Abstract 2236: Nuclear roundness variance predicts prostate cancer progression, metastasis and death: A prospective evaluation with up to 25 years of follow-up after radical prostatectomy

Abstract

Abstract Introduction and Objective: Nuclear structure is often altered in cancer due to spatial rearrangements of chromatin organization via activation of oncogenes and other chromatin remodeling genes. Therefore, we evaluated the prognostic value of nuclear roundness variance (NRV) for prostate cancer (PCa) progression, metastasis and PCa-specific death-free survivals in a cohort of 116 men after radical prostatectomy (RP). Methods: For each patient, ∼150 intact nuclei from the primary tumor were captured using the DynaCELL Motility Morphometry Measurement workstation (JAW Associates, Inc., Annapolis, MD) at a magnification of 1250X in 1992-93. Next, nuclear roundness variance (NRV) was calculated for each of the 116 cases using the this unique shape factor from ∼150 nuclei captured. The resulting variance values were multiplied by 10,000 to determine the NRV factor for each case. NRV data was merged with clinical, pathologic and follow-up data for all patients in 2009. Cox proportional hazards regression was used to identify significant prognostic factors for prediction of progression, metastasis and PCa-specific death free survivals. Results: Median follow-up time after RP for all patients was 19.0 years (range: 1-25 years, mean: 17.43 years), with approximately 92% (107/116), 71% (82/116) and 47% (55/116) patients having ≥10 years, 15 years and 20 years of follow-up respectively. NRV was the most significant parameter for prediction of all three outcomes and its concordance-index (C-Index) increased from progression (0.7080) to metastasis (0.7332) to PCa-specific death (0.8090) free survival predictions. Of note, NRV C-Index was significantly higher compared to Gleason Score C-Index for metastasis (0.7332 vs. 0.6046; p = 0.027) and PCa-specific death (0.8090 vs. 0.6336; p = 0.004) free survival predictions. However the difference between NRV and Gleason Score C-Indexes was not statistically significant for progression free survival prediction (0.7080 vs. 0.6463; p = 0.106). Conclusions: Variance of nuclear roundness (a measure of tumor heterogeneity) is a valuable nuclear structural feature to assess an aggressive phenotype of prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2236.