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Erschienen in: World Journal of Urology 8/2015

01.08.2015 | Original Article

Multi-institutional validation of the prognostic value of Ki-67 labeling index in patients treated with radical prostatectomy

verfasst von: Romain Mathieu, Shahrokh F. Shariat, Christian Seitz, Pierre I. Karakiewicz, Harun Fajkovic, Maxine Sun, Yair Lotan, Douglas S. Scherr, Ashutosh Tewari, Francesco Montorsi, Alberto Briganti, Morgan Rouprêt, Ilaria Lucca, Vitaly Margulis, Michael Rink, Luis A. Kluth, Malte Rieken, Alexander Bachman, Evanguelos Xylinas, Brian D. Robinson, Karim Bensalah, Markus Margreiter

Erschienen in: World Journal of Urology | Ausgabe 8/2015

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Abstract

Objective

Several smaller single-center studies have reported a prognostic role for Ki-67 labeling index in prostate cancer. Our aim was to test whether Ki-67 is an independent prognostic marker of biochemical recurrence (BCR) in a large international cohort of patients treated with radical prostatectomy (RP).

Methods

Ki-67 immunohistochemical staining on prostatectomy specimens from 3,123 patients who underwent RP for prostate cancer was retrospectively performed. Univariable and multivariable Cox regression models were used to assess the association of Ki-67 status with BCR.

Results

Ki-67 positive status was observed in 762 (24.4 %) patients and was associated with lymph node involvement (LNI) (p = 0.039). Six hundred and twenty-one (19.9 %) patients experienced BCR. The estimated 3-year biochemical-free survivals were 85 % for patients with negative Ki-67 status and 82.1 % for patients with positive Ki-67 status (log-rank test, p = 0.014). In multivariable analysis that adjusted for the effects of age, preoperative PSA, RP Gleason sum, seminal vesicle invasion, extracapsular extension, positive surgical margins, lymphovascular invasion, and LNI, Ki-67 was significantly associated with BCR (HR = 1.19; p = 0.019). Subgroup analysis revealed that Ki-67 is associated with BCR in patients without LNI (p = 0.004), those with RP Gleason sum 7 (p = 0.015), and those with negative surgical margins (p = 0.047).

