Topoisomerase II alpha Protein Expression Is Predictor of Outcome in Gleason Score ≥ 7 Prostate Cancer Patients Treated Surgically: An Immunohistochemical Comparison to MIB1
JC Cheville, CM Ida, RJ Karnes, A Nair, G Vasmatzis. Mayo Clinic, Rochester, MN
Background: Tumor proliferative status is often used as an indicator of biological aggressiveness. MIB1 is the prototypical immunohistochemical (IHC) proliferative marker in diagnostic histopathology. Topoisomerase II alpha (TOP2A), an enzyme involved in DNA synthetic period, is an alternative IHC proliferative marker. Recently, its gene (TOP2A) has been described as the strongest predictor of outcome in a prognostic model for high Gleason Score (GS) prostate cancer (GS ≥ 7). This model also included the TMPRSS2-ERG fusion, which results in ERG gene overexpression. We performed an IHC study to evaluate the prognostic value of TOP2A in comparison to MIB1 among GS ≥ 7 prostate cancer in the context of ERG status.
Design: GS ≥ 7 prostate cancer patients that developed systemic progression or died of prostate cancer within 5 years following surgery (n=140, cases) and patients free of disease within at least 7 years of follow-up (n=117, controls) were selected. A computerized score combining GS, margin status and preoperative serum PSA, was used to match cases and controls. ERG mRNA levels were measured by qRT-PCR and defined as high (ERG+) or low (ERG-) gene expression. IHC studies directed against TOP2A protein and Ki-67 antigen (MIB1 clone) were performed. IHC staining was quantified using IHC Score Software (Bacus Laboratories, Inc.) to obtain TOP2A and MIB1 labeling indices (LIs).
Results: LIs mean ± SD for cases and controls were 3.45±5.18 (range,0.02-30.74) and 0.92±1.34 (range,0.01-7.09) for TOP2A, and 7.99±8.86 (range,0.11-43.58) and 3.25±3.33 (range,0.04-18.05) for MIB1, respectively (pீ0.001). TOP2A was a better predictor of outcome than MIB1 (AUC 0.73 for TOP2A vs.0.70 for MIB1), especially among ERG- prostate cancer (AUC 0.77 for TOP2A vs.AUC 0.72 for MIB1).
Conclusions: TOP2A IHC protein expression was a superior predictor of systemic progression and death than traditional MIB1 proliferative marker in GS ≥ 7 prostate cancer patients treated surgically, especially in the group without ERG overexpression. Thus, TOP2A protein expression is a potential prognostic tool to individualize adjuvant therapy based on risk of systemic progression.
Category: Genitourinary (including renal tumors)
Monday, March 22, 2010 8:00 AM
Platform Session: Section A, Monday Morning