Prognostische DNA-Zytometrie beim Prostatakarzinom

Zusammenfassung

Der subjektive Gleason-Score (GS) schätzt die Prognose von Patienten mit Prostatakarzinom nicht sicher genug ein, um davon schwerwiegende Entscheidungen über Therapiemaßnahmen abhängig zu machen. In Karzinomen nehmen, bedingt durch chromosomale Instabilität im Rahmen der zytogenetischen Tumorprogression, Ausmaß und Variabilität chromosomaler Aberrationen (Aneuploidie) zu. Damit geht eine zunehmende Malignität der Tumoren einher. Durch Messung des DNA-Gehalts in Hunderten von Tumorzellen aus Stanzbiopsien kann man das Ausmaß der DNA-Aneuploidie als objektives Maß für die Bösartigkeit individueller Karzinome bestimmen. Niedrigrisiko-Karzinome der Prostata zeigen mit den gängigen Messmethoden von gesunden Zellen nicht unterscheidbare, peridiploide DNA-Gehalte. Aufgrund der aktuellen S3-Leitlinien Prostatakarzinom für eine Aktive Überwachung infrage kommende Patienten mit solchen, prognostisch sehr günstigen DNA-Verteilungen können sich dieser Strategie beruhigter anvertrauen als aufgrund eines niedrigen Gleason-Scores < = 6 alleine. Für Patienten mit Prostatakarzinomen höherer DNA-Malignitätsgrade sollten jedoch unmittelbar kurative Ansätze gewählt werden, da ihr Risiko für einen Progress nachweislich erhöht ist.

Summary

Subjective Gleason-Score does not assess the prognosis of prostate cancer patients with sufficient accuracy to make serious decisions on therapeutic strategies dependent from it. In cancer cells the degree and variability of chromosomal aberrations (aneuploidy) often increases due to chromosomal instability. This is accompanied by increasing malignancy. The degree of DNA-aneuploidy as an objective measure of the malignant potential of individual cancers can be assessed by measuring the DNA-content in hundreds to thousands of cancer cells from existing biopsies. Low-risk cancers of the prostate reveal nuclear DNA-contents that cannot be differentiated from those of normal diploid cells. Patients who according to current S3-guilines are suitable for the Active Surveillance strategy and who reveal such prognostical favourable diploid DNA-distributions, can more confidently rely on this strategy than based on a Gleason-Score < = 6 alone. Patients with prostate cancer of higher DNA-grades of malignancy instead should be reccommended for an immediate curative therapy, as their risk of tumor-progression otherwise is too high.

Schlüsselwörter

Prostatakarzinom - Prognose - Gleason-Score - DNA-Zytometrie - DNA-Grading - Aktive Überwachung

Keywords

Prostate cancer - prognosis - Gleason-score - DNA-cytometry - Active Surveillance - DNA-Grading