Conclusion

We confirmed Ki-67 as an independent predictor of BCR after RP. Ki-67 could be particularly informative in patients with favorable pathologic characteristics to help in the clinical decision-making regarding adjuvant therapy and optimized follow-up scheduling.
Literatur
1.
Zurück zum Zitat Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T et al (2014) EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol 65(1):124–137PubMedCrossRef Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T et al (2014) EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol 65(1):124–137PubMedCrossRef
2.
Zurück zum Zitat Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133(4):1710–1715PubMed Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133(4):1710–1715PubMed
3.
Zurück zum Zitat Kristiansen G (2012) Diagnostic and prognostic molecular biomarkers for prostate cancer. Histopathology 60(1):125–141PubMedCrossRef Kristiansen G (2012) Diagnostic and prognostic molecular biomarkers for prostate cancer. Histopathology 60(1):125–141PubMedCrossRef
4.
Zurück zum Zitat Shariat SF, Canto EI, Kattan MW, Slawin KM (2004) Beyond prostate-specific antigen: new serologic biomarkers for improved diagnosis and management of prostate cancer. Rev Urol 6(2):58–72PubMedCentralPubMed Shariat SF, Canto EI, Kattan MW, Slawin KM (2004) Beyond prostate-specific antigen: new serologic biomarkers for improved diagnosis and management of prostate cancer. Rev Urol 6(2):58–72PubMedCentralPubMed
5.
Zurück zum Zitat Shariat SF, Karam JA, Margulis V, Karakiewicz PI (2008) New blood-based biomarkers for the diagnosis, staging and prognosis of prostate cancer. BJU Int 101(6):675–683PubMedCrossRef Shariat SF, Karam JA, Margulis V, Karakiewicz PI (2008) New blood-based biomarkers for the diagnosis, staging and prognosis of prostate cancer. BJU Int 101(6):675–683PubMedCrossRef
6.
Zurück zum Zitat Wheeler TM, Lebovitz RM (1994) Fresh tissue harvest for research from prostatectomy specimens. Prostate 25(5):274–279PubMedCrossRef Wheeler TM, Lebovitz RM (1994) Fresh tissue harvest for research from prostatectomy specimens. Prostate 25(5):274–279PubMedCrossRef
7.
Zurück zum Zitat Gallee MP, Visser-de Jong E, ten Kate FJ, Schroeder FH, Van der Kwast TH (1989) Monoclonal antibody Ki-67 defined growth fraction in benign prostatic hyperplasia and prostatic cancer. J Urol 142(5):1342–1346PubMed Gallee MP, Visser-de Jong E, ten Kate FJ, Schroeder FH, Van der Kwast TH (1989) Monoclonal antibody Ki-67 defined growth fraction in benign prostatic hyperplasia and prostatic cancer. J Urol 142(5):1342–1346PubMed
8.
Zurück zum Zitat Bubendorf L, Sauter G, Moch H, Schmid HP, Gasser TC, Jordan P et al (1996) Ki67 labelling index: an independent predictor of progression in prostate cancer treated by radical prostatectomy. J Pathol 178(4):437–441PubMedCrossRef Bubendorf L, Sauter G, Moch H, Schmid HP, Gasser TC, Jordan P et al (1996) Ki67 labelling index: an independent predictor of progression in prostate cancer treated by radical prostatectomy. J Pathol 178(4):437–441PubMedCrossRef
9.
Zurück zum Zitat Bettencourt MC, Bauer JJ, Sesterhenn IA, Mostofi FK, McLeod DG, Moul JW (1996) Ki-67 expression is a prognostic marker of prostate cancer recurrence after radical prostatectomy. J Urol 156(3):1064–1068PubMedCrossRef Bettencourt MC, Bauer JJ, Sesterhenn IA, Mostofi FK, McLeod DG, Moul JW (1996) Ki-67 expression is a prognostic marker of prostate cancer recurrence after radical prostatectomy. J Urol 156(3):1064–1068PubMedCrossRef
10.
Zurück zum Zitat Cheng L, Pisansky TM, Sebo TJ, Leibovich BC, Ramnani DM, Weaver AL et al (1999) Cell proliferation in prostate cancer patients with lymph node metastasis: a marker for progression. Clin Cancer Res 5(10):2820–2823PubMed Cheng L, Pisansky TM, Sebo TJ, Leibovich BC, Ramnani DM, Weaver AL et al (1999) Cell proliferation in prostate cancer patients with lymph node metastasis: a marker for progression. Clin Cancer Res 5(10):2820–2823PubMed
11.
Zurück zum Zitat Vis AN, Noordzij MA, Fitoz K, Wildhagen MF, Schroder FH, van der Kwast TH (2000) Prognostic value of cell cycle proteins p27(kip1) and MIB-1, and the cell adhesion protein CD44 s in surgically treated patients with prostate cancer. J Urol 164(6):2156–2161PubMedCrossRef Vis AN, Noordzij MA, Fitoz K, Wildhagen MF, Schroder FH, van der Kwast TH (2000) Prognostic value of cell cycle proteins p27(kip1) and MIB-1, and the cell adhesion protein CD44 s in surgically treated patients with prostate cancer. J Urol 164(6):2156–2161PubMedCrossRef
12.
Zurück zum Zitat Halvorsen OJ, Haukaas S, Hoisaeter PA, Akslen LA (2001) Maximum Ki-67 staining in prostate cancer provides independent prognostic information after radical prostatectomy. Anticancer Res 21(6A):4071–4076PubMed Halvorsen OJ, Haukaas S, Hoisaeter PA, Akslen LA (2001) Maximum Ki-67 staining in prostate cancer provides independent prognostic information after radical prostatectomy. Anticancer Res 21(6A):4071–4076PubMed
