Zusammenfassung
Die Tritium-markierte Thymidin-Histoautoradiographie, die versilberbare Nukleolen organisierenden Regionen (AgNOR-Technik) und die Ki67-MIB-1-Immunhistochemie haben zellkinetisch die Prostatakarzinomentwicklung in gering, mäßig und stark proliferierende Tumoren unterteilt, sich neben der klassischen Histologie und Zytologie als wichtige Zusatzmethoden gezeigt und Vorlagen für das Grading mit „low“, „intermediate“ und „high grade“ geliefert. Die DNA-Zytometrie kann durch den Nachweis mehrheitlich diploider oder aneuploider Zellkerne die Zellkinetik des Prostatakarzinoms (PCa) stützen, sollte aber nur zusammen mit der Histologie bewertet werden. Alle auf der Histologie basierenden zellkinetischen Analysen schließen die klassischen sowohl hoch als auch niedrig differenzierten glandulären und kribriformen sowie soliden undifferenzierten Strukturen und ihre Unterformen ein, sodass der Malignitätsgrad ein Summationsgrad sein kann, sofern die genannten Untersuchungen in das Grading mit einbezogen werden. Die Zukunftsperspektiven einer individualisierten Therapieoption, z. B. bei der „active surveillance“ für das Low-grade-PCa, aber auch für die höhergradigen PCa, liegen in den molekularen Zusatzmethoden einschließlich gesamtgenomischen Untersuchungen mithilfe des „next generation sequencing“.
Abstract
Using tritium-labeled thymidine histoautoradiography, the AgNOR staining technique and Ki67-MIB-1 immunohistochemistry to study cell kinetics, prostate cancer can be subdivided into slowly, moderately and rapidly proliferating tumors. These are important supplementary methods and prerequisites for a grading as low, intermediate and high-grade in addition to classical histology and cytology. Cytometry of DNA can confirm the cell kinetics of prostate cancer by detection of a predominance of diploid or aneuploid cell nuclei but should only be evaluated together with histological investigations. All histology-based analyses of cell kinetics encompass the classical highly and poorly differentiated glandular and cribriform patterns as well as solid undifferentiated structures and the various subcategories. The malignancy grading of prostate cancer can result from the summation of histological grading and cell kinetic analyses, as long as the named investigations are included. The future perspectives of individualized therapy options, including active surveillance in early low-grade and also for high-grade prostate cancer and new antihormonal treatment in advanced disease, may increasingly rely on tissue biomarkers and advanced technologies for whole genome analysis including next generation sequencing.
Literatur
Adolfsson J, Tribukait B, Levitt S (2007) The 20-yr outcome in patients with well- or moderately differentiated clinically localized prostate cancer diagnosed in the pre-PSA era: the prognostic value of tumour ploidy and comorbidity. Eur Urol 52:1028–1035
Barrett MT, Lenkiewicz E, Evers L, Holley T, Ruiz C, Bubendorf L, Sekulic A, Ramanathan R, von Hoff DD (2013) Clonal evolution and therapeutic resistance in solid tumors. Front Pharmacol 4:1–15
Böcking A, Dietz J (2013) Prognostische DNA-Zytometrie beim Prostatakarzinom. Dtsch Z Onkol 45:2–8
Böcking A, Chatelain R, Orthen U, Gien G, von Kalckreuth G, Jocham D, Wohltmann D (1988) DNA-grading of prostatic carcinoma: prognostic validity and reproducibility. Anticancer Res 8:129–135
Böcking A, Tils M, Schramm M, Dietz J, Biesterfeld S (2014) DNA-cytometric grading of prostate cancer. Systematic review with descriptive data analysis. Pathol Discov 2(7):1–20 (ISSN 2052-7896)