• Literatur

• 1 Adolfsson J, Rönström L, Hedlund PO et al The prognostic value of modal deoxyribonucleic acid in low grade, low stage untreated prostate cancer. J Urol 1990; 144: 1404-1407
• 2 Ahlgren G, Lindholm K, Falkmer U, Abrahamson PA. DNA-cytometric proliferation index improves the value of the DNA-pattern as a prognosticating tool in patients with carcinoma of the prostate. Urol 1997; 50(3): 379-384
• 3 Alcaraz A, Takahashi S, Brown JA et al Aneuploidy and aneusomy of chromosome 7 detected by fluorescence in situ hybridization are markers of poor prognosis in prostate cancer. Cancer Res 1994; 54: 3998-4002
• 4 Amling CL, Lerner SE, Martin SL et al Deoxiribonucleic acid ploidy and serum prostate specific antigen predict outcome following salvage prostatectomy for radiation refractory prostate cancer. J Urol 1999; 161: 857-863
• 5 Bangma, CH. Roemeling S, Schröder FH. Overdiagnosis and overtreatment of early detected prostate cancer. Word J Urol 2007; 25: 3-9
• 6 Bangma CH, Bul M, van der Kwaast TH et al Active surveillance for low risk prostate cancer Crit Rev Oncol/Hematol 2012; https//dx.dol.org/10.1016/j.critrevonc.2012.07.005
• 7 Bantis A, Gonidi M, Athanassiadis P et al Prognostic value of DNA-analysis of prostate adenocarcinoma: Correlation to clinicopathologic predictors. J Exper Clin Cancer Res 2005; 24(2): 273-278
• 8 Baretton GB, Valina C, Schneidenbanger TVK et al Interphase cytogenetic analysis of prostatic carcinoma by use of nonisotopic in situ hybridization. Cancer Res 1994; 54: 4472-4480
• 9 Böcking A, Giroud F, Reith A. Consensus report of the ESACP task force on standardization of diagnostic DNA image cytometry. Analyt Cell Pathol 1995; 8: 67-74
• 10 Böcking A, Tils M, Biesterfeld S. DNA-cytometric grading the malignancy of cancer. Review of the literature. Submitted for publication in: Pathology Discovery, October 2013
• 11 Blute ML, Nativ O, Zincke H et al Pattern of failure after radical retropubic prostatectomy for clinically and pathologically localized adenocarcinoma of the prostate: influence of tumor deoxiribonucleic acid ploidy. J Urol 1989; 142: 1262-1265
• 12 Borre BM, Hoyer M, Nerstrom B, Overgaard J. DNA-ploidy and survival of patients with clinically localized prostate cancer treated without intent to cure. Prostate 1998; 36(4): 244-249
• 13 Buhmeida A, Pyrhönen S, Laato M, Collan Y. Prognostic factors in prostate cancer. Diagn Pathol 2006; 1:4, www.diagnosticpathology.org/content/1/1/4
• 14 Burchardt M, Engers R, Müller M et al Interobserver reproducibility of Gleason grading: evaluation using prostate cancer tissue microarrays. J Cancer Res Clin Oncol 2008; 134: 1071-1078
• 15 Centeno BA, Zietman AL, Shipley WU et al Flow cytometric analysis of DNA ploidy, percent S-phase fraction, and total proliferative fraction as prognostic indicators of local control and survival following radiation therapy for prostate carcinoma. Int J Rad Oncol Biol Phys 1994; 2: 309-315
• 16 Chakravanti A, Zhai GG. Molecular and genetic prognostic factors of prostate cancer. World J Urol 2003; 21: 265-274
• 17 Czeloth K, Albers P. „Active surveillance“ des lokalisierten Prostatakarzinoms. Onkologe 2007; 13: 691-700
• 18 Deutsche Gesellschaft für Urologie Interdisziplinäre Leitlinie der Qualität S3 zur Früherkennung, Diagnose und Therapie der verschiedenen Stadien des Prostatakarzinoms 2011; Version 2.0
• 19 Deliveliotis C, Skolarikos A, Karayannis A et al The prognostic value of p53 and DNA ploidy following radical prostatectomy. World J Urol 2003; 21: 171-176
• 20 Duesberg P. Das Chaos in den Chromosomen. Spektrum der Wissenschaft 2007; Oct 54-64
• 21 Duesberg P, Mandrioli D, McCormack A, Nicholson M. Is carcinogenesis a form of speciation?. Cell Cycle 2011; 10(13): 2100-2114
• 22 Duesberg P, Iacobuzio-Donahue C, Brosnan JA et al Origin of metastases. Subspecies of cancers generated by intrinsic karyotypic variations. Cell Cycle 2012; 11(6): 1151-1166
• 23 Duesberg P, McCormack A. Immortality of cancers. A consequence of inherent karyotypic variations and selections for autonomy. Cell Cycle 2013; 12(5): 783-802
• 24 Engelhard M. Kinetiken des Prostata Spezifischen Antigens als Indikationsstellung zur Prostatastanzbiopsie. [Med. Diss.] Düsseldorf: Universität Düsseldorf; 2013
• 25 Epstein JI, Amin M, Boccon-Gibot L et al Prognostic factors and reporting of prostate carcinoma in radical prostatectomy and pelvic lymphadenectomy specimens. Sand J Urol Nephrol Suppl 2005; 216: 34-63
• 26 Eskelinen M, Lipponen P, Majapuro R et al DNA ploidy, S phase fraction and G2 fraction as prognostic determinants in prostatic adenocarcinoma. Eur Urol 1991; 20: 62-66
• 27 Friedrich D, Chen J, Zhang Y, Demin C, Yuan L, Berynskyy L, Biesterfeld S, Aach T, Böcking A. Identification of Prostate Cancer Cell Nuclei for DNA-Grading of Malignancy. In: Tolxdorff T, et al., eds. Bildverarbeitung für die Medizin 2012. Berlin, Heidelberg: Springer; 2012: 334-339
• 28 Forsslund G, Nilsson B, Zetterberg A. Near tetraploid prostate carcinoma − Methodologic and prognostic aspects. Cancer 1996; 78(8): 1748-1755
