Top

Published in:

01-07-2005 | Original Article

Global DNA methylation evaluation: potential complementary marker in differential diagnosis of thyroid neoplasia

Authors: Bogdan Galusca, Jean Marc Dumollard, Sandrine Lassandre, Alain Niveleau, Jean Michel Prades, Bruno Estour, Michel Peoc’h

Published in: Virchows Archiv | Issue 1/2005

Abstract

The implications of global DNA hypomethylation were recently reported in several models of tumorigenesis. Little is known about this epigenetic event in thyroid neoplasia. The study aimed to evaluate the status of global DNA methylation in several types of thyroid tumors using a monoclonal antibody specific for 5-methylcytidine (5-mc) and to define the diagnosis potential of this marker. 5-mc immunostaining scores were calculated in 17 papillary thyroid carcinomas (PTC), 6 follicular thyroid carcinomas (FTC), 16 follicular adenomas (FA), 19 nodular goiters (NG) and ten Hürthle cells adenomas (HCA). The expression of galectin-3 was also evaluated. Computerized image analysis showed a significant lower level of 5-mc immunostaining in thyroid carcinoma when compared with benign tumors or adjacent normal thyroid parenchyma (P<0.0001). Overall, 5-mc accuracy to distinguish malign from benign thyroid tumors was similar to that of galectin-3 (89% versus 87%, P>0.05). The combination of 5-mc with galectin-3 led to an excellent accuracy level of 96%. Among follicular neoplasia 5-mc accuracy to differentiate malign tumors trends to be higher than galectin-3 one (90% versus 66%, P=0.06). These data stress the necessity of epigenetic events evaluation among thyroid nodules and propose global DNA methylation assessment as a potential diagnostic tool to combine with other valuable markers.

Aratake Y, Umeki K, Kiyoyama K, Hinoura Y, Sato S, Ohno A, Kuribayashi T, Hirai K, Nabeshima K, Kotani T (2002) Diagnostic utility of galectin-3 and CD26/DPPIV as preoperative diagnostic markers for thyroid nodules. Diagn Cytopathol 26:366–372CrossRefPubMed

Baloch ZW, Fleisher S, LiVolsi VA, Gupta PK (2002) Diagnosis of “follicular neoplasm”: a gray zone in thyroid fine-needle aspiration cytology. Diagn Cytopathol 26:41–44CrossRefPubMed

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 (2001) Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions. Lancet 357:1644–1650CrossRefPubMed

Bartolazzi A, Papotti M, Orlandi F (2003) Methodological considerations regarding the use of galectin-3 expression analysis in preoperative evaluation of thyroid nodules. J Clin Endocrinol Metab 88:950; author reply 950–951CrossRefPubMed

Beesley MF, McLaren KM (2002) Cytokeratin 19 and galectin-3 immunohistochemistry in the differential diagnosis of solitary thyroid nodules. Histopathology 41:236–243CrossRefPubMed

Bernet VJ, Anderson J, Vaishnav Y, Solomon B, Adair CF, Saji M, Burman KD, Burch HB, Ringel MD (2002) Determination of galectin-3 messenger ribonucleic Acid overexpression in papillary thyroid cancer by quantitative reverse transcription-polymerase chain reaction. J Clin Endocrinol Metab 87:4792–4796CrossRefPubMed

Boltze C, Schneider-Stock R, Quednow C, Hinze R, Mawrin C, Hribaschek A, Roessner A, Hoang-Vu C (2003) Silencing of the maspin gene by promoter hypermethylation in thyroid cancer. Int J Mol Med 12:479–484PubMed

Boltze C, Zack S, Quednow C, Bettge S, Roessner A, Schneider-Stock R (2003) Hypermethylation of the CDKN2/p16INK4A promotor in thyroid carcinogenesis. Pathol Res Pract 199:399–404PubMed

Buchs AE, Zehavi S, Sher O, Yeheskely E, Muggia-Sulam M, Sherman Y, Rapoport MJ (2003) Heparanase, galectin-3, and tissue factor mRNA are expressed in benign neoplasms of the thyroid. Endocrine 22:81–84CrossRefPubMed

10.