13.
Zurück zum Zitat Sebo TJ, Cheville JC, Riehle DL, Lohse CM, Pankratz VS, Myers RP et al (2002) Perineural invasion and MIB-1 positivity in addition to Gleason score are significant preoperative predictors of progression after radical retropubic prostatectomy for prostate cancer. Am J Surg Pathol 26(4):431–439PubMedCrossRef Sebo TJ, Cheville JC, Riehle DL, Lohse CM, Pankratz VS, Myers RP et al (2002) Perineural invasion and MIB-1 positivity in addition to Gleason score are significant preoperative predictors of progression after radical retropubic prostatectomy for prostate cancer. Am J Surg Pathol 26(4):431–439PubMedCrossRef
14.
Zurück zum Zitat Rubin MA, Dunn R, Strawderman M, Pienta KJ (2002) Tissue microarray sampling strategy for prostate cancer biomarker analysis. Am J Surg Pathol 26(3):312–319PubMedCrossRef Rubin MA, Dunn R, Strawderman M, Pienta KJ (2002) Tissue microarray sampling strategy for prostate cancer biomarker analysis. Am J Surg Pathol 26(3):312–319PubMedCrossRef
15.
Zurück zum Zitat Revelos K, Petraki C, Gregorakis A, Scorilas A, Papanastasiou P, Tenta R et al (2005) p27(kip1) and Ki-67 (MIB1) immunohistochemical expression in radical prostatectomy specimens of patients with clinically localized prostate cancer. In Vivo 19(5):911–920PubMed Revelos K, Petraki C, Gregorakis A, Scorilas A, Papanastasiou P, Tenta R et al (2005) p27(kip1) and Ki-67 (MIB1) immunohistochemical expression in radical prostatectomy specimens of patients with clinically localized prostate cancer. In Vivo 19(5):911–920PubMed
16.
Zurück zum Zitat Inoue T, Segawa T, Shiraishi T, Yoshida T, Toda Y, Yamada T et al (2005) Androgen receptor, Ki67, and p53 expression in radical prostatectomy specimens predict treatment failure in Japanese population. Urology 66(2):332–337PubMedCrossRef Inoue T, Segawa T, Shiraishi T, Yoshida T, Toda Y, Yamada T et al (2005) Androgen receptor, Ki67, and p53 expression in radical prostatectomy specimens predict treatment failure in Japanese population. Urology 66(2):332–337PubMedCrossRef
17.
Zurück zum Zitat Rubio J, Ramos D, Lopez-Guerrero JA, Iborra I, Collado A, Solsona E et al (2005) Immunohistochemical expression of Ki-67 antigen, cox-2 and Bax/Bcl-2 in prostate cancer; prognostic value in biopsies and radical prostatectomy specimens. Eur Urol 48(5):745–751PubMedCrossRef Rubio J, Ramos D, Lopez-Guerrero JA, Iborra I, Collado A, Solsona E et al (2005) Immunohistochemical expression of Ki-67 antigen, cox-2 and Bax/Bcl-2 in prostate cancer; prognostic value in biopsies and radical prostatectomy specimens. Eur Urol 48(5):745–751PubMedCrossRef
18.
Zurück zum Zitat Shimizu Y, Segawa T, Inoue T, Shiraishi T, Yoshida T, Toda Y et al (2007) Increased Akt and phosphorylated Akt expression are associated with malignant biological features of prostate cancer in Japanese men. BJU Int 100(3):685–690PubMedCrossRef Shimizu Y, Segawa T, Inoue T, Shiraishi T, Yoshida T, Toda Y et al (2007) Increased Akt and phosphorylated Akt expression are associated with malignant biological features of prostate cancer in Japanese men. BJU Int 100(3):685–690PubMedCrossRef
19.
Zurück zum Zitat Laitinen S, Martikainen PM, Tolonen T, Isola J, Tammela TL, Visakorpi T (2008) EZH2, Ki-67 and MCM7 are prognostic markers in prostatectomy treated patients. Int J Cancer 122(3):595–602PubMedCrossRef Laitinen S, Martikainen PM, Tolonen T, Isola J, Tammela TL, Visakorpi T (2008) EZH2, Ki-67 and MCM7 are prognostic markers in prostatectomy treated patients. Int J Cancer 122(3):595–602PubMedCrossRef
20.
Zurück zum Zitat Goto T, Nguyen BP, Nakano M, Ehara H, Yamamoto N, Deguchi T (2008) Utility of Bcl-2, P53, Ki-67, and caveolin-1 immunostaining in the prediction of biochemical failure after radical prostatectomy in a Japanese population. Urology 72(1):167–171PubMedCrossRef Goto T, Nguyen BP, Nakano M, Ehara H, Yamamoto N, Deguchi T (2008) Utility of Bcl-2, P53, Ki-67, and caveolin-1 immunostaining in the prediction of biochemical failure after radical prostatectomy in a Japanese population. Urology 72(1):167–171PubMedCrossRef
21.
Zurück zum Zitat Gunia S, Albrecht K, Koch S, Herrmann T, Ecke T, Loy V et al (2008) Ki67 staining index and neuroendocrine differentiation aggravate adverse prognostic parameters in prostate cancer and are characterized by negligible inter-observer variability. World J Urol 26(3):243–250PubMedCrossRef Gunia S, Albrecht K, Koch S, Herrmann T, Ecke T, Loy V et al (2008) Ki67 staining index and neuroendocrine differentiation aggravate adverse prognostic parameters in prostate cancer and are characterized by negligible inter-observer variability. World J Urol 26(3):243–250PubMedCrossRef
22.
