High Expression of Claudin-1 Protein in Papillary Thyroid Tumor and its Regional Lymph Node Metastasis Júlia Németh & Zsuzsanna Németh & Péter Tátrai & Ilona Péter & Áron Somorácz & Attila Marcell Szász & András Kiss & Zsuzsa Schaff Received: 15 April 2009 / Accepted: 25 June 2009 / Published online: 5 July 2009 # Arányi Lajos Foundation 2009 Abstract Claudins, known as major contributors in the formation of the tight junction, are differentially expressed in malignant tumors as compared to the corresponding healthy tissues. Therefore, they are thought to play a role in carcinogenesis and tumor progression. Altered expression of claudin-1 has been reported in several tumor types including endometrial, papillary renal cell and colonic carcinoma, and increased claudin-1 mRNA levels have been observed in papillary thyroid carcinoma (PTC). In this study, we aimed at determining the pattern of claudin-1 expression in various types of thyroid lesions at the protein level and investigating the immunolocalization of β-catenin reported to regulate claudin-1 expression. Samples included 19 PTCs, ten cases of corresponding regional lymph node metastasis, eight papillary microcarcinomas (PMC), 17 follicular thyroid carcinomas (FTC) and 19 follicular adenomas (FA). All cases were evaluated by quantitative immunohistochemistry. Conspicuous claudin-1 immuno- staining was detected in the majority of PTC/PMC primary tumors and lymph node metastases (19/27 and 9/10, respectively). On the other hand, we found weak or no claudin-1 expression in any of the FA and FTC cases or peritumoral non-malignant thyroid tissues. Our data prove that high claudin-1 protein expression is specific for PTC and its regional lymph node metastases, while we failed to verify that claudin-1 is regulated by β-catenin in thyroid tumors. Based on these results, claudin-1 may be a useful tumor marker for PTC. Keywords Claudin-1 . Lymph node metastasis . Papillary thyroid carcinoma . Tumor marker Abbreviations PTC Papillary thyroid carcinoma PMC Papillary microcarcinoma FTC Follicular thyroid carcinoma FA Follicular adenoma HT Hashimoto’ s thyroiditis TJ Tight junction Introduction Thyroid cancers, although they represent only 1% of all malignant diseases, are among the most common endocrine malignancies [1–3]. Most thyroid tumors derived from the follicular epithelium [2, 3]. Follicular cell-derived carcino- mas are divided into well-differentiated, poorly differenti- ated, and undifferentiated types on the basis of histological and clinical features. Well-differentiated thyroid cancers include the papillary thyroid carcinomas and follicular thyroid carcinoma [3]. Papillary carcinoma is the most common type of thyroid cancer, comprising approximately 80% of thyroid epithelial malignancies [1–4]. The more aggressive follicular carci- noma is far less prevalent (10–15% of thyroid malignan- cies) [2, 4, 5]. Neoplastic transformation is a multistep J. Németh : Z. Németh : P. Tátrai : Á. Somorácz : A. M. Szász : A. Kiss : Z. Schaff (*) 2nd Department of Pathology, Semmelweis University, Üllői út 93, 1091 Budapest, Hungary e-mail: schaff@korb2.sote.hu I. Péter National Institute of Oncology, Ráth György u. 7-9, 1122 Budapest, Hungary Pathol. Oncol. Res. (2010) 16:19–27 DOI 10.1007/s12253-009-9182-9