Objectives: S100A4 is a calcium-binding protein related to the metastatic potential of carcinoma. In order to elucidate its contribution to the progression of thyroid carcinoma, we investigated S100A4 expression in various thyroid neoplasms. Methods: We immunohistochemically examined S100A4 expression in 195 cases of thyroid neoplasms. Results: Although S100A4 was absent in normal follicular cells and follicular adenoma, S100A4 was positive in all 115 cases of papillary carcinoma examined, including 58 microcarcinomas. However, a significant relationship could not be established between S100A4 expression and clinicopathological features of papillary carcinoma. In follicular carcinoma, the widely invasive type expressed S100A4 more frequently than the minimally invasive type (p = 0.0028). In anaplastic carcinoma, S100A4 was expressed in 61.9% of cases, but the incidence was significantly lower (p < 0.0001) than that in papillary carcinoma. Conclusions: These findings suggest that (1) S100A4 plays a constitutive role in papillary carcinoma and (2) S100A4 may be a useful marker for early the detection of this carcinoma.

Keywords:
S100A4, Thyroid carcinoma, Immunohistochemistry
1.
Li Volsi VA, Asa SL: The demise of follicular carcinoma of the thyroid gland. Thyroid 1994;4:233–237.
2.
Fagin JA: Molecular genetics of tumors of thyroid follicular cells. Thyroid, ed 8, Lippincott Williams & Wilkins 2001, pp 886–898.
3.
Ito Y, Uruno R, Nakano K, Takamura Y, Miya A, Kobayashi K, Yokozawa T, Matsuzuuka F, Kuma S, Kuma K, Miyauchi A: An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid 2003;13:381–388.
4.
Aldinger KA, Samaan NA, Ibanez M, Hill CS, Jr: Anaplastic carcinoma of the thyroid: A review of 84 cases of spindle and giant-cell carcinoma of the thyroid. Cancer 1978;41:2267–2275.
5.
Watanabe Y, Kobayashi R, Ishikawa T, Hidaka H: Isolation and characterization of a calcium-binding protein derived from mRNA termed p9Ka, pEL-98, 18A2, or 42A by the newly synthesized vasorelaxant W-66 affinity chromatography. Arch Biochem Biophys 1992;292:563–569.
6.
Ebralidze A, Tulchinsky E, Grigorian M, Afanasyeva A, Senin V, Revazova E, Lukanidin E: Isolation and characterization of a gene specifically expressed in different metastatic cells and whose deduced gene product has a high degree of homology to a Ca2+-binding protein family. Genes Dev 1989;3:1086–1093.
7.
Davies BR, Davies MPA, Gibbs FEM, Barraclough R, Rudland PS: Induction of the metastatic phenotype by transfection of a benign rat mammary epithelial cell line with the gene for p9Ka, a rat calcium-binding protein, but not with the oncogene EJ-ras-1. Oncogene 1993;8:999–1008.
8.
Takenaga K, Nakamura Y, Endo H, Sakiyama S: Involvement of S100-related calcium-binding protein pEL98 (or mts1) in cell motility and tumor cell invasion. Jpn J Cancer Res 1994;85:831–839.
9.
Sherbet GV, Lakshmi MS: S100 A4 (MTS1) calcium binding protein in cancer growth, invasion and metastasis. Anticancer Res 1998;18:2415–2421.
10.
Ambartsumian GM, Lykkesfeldt N, Bastholm L, Elling F, Georgiev G, Lukanidin E: Effects of mts1 (100A5) expression on the progression of human breast cancer cells. Int J Cancer 1996;67:831–841.
11.
Rudland PS, Platt-Higgins A, Renshaw C, West CR, Winstanley JHR, Robertson L, Barraclough R: Prognostic significance of the metastasis-inducing protein S100A4 (p9Ka) in human breast cancer. Cancer Res 2000;60:1595–1603.
12.
Platt-higgins AM, Renshaw CA, West CR, Winstanley JHR, Rudland DS, Barraclough R, Rudland PS: Comparison of the metastasis-inducing protein S100A4 (p9Ka) with other prognostic markers in human breast cancer. Int J Cancer 2000;89:198–208.
