title: The level of secretory leukocyte protease inhibitor is decreased in metastatic head and neck squamous cell carcinoma.
abstract: Head and neck squamous cell carcinomas (HNSCC) represent the sixth largest group among all human malignancies. However, the exact molecular mechanisms inducing the genesis and the progression of metastasis in these tumors are poorly understood. The identification of molecular alterations involved in metastasis of HNSCC might influence the value of clinical diagnostics, impact therapy strategies and finally improve the prognosis of the patients. The purpose of this study was to identify clinically relevant alterations at the transcriptional and translational levels, when comparing metastatic (N+) and non-metastatic (N0) primary HNSCC. Three transcripts HERPUD1, SLPI and RAD51 were selected for further validation based on their association with carcinogenesis and metastasis. Quantitative real-time-PCR was performed to determine the mRNA expression levels. For subsequent confirmation of the results, immunohistochemistry was performed applying a monoclonal anti-SLPI antibody on 121 HNSCC tumor specimens (N0, n=40; N+, n=81). In metastatic primary cancer, SLPI mRNA showed 5.9-fold lower expression in comparison with non-metastatic primary cancer (p=0.0092). Immunohistochemical staining revealed a fold change of -1.79 between the N+ and the N0 group (p=0.0002). The results presented here clearly indicate the repression of SLPI, measurable on both, mRNA and protein levels in metastatic primary HNSCC as compared to non-metastatic HNSCC. Therefore, it can be assumed that SLPI might have a substantial protective effect on the metastasis process of HNSCC.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts-University Kiel, Arnold-Heller-Strasse 3, Haus 27, 24105 Kiel, Germany. ccordes@hno.uni-kiel.de
authors.forename: Christian
authors.initials: C
authors.lastname: Cordes
authors.forename: Robert
authors.initials: R
authors.lastname: Häsler
authors.forename: Christian
authors.initials: C
authors.lastname: Werner
authors.forename: Tibor
authors.initials: T
authors.lastname: Görögh
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken
authors.forename: Lena
authors.initials: L
authors.lastname: Hebebrand
authors.forename: W Martin
authors.initials: WM
authors.lastname: Kast
authors.forename: Markus
authors.initials: M
authors.lastname: Hoffmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Petra
authors.initials: P
authors.lastname: Ambrosch
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000503:physiopathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000235:genetics; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D053481:Secretory Leukocyte Peptidase Inhibitor