Prognostic Value Of Her-2/Neu And DNA Index For Progression, Metastasis And Prostate Cancer-Specific Death After Radical Prostatectomy

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Cancer / Oncology
Article Date: 27 Oct 2008 - 1:00 PDT

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UroToday.com - In the online version of the International Journal of Cancer, Dr. Sumit Isharwal and associates from Johns Hopkins University reported on the prognostic association between the Her-2/neu oncoprotein expression, abnormal DNA content and prostate cancer (CaP) progression. The investigators found a positive correlation.

The initial study cohort consisted of 252 men with clinically localized CaP treated with radical prostatectomy between 1980 and 1994. Patients were stratified into having Gleason score <7 or >7. For DNA content analysis, a minimum of 125 intact nuclei were captured from the cancer area for each patient. DNA content measurements were calculated and a % DNA index value generated. Her-2/neu expression in tissue sections was assessed by immunohistochemistry staining and counting. Patients were Her-2/neu negative, focally positive, and diffusely positive, if staining was present, in <5%, 5-30%, and >30%, respectively.

A total of 147 patients had disease progression, 43.8% with distant metastasis while 26.3% died due to CaP. Mean follow-up after surgery was 15.3 years. The likelihood of disease progression after 10 and 15 years was 11% and 3.5%, respectively. The proportion of Her-2/neu positive tumors significantly increased from non-progressors (53%), to progressors without metastasis (70%), to progressors with metastasis (87%). The proportions of high %DNA index tumors increased from non-progressors (41%), to progressors without metastasis (69%), to progressors with metastasis (80%). Also, the proportions of Her-2/neu positive tumors significantly increased from patients who died from another cause without progression (62%) to men who died from another cause with progression (72%) to those who died due to CaP (86%). This was also the case for %DNA index, with the proportions of high %DNA index tumors significantly increased from patients who died from another cause without progression (38%) to men who died from another cause with progression (64%) to those who died due to CaP (83%).

Clinical and pathological variables, significant in univariate analysis, were included in multivariate analysis. For metastasis-free survival, Gleason score, %DNA index and Her-2/neu expression were significant. Gleason score, %DNA index, lymph node involvement, and Her-2/neu were significant for time to CaP-specific death in multivariable analysis. A bootstrap resampling procedure in 200 replications supported these findings. These data suggest that Her-2/neu expression and %DNA are clinicopathologic parameters for prediction of long-term prognosis in CaP.

Isharwal S, Miller MC, Epstein JI, Mangold LA, Humphreys E, Partin AW, Veltri RW. Are you the author?

Int J Cancer. 2008 Sep 2. Epub ahead of print.
doi:10.1002/ijc.23838

Written by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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