Prognostic value analysis of urokinase-type plasminogen activator receptor in oral squamous cell carcinoma: an immunohistochemical study

Abstract

Background: Oral squamous cell carcinoma (OSCC) represents the most common oral malignancy. Despite recent advances in therapy, up to 50% of the cases have relapse and/or metastasis. There is therefore a strong need for the identification of new biological markers able to predict the clinical behaviour of these lesions in order to improve quality of life and overall survival. Among tumour progression biomarkers, already known for their involvement in other neoplasia, a crucial role is ascribed to the urokinase-type plasminogen activator receptor (uPAR), which plays a multiple role in extracellular proteolysis, cell migration and tissue remodelling not only as a receptor for the zymogen pro-uPA but also as a component for cell adhesion and as a chemoattractant. The purpose of this study was to gain information on the expression of uPAR in OSCC and to verify whether this molecule can have a role as a prognostic/predictive marker for this neoplasia.

Methods: In a retrospective study, a cohort of 189 OSCC patients was investigated for uPAR expression and its cellular localization by immunohistochemistry. As standard controls, 8 normal oral mucosal tissues free of malignancy, obtained from patients with no evidence or history of oral cavity tumours, were similarly investigated. After grouping for uPAR expression, OSCCs were statistically analyzed for the variables age, gender, histological grading (G), tumour size, recurrence, TNM staging and overall survival rate.

Results: In our immunohistochemical study, 74 cases (39.1%) of OSCC showed a mostly cytoplasmic positivity for uPAR, whereas 115 were negative. uPAR expression correlated with tumour differentiation grade and prognosis: percentage of positive cases was the greatest in G3 (70.4%) and patients positives for uPAR expression had an expectation of life lower than those for uPAR negatives.

Conclusion: The results obtained in this study suggest a role of uPAR as a potential biomarker useful to identify higher risk subgroups of OSCC patients.

Figure 1

uPAR expression in OSCC. A: Strong cytoplasmic positivity of neoplastic epithelial cells in poorly differentiated OSCC (G3) (× 250). B: Weak cytoplasmic positivity of epithelial cells of invasive front in moderately differentiated OSCC (G2) (× 200). C: Focal strong positivity in stromal and inflammatory peritumoral cells in moderately differentiated OSCC (G2) (× 160). D: Negativity of an adjacent section incubated with an isotype-matched monoclonal control antibody (× 400).

Figure 2

Prognostic value of uPAR expression. Kaplan-Meier curves for OSCC patients correlating uPAR expression and overall survival (A) (p = 0.0053), survival in grade 1 (B) (p = 0.0447), grade 2 (C) (p = 0.3427) and grade 3 (D) (p = 0.7143) tumours. Dotted line, uPAR negative cases ; continuous line, uPAR positive cases.