• 29 Frankfurt OS, Chin JL, Englander LS et al Relationship between DNA ploidy, glandular diffferentiation, and tumor spread in human prostate cancer. Cancer Res 1985; 45: 1418-1423
• 30 Haroske G, Baak JPA, Danielsen H et al Fourth updated ESACP consensus report on diagnostic DNA image cytometry. Anal Cell Pathol 2001; 23: 89-95
• 31 HAROW-Zwischenbericht 2011 der Stiftung Männergesundheit. Berlin: Clinische Studien Gesellschaft mbH; 2011
• 32 Isharwal S, Miller MC, Epstein JI et al DNA ploidy as surrogate for biopsy Gleason score for preoperative organ versus nonorgan-confined prostate cancer prediction. Urol 2009; 73(5): 1092-1097
• 33 Keyes M, MacAulay C, Hayes M et al DNA ploidy measured on archived pre-treatment biopsy material may correlate with PSA recurrence after prostate brachytherapy. Int J Rad Oncol Biol Phys 2013; 86(5): 829-34
• 34 Klotz L, Zhang L, Lam A et al Clinical results of long-term follow-up of a large, active surveillance cohort with localized prostate cancer. J Clin Oncol 2010; 28(1): 126-131
• 35 Matsuyama H, Pan Y, Oba K et al The role of chromosome 8p22 detection for predicting progression and pathologic staging in prostate Cancer. Aktuelle Urol 2003; 34(49): 247-249
• 36 Martínez JabaloyasJM, Jiménez-Sánchez A, Ruiz CerdáJL et al Valor pronóstico de la ploidía del ADN y la morfometría nuclear en el cáncer de próstata metastásico. Act Urol Espa 2004; 28(4): 298-307
• 37 Milcent S, Lorenzato M, Enaschescu D et al La ploїdie cellulaire: facteur prédictif de cancer de prostate localement avancé. Progr Urol 2007; 17: 819-823
• 38 Miller GJ, Brawer MK, Sakr WA et al Prostate cancer: serum and tissue markers. Rev Urol 2001; 3: 11-19
• 39 Mitelman database. 2011 http://library.uthsscsa.edu/2011/10/mitelman-database-of-chromosomal-aberrations-in-cancer/
• 40 Mohler JL, Williams BT, Freeman JA. Expectant management as an option for men with stage T1c prostate cancer: a prelininary study. Word J Urol 1997; 15: 364-68
• 41 Montironi R, Mazzucchelli R, Scarpelli M et al Prostate carcinoma II: prognostic factors in prostate needle biopsies. Brit J Urol Int 2006; 97: 492-497
• 42 Nativ O, Winkler HZ, Raz Y et al Stage C prostatic adenocarcinoma: Flow cytometric nuclear DNA ploidy analysis. Mayo Clin Proc 1989; 64: 911-919
• 43 Netto GJ, Eisenberger M, Epstein JI. Interobserver variability in histologic evaluation of ratdical prostatectomy between central and local pathologists: Findings of TAY 3501 multinational clinical trial. J Urol 2011; 77: 1155-1160
• 44 Otabi M, Ross P et al Role of repeated biopsy of the prostaet in predicting disease progression i patients with prostae cancer on anctive surveillance. Cancer 2008; 113: 286-292
• 45 Philips JL, Hayward SW, Wang Y et al The consequences of chromosomal aneuploidy on gene expression in a cell line model for prostate carcinogenesis. Cancer Res 2001; 61(8): 8143-8149
• 46 Pretorius ME, Waehre H, Abeler VM et al Large scale genomic instability as an additive prognostic marker in early prostate cancer. Cell Oncol 2009; 31: 251-259
• 47 Roemeling S, Roobol MJ, de Vries S et al Actice surveillance for prostate cancers detected in three subsequent rounds of a screening trial: characteristics, PSA-doubling time and outcome. Eur Urol 2007; 51: 1244-1251
• 48 Ross JS, Figge H, Bui HX et al Prediction of pathologic stage and postprostatectomy disease recurrence by DNA ploidy analysis of initial needle biopsy specimens of prostate cancer. Cancer 1994; 74(10): 2811-2818
• 49 Ross JS, Sheehan CE, Ambros RA et al Needle biopsy DNA ploidy status predicts grade shifting in prostate cancer. Am J Surg Pathol 1999; 23(3): 296-301
• 50 Stephenson RA, James BC, Gay H et al Flow cytometry of prostate cancer: Relationship of DNA content to survival. Cancer Res 1987; 47: 2504-2507
• 51 Tils M. Häufigkeit von DNA-Ploidiemustern in Stanzbiopsien vom Prostatakarzinom. [Med. Diss.] Düsseldorf: Universität Düsseldorf; 2013
• 52 Tribukait B. DNA-Flow-cytometry in carcinoma of the prostate for diagnosis, prognosis and study of tumor biology. Acta Oncol 1991; 30: 187-193
• 53 Tribukait B. Nuclear deoxyribonucleic acid determination in patients with prostate carcinomas: Clinical research and application. Europ Urol 1993; 23(2): 64-76
• 54 Tribukait B. Klinische Bedeutung der DNA-Durchflusszytometrie beim Prostatakarzinom. In: Samsel W, Böcking A, eds Prognostische und therapeutische Bedeutung der DNA-Zytometrie beim Prostatakarzinom. Schriftenreihe zur Gesundheitsanalyse, Bd. 41. St. Augustin: Asgard; 115-133
• 55 Veloso SG, Lima MF, Salles PG et al Interobserver agreement of Gleason score and modified Gleason score in needle biopsy and in surgical specimen of prostate cancer. Clin Urol 2007; 33(5): 639-651
• 56 Vesalainen S, Nordling S, Lipponen P et al Progression and survival in prostatic adenocarcinoma: a comparison of clinical stage, Gleason grade, S-phase fraction and DNA ploidy. Brit J Cancer 1994; 70: 309-314
• 57 Welch HG, Black WC. Overdiagnosis in cancer. J Natl Cancer Inst 2010; 102(9): 605-613
• 58 Winkler HZ, Rainwater LM, Myers RP et al Stage D1 prostatic adenocarcinoma: Significance of nuclear DNA ploidy patterns studied by flow cytometry. Mayo Clin Proc 1988; 63: 103-112