The association between the prognosis and the localization and expressionof heparanase in human laryngeal squamous cell carcinoma

Abstract

Objective:The aim of this study is to explore the expression of heparanase(HPA) in human laryngeal squamous cell carcinoma and its correlation with the clinical pathologic features, such as clinical stage, T grade, lymph node metastasis and cellular differentiation. At the same time, to evaluate the relationship between heparanse localization and expression in human laryngeal squamous cell carcinoma (HLSCC) and tumor prognosis and patients survival. Method: The expression levels of HPA in HLSCC tissues of 73 cases and benign lesions of 38 cases(control) were detected via immunohistochemistry. The correlation of HPA expression with various clinical pathologic features was evaluated with single factor analysis.The Fisher exact test and chisquare tests were used to compare categorical data. Univariate survival was evaluated by KaplanMeier curves and tested using logrank test. Multivariate Cox proportionalhazards regression was used to evaluate independent prognostic factors associated with survival. Result: The positive expression rate of HPA in 73 HLSCC patients and benign lesions of 38 cases were 76.71%（56/73）and 21.05%（8/38）respectively（P<0.05）. The clinical pathologic analysis showed that HPA level had a relationship with the clinical stage, T grade, cellular differentiation and lymph node metastasis(P<0.05), while not with gender, age and clinical types(P>0.05). Survival analysis showed that the patients with high HPA expression had significantly poorer outcome as compared with the patients with low HPA expression. The medium survival time and the 5year survival rate were 24 months and 43.33% in highheparanase group, 56 months and 61.54% in the lowheparanase group and 65 months and 70.59% in the noneheparanse group(P=0.010). The survival was related to clinical stage, T grade, lymph node metastasis, and cellular differentiation(P<0.05), but not with age, sex and clinical types(P>0.05).In multivariate Cox proportionalhazards regression analysis, the results suggested that lymph node metastasis, hepanranase expression level and heparanase localization were independent prognosis factor for HLSCC. Moreover, hepanranase localization correlated with patient outcome. Kaplan Meier analysis demonstrated statistically significantly difference for 5-years overall survival rate between the patients with HPA nuclear staining and the patients with HPA cytoplasmic staining(P<0.05).Conclusion:HPA was related with worse overall survival and could be considered as a potential marker of poor prognosis. Cytoplasmic staining of heparanase inversely correlated with patients survival and predicts poor prognosis, whereas nuclear heparanase predicts a favourable outcome.