Prognostic value of Her-2/neu and DNA index for progression, metastasis and prostate cancer-specific death in men with long-term follow-up after radical prostatectomy

Abstract

Abnormal DNA content in tumor cells represents large scale chromosomal alterations and reflects later changes of genetic instability. Her-2/neu oncogene is amplified in 20-30% of breast and ovarian cancer patients and is associated with poor prognosis. Therefore, we evaluated prognostic value of Her-2/neu expression and DNA content measurements in 252 clinically localized PCa patients with long-term follow-up after radical prostatectomy for progression, metastasis and PCa-specific death. Her-2/neu expression was determined by immunohistochemistry and DNA content measurements employed Feulgen-stained cancer nuclei captured using static image cytometry system. Cox proportional hazard regression and Kaplan-Meir plots were used to identify significant prognostic factors for progression, metastasis and PCa-specific death. The proportions of Her-2/neu positive and high %DNA index tumors significantly increased from nonprogressor to progressors without metastasis to progressors with metastasis (p < 0.0001; <0.0001). Further, the proportions of Her-2/neu positive and high %DNA index tumors significantly increased from patients who died from another cause without progression to those who died from another cause with progression to those died with PCa-specific death (p = 0.027; <0.0001). Her-2/neu expression and %DNA index were significant prognosticators for progression (p ≤ 0.001), metastasis (p ≤ 0.01) PCa-specific death (p ≤ 0.04) in univariate analyses. Multivariately, Her-2/neu expression and %DNA index were also significant for progression (p = 0.001), metastasis (p = 0.001) and PCa-specific death (p = 0.02). When all other clinicopathologic information is available, the increment in concordance index by addition of either Her-2/neu or DNA index was ∼2% and of both biomarkers was ∼3% for progression, metastasis and PCa-specific death free survival models. Therefore, patients with Her-2/neu positive and high %DNA index are at a higher risk for disease progression, metastasis and PCa-specific death. Further, Her-2/neu expression and %DNA index may be used with clinicopathologic parameters for prediction of longterm prognosis in PCa. © 2008 Wiley-Liss, Inc.