title: Immunohistochemical analysis and prognostic value of cathepsin D determination in laryngeal squamous cell carcinoma.
abstract: Cathepsin D, a protease with the capability of degrading matrix proteins, is implicated in the process of breast and colorectal cancer invasion and metastasis. Biochemical studies in laryngeal cancer have shown a potential prognostic significance of cathepsin D content determination. We studied immunohistochemical positivity of cathepsin D in tumor epithelium and stroma of 61 surgical specimens of squamous cell laryngeal cancer. Immunohistochemical reaction was quantitatively assessed using a PC-based image analysis system SFORM-VAMS. The results were correlated to clinical and morphological parameters and survival. Immunohistochemical positivity was noted in neoplastic cells and tumor stroma. Significant prognostic value for cathepsin D was established separately for epithelial tumor component and tumor stroma using log-rank test, the Cox proportional hazards regression model, and C4.5 machine learning system. In all groups, patients above the median cathepsin D staining showed significantly shorter survival time. C4.5 machine learning system extracted cutoff values for the decision tree that defines the probabilities of patients survival and death with high sensitivity (92.8% alive, 73.6% dead), 100% specificity, and 86.9% accuracy. This makes immunohistochemical cathepsin D estimation an independent prognostic parameter in laryngeal carcinomas within a 5-year period from the time of tumor surgery.
authors.affiliation: Institute of Pathology, Department of Pharmacology, and ENT Clinic, Medical Faculty University of Zagreb, Croatia.
authors.forename: S
authors.initials: S
authors.lastname: Seiwerth
authors.forename: N
authors.initials: N
authors.lastname: Stambuk
authors.forename: P
authors.initials: P
authors.lastname: Konjevoda
authors.forename: N
authors.initials: N
authors.lastname: Masić
authors.forename: A
authors.initials: A
authors.lastname: Vasilj
authors.forename: M
authors.initials: M
authors.lastname: Bura
authors.forename: I
authors.initials: I
authors.lastname: Klapan
authors.forename: S
authors.initials: S
authors.lastname: Manojlović
authors.forename: D
authors.initials: D
authors.lastname: Danić
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D002402:Cathepsin D / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000201:enzymology* / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis
chemical_list: D002402:Cathepsin D