Long-term Assessment of Prostate Cancer Progression Free Survival: Evaluation of Pathological Parameters, Nuclear Shape and Molecular Biomarkers of Pathogenesis

Overview

Journal Prostate

Date 2008 Sep 4

PMID 18767028

Citations 11

Authors

Robert W Veltri

Sumit Isharwal

M Craig Miller

Jonathan I Epstein

Leslie A Mangold

Elizabeth Humphreys

Alan W Partin

Affiliations

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Abstract

Background: Molecular pathways of proliferation, angiogenesis, neuroendocrine differentiation, apoptosis and alterations in nuclear structure of cancer epithelial cells are important in the pathogenesis of prostate cancer (PCa). Therefore, we evaluated the prognostic value of these parameters in 105 clinically localized PCa tumors with long-term follow-up after radical prostatectomy for progression-free survival (PFS).

Method: Nuclear roundness variance (NRV) was calculated for tumor nuclei using the graphic tracing DynaCELL system. Immunohistochemistry assessed expression of Ki67, PCNA (proliferation), Chromogranin A (neuroendocrine differentiation), CD31 (angiogenesis), BCL2 (apoptosis), and Her-2/neu (oncogene) in the tumors. Cox proportional hazards regression, Spearman's rank correlation, and Kaplan-Meier plots were employed to analyze the data.

Results: Gleason score, focal vs. non-focal extra-prostatic extension, organ confined status, NRV, Her-2/neu, CD-31 and Ki67 were univariately significant predictors of PFS. NRV was the most significant prognostic indicator with the highest concordance index (0.7) for PFS. Gleason score, NRV and Her-2/neu were multivariately significant and yielded a concordance index of 0.77.

Conclusion: Her-2/neu oncogene and NRV were shown to be significant in the prediction of PFS. The assessment of alterations in nuclear structure using NRV proved to be the most significant factor in the prediction of PFS. Integration of image analysis-based NRV and molecular biomarkers with pathologic parameters should be considered for validation in the prediction of PFS.

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References

Tricoli J, Schoenfeldt M, Conley B . Detection of prostate cancer and predicting progression: current and future diagnostic markers. Clin Cancer Res. 2004; 10(12 Pt 1):3943-53. DOI: 10.1158/1078-0432.CCR-03-0200. View

Calvo B, Levine A, Marcos M, Collins Q, Iacocca M, Caskey L . Human epidermal receptor-2 expression in prostate cancer. Clin Cancer Res. 2003; 9(3):1087-97. View

Veltri R, Miller M, Isharwal S, Marlow C, Makarov D, Partin A . Prediction of prostate-specific antigen recurrence in men with long-term follow-up postprostatectomy using quantitative nuclear morphometry. Cancer Epidemiol Biomarkers Prev. 2008; 17(1):102-10. DOI: 10.1158/1055-9965.EPI-07-0175. View

Gettman M, Bergstralh E, Blute M, Zincke H, Bostwick D . Prediction of patient outcome in pathologic stage T2 adenocarcinoma of the prostate: lack of significance for microvessel density analysis. Urology. 1998; 51(1):79-85. DOI: 10.1016/s0090-4295(97)00464-0. View

Signoretti S, Montironi R, Manola J, Altimari A, Tam C, Bubley G . Her-2-neu expression and progression toward androgen independence in human prostate cancer. J Natl Cancer Inst. 2000; 92(23):1918-25. DOI: 10.1093/jnci/92.23.1918. View

di SantAgnese P . Neuroendocrine differentiation in carcinoma of the prostate. Diagnostic, prognostic, and therapeutic implications. Cancer. 1992; 70(1 Suppl):254-68. DOI: 10.1002/1097-0142(19920701)70:1+<254::aid-cncr2820701312>3.0.co;2-e. View

Osman I, Mikhail M, Shuch B, Clute M, Cheli C, Ghani F . Serum levels of shed Her2/neu protein in men with prostate cancer correlate with disease progression. J Urol. 2005; 174(6):2174-7. DOI: 10.1097/01.ju.0000181205.23233.65. View