Casey MB, Lohse CM, Lloyd RV (2003) Distinction between papillary thyroid hyperplasia and papillary thyroid carcinoma by immunohistochemical staining for cytokeratin 19, galectin-3, and HBME-[1] Endocr Pathol 14:55–60CrossRefPubMed

11.

Chow LS, Gharib H, Goellner JR, van Heerden JA (2001) Nondiagnostic thyroid fine-needle aspiration cytology: management dilemmas. Thyroid 11:1147–1151CrossRefPubMed

12.

Cravo M, Pinto R, Fidalgo P, Chaves P, Gloria L, Nobre-Leitao C, Costa Mira F (1996) Global DNA hypomethylation occurs in the early stages of intestinal type gastric carcinoma. Gut 39:434–438PubMed

13.

de Capoa A, Grappelli C, Volpino P, Bononi M, Musolino A, Ciardi A, Cavallaro A, Cangemi V (2004) Nuclear methylation levels in normal and cancerous thyroid cells. Anticancer Res 24:1495–1500PubMed

14.

Feilchenfeldt J, Totsch M, Sheu SY, Robert J, Spiliopoulos A, Frilling A, Schmid KW, Meier CA (2003) Expression of galectin-3 in normal and malignant thyroid tissue by quantitative PCR and immunohistochemistry. Mod Pathol 16:1117–1123CrossRefPubMed

15.

Feinberg AP (2004) The epigenetics of cancer etiology. Semin Cancer Biol 14:427–432CrossRefPubMed

16.

Finley DJ, Arora N, Zhu B, Gallagher L, Fahey TJ III (2004) Molecular profiling distinguishes papillary carcinoma from benign thyroid nodules. J Clin Endocrinol Metab 89:3214–3223CrossRefPubMed

17.

Finley DJ, Zhu B, Barden CB, Fahey TJ III (2004) Discrimination of benign and malignant thyroid nodules by molecular profiling. Ann Surg 240:425–436; discussion 436–427PubMed

18.

Galusca B, Dumollard JM, Chambonniere ML, Germain N, Prades JM, Peoc’h M, Estour B (2004) Peroxisome proliferator activated receptor gamma immunohistochemical expression in human papillary thyroid carcinoma tissues. Possible relationship to lymph node metastasis. Anticancer Res 24:1993–1997PubMed

19.

Gasbarri A, Marchetti C, Iervasi G, Bottoni A, Nicolini A, Bartolazzi A, Carpi A (2004) From the bench to the bedside. Galectin-3 immunodetection for improving the preoperative diagnosis of the follicular thyroid nodules. Biomed Pharmacother 58:356–359CrossRefPubMed

20.

Gasbarri A, Martegani MP, Del Prete F, Lucante T, Natali PG, Bartolazzi A (1999) Galectin-3 and CD44v6 isoforms in the preoperative evaluation of thyroid nodules. J Clin Oncol 17:3494–3502PubMed

21.

Gharib H (2004) Changing trends in thyroid practice: understanding nodular thyroid disease. Endocr Pract 10:31–39PubMed

22.

Gharib H, Goellner JR (1993) Fine-needle aspiration biopsy of the thyroid: an appraisal. Ann Intern Med 118:282–289PubMed

23.

Hernandez-Blazquez FJ, Habib M, Dumollard JM, Barthelemy C, Benchaib M, de Capoa A, Niveleau A (2000) Evaluation of global DNA hypomethylation in human colon cancer tissues by immunohistochemistry and image analysis. Gut 47:689–693CrossRefPubMed

24.

Huang Y, de la Chapelle A, Pellegata NS (2003) Hypermethylation, but not LOH, is associated with the low expression of MT1G and CRABP1 in papillary thyroid carcinoma. Int J Cancer 104:735–744CrossRefPubMed

25.