13.
Pedersen KB, Nesland JM, Fodstad O, Maelandsomo GM: Expression of S100A4, E-cadherin, α- and β-catenin in breast cancer biopsies. Br J Cancer 2002;87:1281–1286.
14.
Takenaga K, Nakanishi H, Wada K, Suzuki M, Matsuzaki O, Matsuura A, Endo H: Increased expression of S100A4, a metastasis-associated gene, in human colorectal adenocarcinomas. Clin Cancer Res 1997;3:2309–2316.
15.
Taylor S, Herrington S, Prime W, Rudland PS, Barraclough R: S100A4 (p9Ka) protein in colon carcinoma and liver metastases: Association with carcinoma cells and T-lymphocytes. Br J Cancer 2002;86:409–416.
16.
Gongoll S, Peters G, Mengel M, Piso P, Klempnauer J, Kreipe H, Wasielewski RV: Prognostic significance of calcium-binding protein S100A4 in colorectal cancer. Gastroenterology 2002;123:1478–1484.
17.
Komatsu K, Murata K, Kameyama M, Ayaki M, Mukai M, Ishiguro S, Miyoshi J, Tatsuta M, Inoue M, Nakamura H: Expression of S100A6 and S100A4 in matched samples of human colorectal mucosa, primary colorectal adenocarcinomas and liver metastases. Oncology 2002;63:192–200.
18.
Flatmark K, Pedersen KB, Nesland JM, Rasmussen H, Aamodt G, Mikalsen SO, Bjornland K, Fodstad O, Maelandsmo GM: Nuclear localization of the metastasis-related protein S100A4 correlates with tumour stage in colorectal cancer. J Pathol 2003;200:589–595.
19.
Gupta S, Hussain T, Maclennan GT, Fu P, Patel J, Mukhtar H: Differential expression of S100A2 and S100A4 during progression of human prostate adenocarcinoma. J Clin Oncol 2003;21:106–112.
20.
Ninomiya I, Ohta T, Fushida S, Endo Y, Hashimoto T, Yagi M, Fujimura T, Nishimura G, Tani T, Shimizu K, Yonemura Y, Heizmann CW, Schfer BW, Sasaki T, Miwa K: Increased expression of S100A4 and its prognostic significance in esophageal squamous cell carcinoma. Int J Oncol 2001;18:715–720.
21.
Nakamura T, Ajiki T, Murao S, Kamigaki T, Maeda S, Ku Y, Kuroda Y: Prognostic significance of S100A4 expression in gall bladder cancer. Int J Oncol 2002;20:937–941.
22.
Davies BR, O’Donnell M, Durkan GC, Rudland PS, Barraclough R, Neal DE, Mellon JK: Expression of S100A4 protein is associated with metastasis and reduced survival in human bladder cancer. J Pathol 2002;196:292–299.
23.
Rosty C, Ueki T, Argani P, Jansen M, Yeo CJ, Cameron JL, Hruban RH, Goggins M: Overexpression of S100A4 in pancreatic ductal adenocarcinomas is associated with poor differentiation and DNA hypomethylation. Am J Pathol 2002;160:45–50.
24.
Cho YG, Nam SW, Kim TY, Kim YS, Kim CJ, Park JY, Lee JH, Kim HS, Lee JW, Park CH, Song YH, Lee SH, Yoo NJ, Lee JY, Park WS: Overexpression of S100A4 is closely related to the aggressiveness of gastric cancer. APMIS 2003;111:539–545.
25.
Grigorian M, Andresen S, Tulchinsky E, Kriajevska M, Carlberg C, Kurse C, Cohn M, Ambartsumian N, Christensen A, Selivanova G, Lukanidin E: Tumor suppressor p53 protein is a new target for the metastasis-associated Mts1/S100A4 protein: functional consequences of their interaction. J Biol Chem 2001;276:22699–22708.
© 2004 S. Karger AG, Basel
2005
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