RESEARCH The Prognostic Role of Claudins in Head and Neck Squamous Cell Carcinomas Györgyi A. Nelhűbel & Boróka Károly & Balázs Szabó & Gábor Lotz & András Kiss & József Tóvári & István Kenessey Received: 12 April 2013 / Accepted: 18 June 2013 # Arányi Lajos Foundation 2013 Abstract The expression of tight junction proteins is fre- quently altered in epithelial cancers. The loss of cell-cell adhesion associates with enhanced metastatic potential, which underlies the role of altered expression pattern of tight junc- tion component claudins (CLDNs). Our study assessed the expression of CLDN 1, 2, 3, 4, 7, 8 and 10 in squamous cell carcinoma of the head and neck region (HNSCC) including oropahrynx, larynx, and hypopharynx in comparison to nor- mal epithelial tissue of the same patient. The surgical samples were examined by tissue microarray and immunohistochem- istry, the expression was calculated by H-score, which took account of intensity and percentage of positivity as well. Both normal and cancerous tissue proved negative for CLDN 3, 8 and 10. Normal epithelia showed mild expression of CLDN 4, but the minimal positivity disappeared in squamous cancer. In case of CLDN 1 and CLDN 7 we demonstrated significant- ly increased intensity in cancer, while CLDN 2 showed de- creased expression compared with normal epithelium. The normal polarity and distribution of claudins were lost in HNSCC. Moreover, preserved expression of CLDN 2 (but not that of 1 and 7) was associated with better survival, which suggested a potential prognostic role of CLDN 2. Keywords Claudin . Head and neck squamous cell carcinoma . Prognosis . Immunohistochemistry . Tight junction Introduction Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent tumor type with approximately 650,000 new cases each year and 350,000 deaths per year worldwide [1]. In Hungary HNSCC is the third most frequent malignant tumor type among males, and even though the incidence is usually much higher in southern Europe than in Central and Northern Europe, Hungary is ranked first in the world with respect to its incidence and mortality as well [2, 3]. Despite of improved tumor detection and advanced treatment modal- ities, 5-year overall survival did not change significantly in the past few years, usually more than 50% of HNSCC patients die [4, 5]. One of the most important factors of therapeutic decisions is clinical stage: early-stage (I–II) tu- mors are treated with surgery or irradiation as monotherapy, while the treatment of advanced tumors combines surgical tools and chemo-radiotherapy [6]. Based on the molecular characteristics of HNSCC, new treatment modalities were introduced, for instance anti-EGFR therapies [5]. Since the predictive value of traditional markers such as anatomical location (oral cavity, pharynx or larynx), extension, depth of invasion, grade, exophytic or endophytic spreading proved very limited, new parameters have been adopted, e.g. apo- ptosis index, Ki67 proliferation index, and expression of p53 [7–10]. Another determining factor is the etiology of cancer on its own: most of these malignancies link to extensive tobacco and alcohol consumption, however, HPV-positive squamous cancers showed better clinical outcome [8]. None- theless, the efficacy of these prognostic factors is limited, therefore, new markers are urgently needed. Györgyi A. Nelhübel and Boróka Károly are contributed equally to this work G. A. Nelhűbel : J. Tóvári Department of Experimental Pharmacology, National Institute of Oncology, Budapest, Hungary G. A. Nelhűbel : B. Károly : B. Szabó Department of Otolaryngology and Head and Neck Surgery, Semmelweis University, Budapest, Hungary B. Károly : G. Lotz : A. Kiss : I. Kenessey (*) 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest H-1091, Hungary e-mail: steveken12@yahoo.com Pathol. Oncol. Res. DOI 10.1007/s12253-013-9665-6