Böcking A, Biesterfeld S, Dietz J et al (2015) Objektive DNA-Malignitätsgradierung als Ergänzung zum histologischen Gleason-Score. Frankfurter Konsens. Pathologe 36:498–502
Bonkhoff H (1996) Role of the basal cells in premalignant changes of the human prostate: a stem cell concept for the development of prostate cancer. Eur Urol 30:201–205
Bubendorf L, Sauter G, Moch H et al (1996) Prognostic significance of Bcl-2 in clinically localized prostate cancer. Am J Pathol 148:1557–1565
Deliveliotis C, Skolarikos A, Karayannis A, Tzelepis V, Trakas N, Alargof E, Protogerou V (2003) The prognostic value of p53 and DNA ploidy following radical prostatectomy. World J Urol 21:171–176
Epstein JI, Zelefsky MJ, Sjoberg DD (2015) A contemporary prostate cancer grading system: a validated alternative to the Gleason score. Eur Urol. doi:10.1016/eururo 2015.06.0469
Epstein JI, Egevad L, Amin MB et al (2015) The 2014 International Society of Urological Pathology (ISUP) consensus conference opn Gleason grading of prostatic carcinoma: definition of grading patterns and proposal for a new grading system. Am J Surg Pathol (PMID: 26492179)
Fox DT, Duronio RJ (2013) Endoreplication and polyploidy: recent insights into development and disease. Development 140:3–12
Gundem G, Van Loo P, Kremeyer B et al (2015) The evolutionary history of lethal metastatic prostate cancer. Nature 520:353–357
Haffner MC, Mosbruger T, Esopi DM (2013) Tracking the clonal origin of lethal prostate cancer. J Clin Invest 123:4918–4922
Häggarth L, Auer G, Busch C, Norberg M, Häggman M, Egevad L (2005) The significance of tumor heterogeneity for prediction of DNA ploidy of prostate cancer. Scand J Urol Nephrol 39:387–392
Heidenreich A, Bastian PJ, Bellmunt J et al (2014) EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol 65:124–137
Helpap B (1980) The biological significance of atypical hyperplasia of the prostate. Virchows Arch A Path Anat Histol 387:307–317
Helpap B (1981) Cell kinetic and cytological grading of prostatic carcinoma. Virchows Arch A Pathol Anat Histol 393:205–214
Helpap B (1988) Frequency and localization of nucleoli in nuclei from prostatic carcinoma and atypical hyperplasia. Histopathology 13:203–211
Helpap B (1993) Review of the morphology of prostatic carcinoma with special emphasis on subgrading and prognosis. J Urol Pathol 1:3–20
Helpap B (1995) Cell kinetic studies on prostatic intraepithelial neoplasia (PIN) and atypical adenomatous hyperplasia (AAH) of the prostate. Pathol Res Pract 191:904–907
Helpap B, Kristiansen G (2016) Prostata und Samenblasen. In: Amann K, Kain R, Klöppel G (Hrsg) Pathologie. Urogenitale und Endokrine Organe, Gelenke und Skelett. Springer, Berlin, S 139–194
Helpap B, Maurer W (1969) Autoradiographische Untersuchungen zur Frage der Vergleichbarkeit des Einbaus von markiertem Thymidin unter in vivo-Bedingungen und bei Inkubation von Gewebsproben. Virchows Arch Abt B 4:102–118
Helpap B, Riede C (1995) Nucleolar organizer regions in low- and high-grade carcinomas of the prostate. World J Urol 13:195–199
Helpap B, Riede C (1995) Nucleolar and AgNOR analysis of prostatic intraepithelial neoplasia (PIN), atypical adenomatous hyperplasia (AAH) and prostatic carcinoma. Pathol Res Pract 191:381–390
Helpap B, Stiens R, Brühl P (1974) Autoradiographische Untersuchungen an inkubierten Prostatapunktaten nach Doppelmarkierung mit C-14 und H-3-Thymidin. Beitr Pathol 151:65–74
Helpap B, Ringli D, Breul J, Tonhauser J, Poser I, Seifert HH (2015) The value of prognostic grouping of prostatic carcinomas for urologists and pathologists. Urol Int. 95:436–444
Jhavar S, Bartlett J, Kovacs G et al (2009) Biopsy tissue microarray study of Ki-67 expression in untreated, localized prostate cancer managed by active surveillance. Prostate Cancer Prostatic Dis 12:143–147
