Prognostic role of Ki-67 expression in determination of risk of non-muscle invasive bladder cancer recurrence

Abstract

Introduction . To increase accuracy of disease prognosis in patients with bladder cancer we propose determination of expression level of several tumor markers. Objective is evaluation of prognostic significance of Ki-67 expression level in risk of non-muscle invasive bladder cancer recurrence. Materials and methods . To perform immunohistochemistry analysis of Ki-67 we used surgery material of 83 patients who underwent primary transurethral bladder resection due to non-muscle invasive cancer. We performed an analysis of correlation between Ki-67 expression level in malignant tissue removed by transurethral resection and characteristics of tumor development. We evaluated the role of Ki-67 in stratification of recurrence risk by comparing the level of Ki-67 antigen expression in patients with recurrent non-muscle invasive bladder cancer and in relapse-free patients. We present evaluation of sensitivity, specificity, and prognostic value of quantitative determination of Ki-67 expression level in relation to non-muscle invasive bladder cancer recurrence. Results . During the follow-up period, 41 cases of non-muscle invasive bladder tumor recurrence were observed. Quantitative value of the Ki-67 marker correlated with tumor differentiation grade G, malignancy grade, invasion into submucosal and muscle layers, presence of primary process, and tumor recurrence. In comparison with relapse-free patients, a significantly higher level of Ki-67 expression was observed in patients with cancer recurrence (р = 0.0035). We have determined a threshold quantitative value of Ki-67 (48 %) indicating disease recurrence. Presence of a threshold value of the Ki-67 marker showed moderate sensitivity level (less than 71 %) with relatively low specificity level (57 %). However prognostic level wasn’t high (between 63 and 65 %). Conclusion . In patients with recurrent non-muscle invasive bladder cancer an elevated level of Ki-67 expression was observed in comparison with relapse-free patients (test sensitivity was 70.7 %). Obviously, determination of molecular biomarkers, Ki-67 in particular, can potentially help distinguish highly malignant tumors with high progression and recurrence risk, which can significantly improve treatment results for these patients. However, this problem requires further research.