Different topoisomerase IIa protein expression patterns affect prognosis in tongue squamous cell carcinoma: a quantitative digital image analysis study

Aim:  Topoisomerases represent a class of nucleic enzymes involved in the DNA replication, transcription and also chromosome topological formation. Topoisomerase IIa (Topo Iia – gene location 17q21) inhibition promotes cell death and for this reason, it is a target for specific chemotherapy (anthracyclines, podophyllotoxines). Our aim was to investigate the potential prognostic significance of its protein expression in squamous cell carcinomas of the tongue (TSCCs) based on a quantitative, digital image analysis method. Materials and methods:  We analysed immunohistochemically eighty-seven (n = 87) archival, primary TSCCs using a monoclonal anti-Topo IIa antibody. A computerised image analysis assay was applied for the evaluation of the results [nuclear labelling index (NLI)]. Survival analysis was also performed. Results:  Topo IIa protein was overexpressed in 48/87 (55.1%) cases. High NLI values were detected in 17/48 (35.4%), whereas moderate levels of expression were detected in 31/48 (64.6%) cases. Statistical significance was not assessed correlating overall protein expression to grade or stage of the examined tumours (P = 0.88, P = 0.73, respectively), but only to the anatomical region (P = 0.04). Cox regression analysis showed that Topo IIa and also the size of the tumours were strongly associated to the survival of the patients (P = 0.01, P = 0.02, respectively). Conclusions:  Topo IIa protein overexpression is a frequent event in TSCCs. Topo IIa may be used as a prognostic factor and also as a basis for targeted chemotherapy strategies in TSCCs. Furthermore, digital image analysis improves the quantification of immunohistochemical stains in an accurate and fast way.