title: 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.
authors.affiliation: The James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Sumit
authors.initials: S
authors.lastname: Isharwal
authors.forename: Michael Craig
authors.initials: MC
authors.lastname: Miller
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Epstein
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Mangold
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Humphreys
authors.forename: Alan W
authors.initials: AW
authors.lastname: Partin
authors.forename: Robert W
authors.initials: RW
authors.lastname: Veltri