Impact of topoisomerase IIα overexpression in the primary colon tumor on the prognosis of metastatic colorectal cancer

Abstract

Background. The evaluation of clinical and morphological characteristics is not sufficient to predict the prognosis of metastatic colorectal cancer (mRCC). Tumor aggressiveness may vary significantly even in patients with similar clinical and morphological disease characteristics. These differences are believed to be associated with molecular tumor characteristics and can be used as additional prognostic factors for patient survival.Objective: to evaluate the effect of topoisomerase IIα overexpression (topoIIα) in primary colon tumor on the mRCC prognosis.Materials and methods. The study cohort included patients with mRCC that have not previously received treatment for disseminated disease. All participants had a morphologically verified diagnosis of colon adenocarcinoma and received first-line chemotherapy with oxaliplatin and capecitabine. We evaluated both short-term and long-term treatment outcomes. We also assessed the expression of topoIIα in primary colon tumors (biopsy/surgical specimens obtained prior to initiation of first-line treatment) using immunohistochemical methods. We aimed to evaluate the association between the level of topoIIα expression and short-term/long-term treatment outcomes. We analyzed the impact of topoIIα expression in the primary tumor on the efficacy of first-line chemotherapy, progression-free survival (PFS) and overall survival (OS) in patients with mRCC.Results. Immunohistochemical evaluation of topoIIα expression in the primary tumor was conducted for 39 patients with mRCC. We found no correlation between topoIIα expression and PFS, i.e. median PFS did not differ significantly between patients with topoIIα-positive and topoIIα-negative tumors (p >0.05). Individuals with low levels of topoIIα expression in the primary tumor and those with topoIIα-negative cancer demonstrated significantly higher OS than patients with topoIIα overexpression (median OS 16.30 ± 2.0 months; 95 % confidence interval 12.32–20.28 vs 7.7 ± 4.98 months; 95 % confidence interval 0.00–17.46; p = 0.007).Conclusion. Overexpression of topoIIα is a factor of poor prognosis associated with poorer OS in patients with mRCC that received first-line chemotherapy with oxaliplatin and capecitabine.

Keywords

• topoisomerase iiα
• metastatic colorectal cancer
• first-line treatment
• chemotherapy
• oxaliplatin
• capecitabine
• molecular biomarkers