Stackhouse G, Sesterhenn I, Bauer J, Mostofi F, Connelly R, Srivastava S . p53 and bcl-2 immunohistochemistry in pretreatment prostate needle biopsies to predict recurrence of prostate cancer after radical prostatectomy. J Urol. 1999; 162(6):2040-5. DOI: 10.1016/S0022-5347(05)68095-0. View

Silberman M, Partin A, Veltri R, Epstein J . Tumor angiogenesis correlates with progression after radical prostatectomy but not with pathologic stage in Gleason sum 5 to 7 adenocarcinoma of the prostate. Cancer. 1997; 79(4):772-9. DOI: 10.1002/(sici)1097-0142(19970215)79:4<772::aid-cncr14>3.0.co;2-x. View

10.

Nelson W, DeWeese T, DeMarzo A . The diet, prostate inflammation, and the development of prostate cancer. Cancer Metastasis Rev. 2002; 21(1):3-16. DOI: 10.1023/a:1020110718701. View

11.

Berruti A, Mosca A, Porpiglia F, Bollito E, Tucci M, Vana F . Chromogranin A expression in patients with hormone naïve prostate cancer predicts the development of hormone refractory disease. J Urol. 2007; 178(3 Pt 1):838-43. DOI: 10.1016/j.juro.2007.05.018. View

12.

Cher M, Chew K, Rosenau W, Carroll P . Cellular proliferation in prostatic adenocarcinoma as assessed by bromodeoxyuridine uptake and Ki-67 and PCNA expression. Prostate. 1995; 26(2):87-93. DOI: 10.1002/pros.2990260205. View

13.

Domingo-Domenech J, Fernandez P, Filella X, Martinez-Fernandez A, Molina R, Fernandez E . Serum HER2 extracellular domain predicts an aggressive clinical outcome and biological PSA response in hormone-independent prostate cancer patients treated with docetaxel. Ann Oncol. 2007; 19(2):269-75. DOI: 10.1093/annonc/mdm490. View

14.

Ahlegren G, Pedersen K, Lundberg S, Aus G, Hugosson J, Abrahamsson P . Neuroendocrine differentiation is not prognostic of failure after radical prostatectomy but correlates with tumor volume. Urology. 2000; 56(6):1011-5. DOI: 10.1016/s0090-4295(00)00838-4. View

15.

Slamon D, Clark G, Wong S, Levin W, Ullrich A, McGuire W . Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987; 235(4785):177-82. DOI: 10.1126/science.3798106. View

16.

Savinainen K, Saramaki O, Linja M, Bratt O, Tammela T, Isola J . Expression and gene copy number analysis of ERBB2 oncogene in prostate cancer. Am J Pathol. 2002; 160(1):339-45. PMC: 1867117. DOI: 10.1016/S0002-9440(10)64377-5. View

17.

Partin A, Walsh A, Pitcock R, Mohler J, Epstein J, Coffey D . A comparison of nuclear morphometry and Gleason grade as a predictor of prognosis in stage A2 prostate cancer: a critical analysis. J Urol. 1989; 142(5):1254-8. DOI: 10.1016/s0022-5347(17)39049-3. View

18.

Albertsen P, Hanley J, Fine J . 20-year outcomes following conservative management of clinically localized prostate cancer. JAMA. 2005; 293(17):2095-101. DOI: 10.1001/jama.293.17.2095. View

19.

Rubin M, Buyyounouski M, Bagiella E, Sharir S, Neugut A, Benson M . Microvessel density in prostate cancer: lack of correlation with tumor grade, pathologic stage, and clinical outcome. Urology. 1999; 53(3):542-7. DOI: 10.1016/s0090-4295(98)00561-5. View

20.

Bigler S, Deering R, Brawer M . Comparison of microscopic vascularity in benign and malignant prostate tissue. Hum Pathol. 1993; 24(2):220-6. DOI: 10.1016/0046-8177(93)90304-y. View