Zurück zum Zitat Miyake H, Muramaki M, Kurahashi T, Takenaka A, Fujisawa M (2010) Expression of potential molecular markers in prostate cancer: correlation with clinicopathological outcomes in patients undergoing radical prostatectomy. Urol Oncol 28(2):145–151PubMedCrossRef Miyake H, Muramaki M, Kurahashi T, Takenaka A, Fujisawa M (2010) Expression of potential molecular markers in prostate cancer: correlation with clinicopathological outcomes in patients undergoing radical prostatectomy. Urol Oncol 28(2):145–151PubMedCrossRef
23.
Zurück zum Zitat Antonarakis ES, Keizman D, Zhang Z, Gurel B, Lotan TL, Hicks JL et al (2012) An immunohistochemical signature comprising PTEN, MYC, and Ki67 predicts progression in prostate cancer patients receiving adjuvant docetaxel after prostatectomy. Cancer 118(24):6063–6071PubMedCentralPubMedCrossRef Antonarakis ES, Keizman D, Zhang Z, Gurel B, Lotan TL, Hicks JL et al (2012) An immunohistochemical signature comprising PTEN, MYC, and Ki67 predicts progression in prostate cancer patients receiving adjuvant docetaxel after prostatectomy. Cancer 118(24):6063–6071PubMedCentralPubMedCrossRef
24.
Zurück zum Zitat Kachroo N, Gnanapragasam VJ (2013) The role of treatment modality on the utility of predictive tissue biomarkers in clinical prostate cancer: a systematic review. J Cancer Res Clin Oncol 139(1):1–24PubMedCrossRef Kachroo N, Gnanapragasam VJ (2013) The role of treatment modality on the utility of predictive tissue biomarkers in clinical prostate cancer: a systematic review. J Cancer Res Clin Oncol 139(1):1–24PubMedCrossRef
25.
Zurück zum Zitat Zellweger T, Gunther S, Zlobec I, Savic S, Sauter G, Moch H et al (2009) Tumour 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(9):2116–2123PubMedCrossRef Zellweger T, Gunther S, Zlobec I, Savic S, Sauter G, Moch H et al (2009) Tumour 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(9):2116–2123PubMedCrossRef
26.
Zurück zum Zitat Shariat SF (2014) Incorporating biomarker research in a real-world setting: challenges of a prophecy. Urol Oncol 32(3):219–221PubMedCrossRef Shariat SF (2014) Incorporating biomarker research in a real-world setting: challenges of a prophecy. Urol Oncol 32(3):219–221PubMedCrossRef
27.
Zurück zum Zitat D’Amico AV, Whittington R, Malkowicz SB, Cote K, Loffredo M, Schultz D et al (2002) Biochemical outcome after radical prostatectomy or external beam radiation therapy for patients with clinically localized prostate carcinoma in the prostate specific antigen era. Cancer 95(2):281–286PubMedCrossRef D’Amico AV, Whittington R, Malkowicz SB, Cote K, Loffredo M, Schultz D et al (2002) Biochemical outcome after radical prostatectomy or external beam radiation therapy for patients with clinically localized prostate carcinoma in the prostate specific antigen era. Cancer 95(2):281–286PubMedCrossRef
28.
Zurück zum Zitat Verze P, Scuzzarella S, Martina GR, Giummelli P, Cantoni F, Mirone V (2013) Long-term oncological and functional results of extraperitoneal laparoscopic radical prostatectomy: one surgical team’s experience on 1,600 consecutive cases. World J Urol 31(3):529–534PubMedCrossRef Verze P, Scuzzarella S, Martina GR, Giummelli P, Cantoni F, Mirone V (2013) Long-term oncological and functional results of extraperitoneal laparoscopic radical prostatectomy: one surgical team’s experience on 1,600 consecutive cases. World J Urol 31(3):529–534PubMedCrossRef
29.
Zurück zum Zitat Bolton DM, Ta A, Bagnato M, Muller D, Lawrentschuk NL, Severi G et al (2014) Interval to biochemical recurrence following radical prostatectomy does not affect survival in men with low-risk prostate cancer. World J Urol 32(2):431–435PubMedCrossRef Bolton DM, Ta A, Bagnato M, Muller D, Lawrentschuk NL, Severi G et al (2014) Interval to biochemical recurrence following radical prostatectomy does not affect survival in men with low-risk prostate cancer. World J Urol 32(2):431–435PubMedCrossRef
30.
Zurück zum Zitat Bensalah K, Montorsi F, Shariat SF (2007) Challenges of cancer biomarker profiling. Eur Urol 52(6):1601–1609PubMedCrossRef Bensalah K, Montorsi F, Shariat SF (2007) Challenges of cancer biomarker profiling. Eur Urol 52(6):1601–1609PubMedCrossRef
Metadaten
Titel
Multi-institutional validation of the prognostic value of Ki-67 labeling index in patients treated with radical prostatectomy
verfasst von
Romain Mathieu
Shahrokh F. Shariat
Christian Seitz
Pierre I. Karakiewicz
Harun Fajkovic
Maxine Sun
Yair Lotan
Douglas S. Scherr
Ashutosh Tewari
Francesco Montorsi
Alberto Briganti
Morgan Rouprêt
Ilaria Lucca
Vitaly Margulis
Michael Rink
Luis A. Kluth
Malte Rieken
Alexander Bachman
Evanguelos Xylinas
Brian D. Robinson
Karim Bensalah
Markus Margreiter
Publikationsdatum
01.08.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
World Journal of Urology / Ausgabe 8/2015
Print ISSN: 0724-4983
Elektronische ISSN: 1433-8726
DOI
https://doi.org/10.1007/s00345-014-1421-3

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