Ito Y, Tomoda C, Uruno T, Takamura Y, Miya A, Kobayashi K, Matsuzuka F, Kuma K, Miyauchi A (2004) Papillary microcarcinoma of the thyroid: how should it be treated? World J Surg 28:1115-1121CrossRefPubMed

26.

Ito Y, Uruno T, Nakano K, Takamura Y, Miya A, Kobayashi K, Yokozawa T, Matsuzuka F, Kuma S, Kuma K, Miyauchi A (2003) An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid 13:381–387CrossRefPubMed

27.

Jakubiak-Wielganowicz M, Kubiak R, Sygut J, Pomorski L, Kordek R (2003) Usefulness of galectin-3 immunohistochemistry in differential diagnosis between thyroid follicular carcinoma and follicular adenoma. Pol J Pathol 54:111–115PubMed

28.

Kini SR, Miller JM, Hamburger JI, Smith-Purslow MJ (1985) Cytopathology of follicular lesions of the thyroid gland. Diagn Cytopathol 1:123–132PubMed

29.

LiVolsi VA (1990) Thyroid tumors. In: LiVolsi VA (ed) Surgical pathology of the thyroid. Saunders, Philadelphia, pp 131–212

30.

Martins L, Matsuo SE, Ebina KN, Kulcsar MA, Friguglietti CU, Kimura ET (2002) Galectin-3 messenger ribonucleic acid and protein are expressed in benign thyroid tumors. J Clin Endocrinol Metab 87:4806–4810CrossRefPubMed

31.

Matsuo K, Tang SH, Zeki K, Gutman RA, Fagin JA (1993) Aberrant deoxyribonucleic acid methylation in human thyroid tumors. J Clin Endocrinol Metab 77:991–995CrossRefPubMed

32.

Mehrotra P, Okpokam A, Bouhaidar R, Johnson SJ, Wilson JA, Davies BR, Lennard TW (2004) Galectin-3 does not reliably distinguish benign from malignant thyroid neoplasms. Histopathology 45:493–500CrossRefPubMed

33.

Pichon B, Christophe-Hobertus C, Vassart G, Christophe D (1994) Unmethylated thyroglobulin promoter may be repressed by methylation of flanking DNA sequences. Biochem J 298 Pt 3:537–541PubMed

34.

Pineda P, Rojas P, Liberman C, Moyano L, Goecke I (2003) [Detection of malignancy markers in thyroid nodules by reverse transcriptase polymerase chain reaction (RT-PCR)]. Rev Med Chil 131:965–972PubMed

35.

Piyathilake CJ, Frost AR, Bell WC, Oelschlager D, Weiss H, Johanning GL, Niveleau A, Heimburger DC, Grizzle WE (2001) Altered global methylation of DNA: an epigenetic difference in susceptibility for lung cancer is associated with its progression. Hum Pathol 32:856–862CrossRefPubMed

36.

Piyathilake CJ, Johanning GL, Frost AR, Whiteside MA, Manne U, Grizzle WE, Heimburger DC, Niveleau A (2000) Immunohistochemical evaluation of global DNA methylation: comparison with in vitro radiolabeled methyl incorporation assay. Biotech Histochem 75:251–258PubMed

37.

Saggiorato E, Aversa S, Deandreis D, Arecco F, Mussa A, Puligheddu B, Cappia S, Conticello S, Papotti M, Orlandi F (2004) Galectin-3: presurgical marker of thyroid follicular epithelial cell-derived carcinomas. J Endocrinol Invest 27:311–317PubMed

38.

Saggiorato E, Cappia S, De Giuli P, Mussa A, Pancani G, Caraci P, Angeli A, Orlandi F (2001) Galectin-3 as a presurgical immunocytodiagnostic marker of minimally invasive follicular thyroid carcinoma. J Clin Endocrinol Metab 86:5152–5158CrossRefPubMed

39.

