Kallikrein-related peptidase 6 regulates epithelial-to-mesenchymal transition and serves as prognostic biomarker for head and neck squamous cell carcinoma patients.

BACKGROUND: Dysregulated expression of Kallikrein-related peptidase 6 (KLK6) is a common feature for many human malignancies and numerous studies evaluated KLK6 as a promising biomarker for early diagnosis or unfavorable prognosis. However, the expression of KLK6 in carcinomas derived from mucosal epithelia, including head and neck squamous cell carcinoma (HNSCC), and its mode of action has not been addressed so far. METHODS: Stable clones of human mucosal tumor cell lines were generated with shRNA-mediated silencing or ectopic overexpression to characterize the impact of KLK6 on tumor relevant processes in vitro. Tissue microarrays with primary HNSCC samples from a retrospective patient cohort (n = 162) were stained by immunohistochemistry and the correlation between KLK6 staining and survival was addressed by univariate Kaplan-Meier and multivariate Cox proportional hazard model analysis. RESULTS: KLK6 expression was detected in head and neck tumor cell lines (FaDu, Cal27 and SCC25), but not in HeLa cervix carcinoma cells. Silencing in FaDu cells and ectopic expression in HeLa cells unraveled an inhibitory function of KLK6 on tumor cell proliferation and mobility. FaDu clones with silenced KLK6 expression displayed molecular features resembling epithelial-to-mesenchymal transition, nuclear ß-catenin accumulation and higher resistance against irradiation. Low KLK6 protein expression in primary tumors from oropharyngeal and laryngeal SCC patients was significantly correlated with poor progression-free (p = 0.001) and overall survival (p < 0.0005), and served as an independent risk factor for unfavorable clinical outcome. CONCLUSIONS: In summary, detection of low KLK6 expression in primary tumors represents a promising tool to stratify HNSCC patients with high risk for treatment failure. These patients might benefit from restoration of KLK6 expression or pharmacological targeting of signaling pathways implicated in EMT.

["Masquerade foreign body" of the conjunctiva]. / "Maskeradefremdkörper" in der Bindehaut.

CASE REPORT: An eight months old child presented with a "red eye" and a corneal erosion since a week. The parents reported on a "hair" which was invisible most of the time but appeared intermittently at the lid margin. The medical history was otherwise unremarkable. In general anaesthesia, a long structure could be easily extracted. The tapering structure disclosed several tiny hair-like filaments sprouting from the thickened end. This end was embedded within a fold of conjunctiva, thus giving the impression of a hair sheath. Clinically, an ectopic "giant hair" was supposed. Histology, however, revealed plants cells and a birefringence too high for a hair so that a diagnosis of a plant foreign body was established. CONCLUSION: Conjunctival foreign bodies may be overlooked especially in young children with no history of foreign body acquisition. They may occur as a "masquerade foreign body".