Topoisomerase IIα expression in mantle cell lymphoma:: a marker of cell proliferation and a prognostic factor for clinical outcome

Mantle cell lymphoma (MCL) is a malignant lymphoma associated with a relatively aggressive clinical course and a median overall survival time of 3 - 4 years. Treatment usually consists of combination chemotherapy, often including topoisomerase ( topo) inhibitors such as doxorubicin, etoposide and mitoxantrone. Topo IIalpha is an enzyme that is needed whenever uncoiling of DNA is necessary during the cell cycle. The enzyme is a marker of cell proliferation. We analyzed the expression of topo IIa in relation to Ki-67 and the clinical outcome in patients with MCL. Biopsy specimens from 95 untreated patients enrolled in two multicenter trials ( 1975 - 1985) were investigated immunohistochemically with monoclonal antibodies against topo IIalpha (Ki-S4) and Ki-67 (Ki-S5). Patients with low ( 0 - 10%) topo IIalpha expression had a median overall survival time of 49.0 months, compared to 17.0 months for patients with high ( more than 10%) topo IIa expression. The Kaplan - Meier analysis showed a significant difference in the overall survival time related to the percentage of topo IIalpha ( P<0.001) and Ki- 67 (P<0.001) positive tumor cells. Multivariate Cox regression analysis revealed the expression of topo IIalpha as the most important prognostic factor ( P<0.001) in MCL superior to the international prognostic index (IPI), the Ki- 67 index and other clinical characteristics.