Clinical Significance of Claudin Expression in Oral Squamous Cell Carcinoma

A change in claudin expression has been demonstrated in various tumors. The present study specifically compares claudin expression in oral squamous cell carcinoma (OSCC) with healthy oral epithelium from the same individual and analyzes the association between claudin expression and the clinically relevant course parameters. Our study includes tissue samples and clinically relevant follow-up data from 60 patients with primary and untreated OSCC. The oral mucosa was analyzed via Western blot for the expression of claudin-1, -2, -3, -4, -5, and -7. Importantly, the tumor and healthy tissues were obtained pairwise from patients, allowing for intraindividual comparisons. Both the healthy and tumor epithelium from the oral cavity did not express the claudin-3 protein. The intraindividual comparison revealed that, in OSCC, claudin-2 expression was higher, and the expression of claudin-4, -5, and -7 was lower than in healthy epithelium. An association was found between increased claudin-2 expression and shorter relapse-free survival. In addition, the reduced expression of claudin-4 had a negative impact on relapse-free survival. Furthermore, associations between the reduced expression of claudin-7 and the stage of a tumor, or the presence of lymph node metastases, were found. Thus, the expression level of claudin-2, -4, and -7 appears to be predictive of the diagnosis and prognosis of OSCC

Investigation of claudin expression in the Squamous cell carcinoma of the oral mucosa

Zielsetzung: Eine Veränderung der Claudin-Expression wurde in verschiedenen Tumoren nachgewiesen. In der vorliegenden Studie wird speziell die Claudin-Expression im Plattenepithelkarzinom der Mundschleimhaut mit gesundem oralem Epithel des gleichen Individuums verglichen. Außerdem wird eine mögliche Korrelation zwischen Claudin-Expression und klinisch relevanten Verlaufsparametern abgeklärt. Material und Methoden: Die vorliegende Studie umfasst Gewebeproben und klinisch relevante Verlaufsdaten von 60 Patienten mit primärem und unbehandeltem Plattenepithelkarzinom der Mundhöhle. Tumorgewebe und Gewebe der gesunden Mundschleimhaut der Wange des gleichen Patienten wurden im Western Blot auf die Expression von Claudinen-1, -2, -3, -4, -5 und -7 untersucht. Das Vorhandensein von Claudin-3 im gesunden und Tumorepithel wurde zusätzlich mit einem Pulldown Assay und Massenspektroskopie überprüft. Bei ausgewählten Patienten wurde zusätzlich die Lokalisation dieser Claudine mittels Konfokalmikroskopie validiert. Ergebnisse: Das gesunde und das Tumorepithel der Mundhöhle exprimiert kein Claudin-3 Protein. Im intraindividuellen Vergleich wird signifikant mehr Claudin-2 und weniger Claudin-4, -5 und -7 im oralen Plattenepithelkarzinom exprimiert. In gesundem, oralem Plattenepithel wurden diese Claudine hauptsächlich in der Zellmembran nachgewiesen, wohingegen eine Dislokation von Claudin-1, -4 und -7 in das Zytoplasma und von Claudin-4 und -5 in den Zellkern bei oralen Plattenepithelkarzinomen beobachtet wurde. Ein relevanter Zusammenhang zwischen verstärkter Claudin-2-Expression oder verminderter Expression von Claudin-4 und einem kürzeren rezidivfreien Überleben wird gezeigt. Außerdem besteht eine Korrelation zwischen reduzierter Expression von Claudin-7 und einem fortgeschrittenen Tumorstadium sowie der Anwesenheit von Lymphknotenmetastasen. Schlussfolgerung: Hiermit scheint die Expression der Claudine-2, -4 und -7 für die Diagnose und Prognose des oralen Plattenepithelkarzinoms relevant zu sein.Aims: A change in claudin expression has been demonstrated in various tumors. The present study specifically compares claudin expression in squamous cell carcinoma of the oral mucosa with healthy oral epithelium from the same individual. In addition, the possible correlation between claudin expression and clinically relevant progression parameters is clarified. Material and Methods: The present study includes tissue samples and clinically relevant follow-up data from 60 patients with primary and untreated squamous cell carcinoma of the oral cavity. Tumor tissue and tissue of the healthy oral mucosa of the cheek of the same patient were examined in Western blot analysis for the expression of claudin-1, -2, -3, -4, -5 and -7. The presence of claudin-3 in the healthy and tumor epithelium is additionally checked using a pulldown assay and mass spectrometry. In selected patients, the localization of these claudins was also validated using confocal microscopy. Results: Both, healthy and tumor epithelium of the oral cavity do not express claudin-3 protein. In an intraindividual comparison, significantly more claudin-2 and less claudin-4, -5 and -7 are expressed in oral squamous cell carcinoma. In healthy oral squamous epithelium these claudins were mainly found in the cell membrane, whereas dislocalization of claudin-1, -4 and -7 in the cytoplasm and of claudin-4 and -5 in the cell nucleus was observed in oral squamous cell carcinoma. A relevant connection between overexpression of claudin-2 or reduced expression of claudin-4 and a shorter relapse-free survival is shown. There is also a correlation between reduced expression of claudin-7 and an advanced tumor stage and the presence of lymph node metastases. Conclusion: The expression of claudin-2, -4 and -7 seems to be relevant for the diagnosis and prognosis of oral squamous cell carcinoma