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

Abstract

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.

Benzoquinazoline derivatives as new agents affecting DNA processing

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