Soares J, Pinto AE, Cunha CV, Andre S, Barao I, Sousa JM, Cravo M (1999) Global DNA hypomethylation in breast carcinoma: correlation with prognostic factors and tumor progression. Cancer 85:112–118CrossRefPubMed

40.

Takano T, Miyauchi A, Matsuzuka F, Yoshida H, Kuma K, Amino N (2003) Ubiquitous expression of galectin-3 mRNA in benign and malignant thyroid tumors. Cancer Lett 199:69–73CrossRefPubMed

41.

Teng XD, Wang LJ, Yao HT, Li J, Ding W, Yan LP (2004) Expression of cytokeratin19, galectin-3 and HBME-1 in thyroid lesions and their differential diagnoses. Zhonghua Bing Li Xue Za Zhi 33:212–216PubMed

42.

Venkataraman GM, Yatin M, Marcinek R, Ain KB (1999) Restoration of iodide uptake in dedifferentiated thyroid carcinoma: relationship to human Na+/I-symporter gene methylation status. J Clin Endocrinol Metab 84:2449–2457CrossRefPubMed

43.

Volante M, Bozzalla-Cassione F, DePompa R, Saggiorato E, Bartolazzi A, Orlandi F, Papotti M (2004) Galectin-3 and HBME-1 expression in oncocytic cell tumors of the thyroid. Virchows Arch 445:183–188CrossRefPubMed

44.

Volante M, Bozzalla-Cassione F, Orlandi F, Papotti M (2004) Diagnostic role of galectin-3 in follicular thyroid tumors. Virchows Arch 444:309–312CrossRefPubMed

45.

Wang TS, Dubner S, Sznyter LA, Heller KS (2004) Incidence of metastatic well-differentiated thyroid cancer in cervical lymph nodes. Arch Otolaryngol Head Neck Surg 130:110–113CrossRefPubMed

46.

Weber KB, Shroyer KR, Heinz DE, Nawaz S, Said MS, Haugen BR (2004) The use of a combination of galectin-3 and thyroid peroxidase for the diagnosis and prognosis of thyroid cancer. Am J Clin Pathol 122:524–531CrossRefPubMed

47.

Xing M, Tokumaru Y, Wu G, Westra WB, Ladenson PW, Sidransky D (2003) Hypermethylation of the Pendred syndrome gene SLC26A4 is an early event in thyroid tumorigenesis. Cancer Res 63:2312–2315PubMed

48.

Xing M, Usadel H, Cohen Y, Tokumaru Y, Guo Z, Westra WB, Tong BC, Tallini G, Udelsman R, Califano JA, Ladenson PW, Sidransky D (2003) Methylation of the thyroid-stimulating hormone receptor gene in epithelial thyroid tumors: a marker of malignancy and a cause of gene silencing. Cancer Res 63:2316–2321PubMed

Title: Global DNA methylation evaluation: potential complementary marker in differential diagnosis of thyroid neoplasia
Authors: Bogdan Galusca
Jean Marc Dumollard
Sandrine Lassandre
Alain Niveleau
Jean Michel Prades
Bruno Estour
Michel Peoc’h
Publication date: 01-07-2005
Publisher: Springer-Verlag
Published in: Virchows Archiv / Issue 1/2005
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-005-1268-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Global DNA methylation evaluation: potential complementary marker in differential diagnosis of thyroid neoplasia

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2005

Atypical presentations of solitary fibrous tumors of the central nervous system: an analysis of unusual clinicopathological and outcome patterns in three new cases with a review of the literature

Hemosiderotic fibrohistiocytic lipomatous lesion: clinical correlation with venous stasis

Portal capillary C4d deposits and increased infiltration by macrophages indicate humorally mediated mechanisms in acute cellular liver allograft rejection

Primary signet-ring stromal tumor of the testis

Bizarre parosteal osteochondromatous proliferation with a t(1;17) translocation

Significance of inducible nitric oxide synthase expression in benign and malignant breast epithelium: an immunohistochemical study of 151 cases