Expression of stefin A is of prognostic significance in squamous cell carcinoma of the head and neck

Lysosomal proteases cathepsins B and L (CB, CL) and their endogenous inhibitors stefins A and B (SA, SB) are associated with tumor cell invasion and metastasis. The purpose of this study was to determine the immunohistochemical (IHC) localization of these parameters in tissue sections of 65 patients with operable head and neck squamous cell carcinoma (HNSCC) and to evaluate the prognostic significance of the observed IHC reactions. In SCC cells, a dot-like staining pattern for CB and CL was especially polarized in the perinuclear area and for stefins the characteristic IHC pattern was a diffuse cytoplasmic reaction. Higher SA immunoreactivity scores were found prognostically advantageous in univariate survival analysis [locoregional control (LRC), P = 0.003; disease-free survival (DFS), P = 0.023; disease-specific survival (DSS), P = 0.030] and appeared significant for predicting LRC (P = 0.019) in a multivariate setting. Among node-positive extracapsular extension-negative patients, SA positivity correlated with a favorable outcome (LRC, P = 0.094; DFS, P = 0.013; DSS, P = 0.012). In conclusion, SA immunoreactivity in tumor cells was related to a favorable prognosis. In the neck node-positive extracapsular extension-negative subgroup, SA immunoreactivity scores can be used to identify patients at increased risk for disease relapse.