Kastendieck H (1977) Ultrastruktur-Pathologie der menschlichen Prostatatadrüse. Prog Pathol 106:1–167
Kristiansen G (2012) Diagnostic and prognostic molecular biomarkers for prostate cancer. Histopathology 60:125–141
Kristiansen G, Egevad L, Amin MB et al (2016) Die Konsensuskonferenz 2014 der internationalen Gesellschaft für Urologische Pathologie (ISUP) zur Gleasongraduierung des Prostatakarzinoms. Pathologe 37 doi:10.1007/s00292-015-0136-6
Lorenzato M, Rey A, Durlach A, Bouttens D, Birembaut P, Staerman F (2004) DNA image cytometry on biopsies can help the detection of localized Gleason 3 + 3 Prostate cancers. J Urol 172:1311–1313
Mucci NR, Rubin MA, Strawderman MS et al (2000) Expression of nuclear antigen Ki-67 in prostate cancer needle biopsy and radical prostatectomy specimens. J Natl Cancer Inst 92:1941–1946
Pretorius ME, Waehre H, Abeler VM, Davidson B, Vlatkovic L, Lothe RA, Giercksky K-E, Danielsen HE (2009) Large scale genomic instability as an additive prognostic marker in early prostate cancer. Cell Oncol 31:251–259
Ross AE, D’Amico AV, Freedland SJ (2015) Which, when and why? Rational use of tissue based molecular testing in localized prostate camncer. Prostate Cancer Prostatic Dis. doi:10.1038/pcan. 2015.31
Ross JS, Sheehan C, Ambros RA, Nazeer T, Jennings T, Kaufman RP Jr, Fisher H, Rifkin MD, Kallakury BV (1999) Needle biopsy DNA ploidy status predicts grade shifting in prostate cancer. Am J Surg Pathol 23:296–301
Sesterhenn IA, Becker RL, Avallone FA, Mostofi FK, Lin TH, Davis CL Jr (1991) Image analysis of nucleoli and nucleolar organizer regions in prostatic hyperplasia, intraepithelial neoplasia and prostatic carcinoma. Urogenit Pathol 1:61–75
Sommariva S, Tarricone R, Lazzeri M et al (2014) Prognostic value of the cell cycle progression score in patients with prostate cancer: a systematic review and meta-analysis. Eur Urol. doi:10.1016/j eururo 2014.11.038 (PMID: 25481455)
Stepan A, Simionescu C, Pirici D et al (2015) Fractal analysis and the diagnostic usefulness of silver staining nucleolar organizer regions in prostate adenocarcinoma. Anal Cell Pathol (Amst). doi:Org/10.1155/20/2015/250265
Tollefson MK, Kames RJ, Kwon ED, Lohse CM, Rangel LJ, Mynderse LA, Cheville JC, Sebo TJ (2014) Prostate Cancer Ki-67 (MIB-1) expression, perineural invasion, and Gleason score as biopsy-based predictors of prostate cancer mortality: the Mayo model. Mayo Clin Proc 89:306–318
Van der Kwast TH (2014) Prognostic prostate tissue biomarkers of potential clinical use. Virchows Arch 464:293–300
Vogel J, Helpap B (1986) Vergleichende histologisch-zytologische, autoradiographische und immunhistochemische Untersuchungen an Prostatakarzinomen. Verh Dtsch Ges Pathol 70:332–338
Zellweger T, Günther S, Zlobec I, Savic S et al (2009) Tumor growth fraction measured by immunohistochemical staining of Ki67 is an independent prognostic factor in preoperative prostate biopsies with small-volume or low-grade prostate cancer. Int J Cancer 124:2116–2123
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Interessenkonflikt
B. Helpap und L. Bubendorf geben an, dass kein Interessenkonflikt besteht.
Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.
Additional information
Schwerpunktherausgeber
A. Hartmann, Erlangen
R. Knüchel-Clarke, Aachen
G. Kristiansen, Bonn
Rights and permissions
About this article
Cite this article
Helpap, B., Bubendorf, L. Prostatakarzinom. Pathologe 37, 3–10 (2016). https://doi.org/10.1007/s00292-015-0123-y
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00292-015-0123-y