title: Cytokeratin and protein expression patterns in squamous cell carcinoma of the oral cavity provide evidence for two distinct pathogenetic pathways.
abstract: Squamous cell carcinoma (SCC) of the oral cavity is a morphological heterogeneous disease. Various cytokeratin (CK) expression patterns with different prognostic values have been described, but little is known concerning the underlying biological cell mechanisms. Therefore, the present study investigated 193 cases of oral SCCs using immunohistochemistry for α/β/γ-catenin, glucose transporter 1, caspase-3, X-linked inhibitor of apoptosis protein, hypoxia inducible factor-1α, carbonic anhydrase 9, heat shock protein (hsp) 70, mast/stem cell growth factor receptor, p21, p27, p16, p53, B-cell lymphoma 6, epidermal growth factor receptor, cyclin D1 and CK1, 5/6, 8/18, 10, 14 and 19. Expression patterns were analyzed with biomathematical permutation analysis. The present results revealed a significant association between the expression of low-molecular weight CK8/18 and 19 and a high-tumor grade, β and γ-catenin expression, deregulated cell cycle proteins and a predominant localization of the tumor on the floor of the mouth. By contrast, expression of high-molecular weight CK1, 5/6, 10 and 14 was significantly associated with the expression of p21 and hsp70. In conclusion, the current study presents evidence for the existence of two parallel pathogenetic pathways in oral SCCs, characterized by the expression of low- and high-molecular weight CKs. Additional studies are required to demonstrate the extent that these results may be used to improve therapeutic regimens.
authors.affiliation: Institute of Pathology, D-33098 Paderborn, Germany.
authors.forename: Gesche
authors.initials: G
authors.lastname: Frohwitter
authors.affiliation: Institute of Pathology, D-33098 Paderborn, Germany; Department of Pathology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
authors.forename: Horst
authors.initials: H
authors.lastname: Buerger
authors.affiliation: Department of Pathology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: VAN Diest
authors.affiliation: Institute of Bioinformatics, Faculty of Medicine, University of Münster, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Korsching
authors.affiliation: Department of Cranio and Maxillofacial Surgery, University Hospital Muenster, D-48149 Münster, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kleinheinz
authors.affiliation: Department of Cranio and Maxillofacial Surgery, Marienhospital Stuttgart, D-70199 Stuttgart, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fillies
keywords: cytokeratins; oral cavity; squamous cell carcinoma; tumor biology