46. Holubec L, sen et al. Colorectal carcinoma. Praha: Grada Publishing 2004; ISBN 80-247-0636-9:25-27.
  47. Stetler-Stevenson WG. Matrix metalloproteinases in angiogenesis: Moving target for therapeutic intervention. J Clin Invest 1999; 103:1237-41. Go to original source... Go to PubMed...
  48. Nabeshima K, Inoue, T, Shimao Y, Sameshima T. Matrix metalloproteinases in tumor invasion: Role for cell migration. Pathology International 2002; 52:255-64. Go to original source... Go to PubMed...
  49. Campo E, Merino MJ, Liotta L. Distribution of the 72-kD type IV colagenase in nonneoplastic and neoplastic thyroid tissue. Hum Pathol 1992; 23:1395-1401. Go to original source... Go to PubMed...
  50. Maeta H, Ohgi S, Terada T. Protein expression of matrix metalloproteinases 2 and 9 and tissue inhibitors of metalloproteinase 1 and 2 in papillary thyroid carcinomas. Virchows Arch 2001; 438:121- 128. Go to original source... Go to PubMed...
  51. Saad RS, Liu YL, Nathan G, Celebrezze J, Medich D, Silverman JF. Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer. Mod Pathol 2004; 17:197- 203. Go to original source... Go to PubMed...
  52. De Lisser HM, Christofi dou-Solomidou M, Strieter RM, Burdick MD, Robinson CS, Wexler RS, et al. Involvement of endothelial PECAM-1/CD31 in angiogenesis. Am J Pathol 1997; 151:671-77.
  53. Minhajat R, Mori D, Yamasaki F, Sugita Y, Satoh T,Tokunaga. Organ-specifi c endoglin (CD105) expression in the angiogenesis of human cancers. Pathol Int 2006; 56:717-23Erdem O, Taskiran C, Onan MA, Erdem M, Guner H, Ataoglu O. CD105 expression is an independent predictor of survival in patients with endometrial cancer. Gynecol Oncol 2006; 103:1007-11. Go to original source... Go to PubMed...
  54. Kondo S, Scheef EA, Sheibani N, Sorenson CM. PECAM-1 isoform- specifi c regulation of kidney endothelial cell migration and capillary morphogenesis. Am J Physiol Cell Physiol 2007; 292: C2070-83. Go to original source... Go to PubMed...
  55. Polverini PJ. Cellular adhesion molecules. Am J Pathol 1996; 148:1023-1029.
  56. Fonsatti E, Maio M. Highlights on endoglin (CD105): from basic fi ndings towards clinical applications in human cancer. J Transl Med 2004; 2:18. Go to original source... Go to PubMed...
  57. Mayers MM, Seshadri R, Raymond W, McCaul K, Horsfall DJ: Tumor microvascularity has no independent prognostic signifi cance for breast cancer. Pathology 1998; 30:105-10. Go to original source... Go to PubMed...
  58. Jugenburg M, Kovacs K, Stefaneanu L, Scheithauer BW. Vasculature in nontumorous hypophyses, pituitary adenomas, and carcinomas: A quantitative morphologic study. Endocr Pathol 1995; 6:115- 124. Go to original source... Go to PubMed...
  59. Liu Q, Djuricin G, Staren ED, Gattuso P, Gould VE, Shen J, et al. Tumor angiogenesis in pheochromocytomas and paragangliomas. Surgery 1996; 150:938-43. Go to original source... Go to PubMed...
  60. Ishiwata T, Iino Y, Takei H, Oyama T. Morishita Y. Tumor angiogenesis as an independent prognostic indicator in human papillary thyroid carcinoma. Oncol Rep 1998; 5:1343-8. Go to original source... Go to PubMed...
  61. Lennard CM, Patel A, Wilson J, Reinhardt B, Tuman C, Fenton C, et al. Intensity of vascular endothelial growth factor expression is associated with increased risk of recurrence and decreased diseasefree survival in papillary thyroid cancer. Surgery 2001; 129:552-8. Go to original source... Go to PubMed...
  62. Fontanini G, Vignati S, Pacini F, Pollina L, Basolo F: Microvessel count: an indicator of poor outcome in medullary thyroid carcinoma but not in other types of thyroid carcinoma. Mod Pathol 1996; 9:636-41.
  63. Ryska A, Ludvikova M, Klaboch J, Laco J, Kholova I, Topočan O. Angiogenesis in thyroid gland tumors. Biomarkers and Environment 2002; 5:24-31.
  64. Kuzu I, Bicknell R, Harris AL, Jones M, Gatter KC, Mason DY. Heterogenity of vascular endothelial cells with relevance to diagnosis of vascular tumors. J Clin Pathol 1992; 45:143-8. Go to original source... Go to PubMed...
  65. Erdem O, Taskiran C, Onan MA, Erdem M, Guner H, Ataoglu O. CD105 expression is an independent predictor of survival in patients with endometrial cancer. Gynecol Oncol 2006; 103:1007- 11. Go to original source... Go to PubMed...
  66. Wikstrom P, Lissbrant IF, Stattin P, Egevald L, Bergh A. Endoglin (CD105) is expressed on immature blood vessels and is a marker for survival in prostate cancer. Prostate 2002; 51:268-75. Go to original source... Go to PubMed...
  67. Ranefall P, Wester K, Busch Ch, Malmström PU, Bengtsson E: Automatic quantifi cation of microvessels using unsupervised image analysis. Anal Cell Pathol 1998; 17:83-92. Go to original source... Go to PubMed...
  68. Nikiteas NI, Tzanakis N, Theodoropoulos G, Atsaves V, Christoni Z, Karakitsos P, Lazaris AC, Papachristodoulou A, Klonaris C, Gazouli M. Vascular endothelial growth factor and endoglin (CD- 105) in gastric cancer. Gastric Cancer 2007; 10:12-7. Go to original source... Go to PubMed...
  69. Erdem O, Erdem M, Erdem A, Memis L, Akyol G. Expression of vascular endothelial growth factor and assessment of microvascular density with CD 34 and endoglin in proliferative endometrium, endometrial hyperplasia, and endometrial carcinoma. Int J Gynecol Cancer 2007; 17:1327-32. Go to original source... Go to PubMed...