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 <or= 0.001), metastasis (p <or= 0.01) PCa-specific death (p <or= 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 approximately 2% and of both biomarkers was approximately 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 long-term prognosis in PCa.