Elevated Ki-67 (MIB-1) expression as an independent predictor for unfavorable pathologic outcomes and biochemical recurrence after radical prostatectomy in patients with localized prostate cancer: A propensity score matched study


Autoři: Seok-Soo Byun aff001;  Minseung Lee aff001;  Sung Kyu Hong aff001;  Hakmin Lee aff001
Působiště autorů: Department of Urology, Seoul National University Bundang Hospital, Seongnam, Korea aff001
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0224671

Souhrn

Background

Ki-67 is known to be useful in estimating the fraction of proliferation tumor cells in various malignancies. We tried to investigate clinical association of Ki-67 (MIB-1) expression with the oncological outcomes in patients with localized prostate cancer (PCa) after the radical prostatectomy (RP).

Materials and Methods

We retrospectively analyzed the data of 1,561 patients who underwent RP for localized PCa. According to the propensity score having Ki-67 expression, 183 patients with positive Ki-67 expression were matched to 549 patients without Ki-67 expression. By using multivariate Cox-proportional hazards models and logistic regression tests, the prognostic value of each variable was tested.

Results

After propensity score matching, positive Ki-67 group showed significant worse clinical characteristics and pathologic outcomes than negative Ki-67 group. The multivariate analysis showed that the Ki-67 expression was significantly associated with several adverse pathologic outcomes including higher pathologic stage (p = 0.006), higher grade group (p = 0.005), seminal vesicle invasion (p = 0.036), and positive surgical margin (p = 0.025). The group with Ki-67 expression showed significant worse biochemical recurrence-free survival (p<0.001) than negative Ki-67 group. Subsequent multivariate Cox analyses showed that Ki-67 was independent predictor for BCR after RP (HR 1.549, 95% CI 1.187–2.021, p = 0.001).

Conclusion

In our study, high Ki-67 expression was significantly related with adverse pathological and finally with worse biochemical recurrence-free survival. Further studies are needed to validate the prognostic value of Ki-67 more exactly in PCa patients.

Klíčová slova:

Cancer treatment – Clinical pathology – Prognosis – Prostate cancer – Prostate gland – Radical prostatectomy – Surgical pathology


Zdroje

1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012 Jan-Feb;62(1):10–29. doi: 10.3322/caac.20138 22237781

2. Dall’Era MA, Klotz L. Active surveillance for intermediate-risk prostate cancer. Prostate Cancer Prostatic Dis. Prostate Cancer Prostatic Dis. 2017; 20:1–6. doi: 10.1038/pcan.2016.51 27801900

3. Madu CO, Lu Y. Novel diagnostic biomarkers for prostate cancer. J Cancer. 2010 Oct 6;1:150–77. 20975847

4. Scholzen T, Gerdes J. The Ki‐67 protein: from the known and the unknown. J Cell Physiol. 2000 Mar;182(3):311–22. doi: 10.1002/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9 10653597

5. Bettencourt MC, Bauer JJ, Sesterhenn IA, Mostofi FK, McLeod DG, Moul JW. Ki-67 expression is a prognostic marker of prostate cancer recurrence after radical prostatectomy. J Urol. 1996 Sep;156(3):1064–8. 8709308

6. Goltz D, Montani M, Braun M, Perner S, Wernert N, Jung K, Dietel M, Stephan C, Kristiansen G. Prognostic relevance of proliferation markers (Ki-67, PHH3) within the cross-relation of ERG translocation and androgen receptor expression in prostate cancer. Pathology. 2015 Dec;47(7):629–36. doi: 10.1097/PAT.0000000000000320 26517642

7. Verhoven B, Yan Y, Ritter M, Khor LY, Hammond E, Jones C et al. Ki-67 Is an Independent Predictor of Metastasis and Cause-Specific Mortality for Prostate Cancer Patients Treated on Radiation Therapy Oncology Group (RTOG) 94–08. Int J Radiat Oncol Biol Phys. 2013 Jun 1;86(2):317–23. doi: 10.1016/j.ijrobp.2013.01.016 23474109

8. Verhoven B, Yan Y, Ritter M, Khor LY, Hammond E, Jones C et al. Ki-67 and p53 immunohistochemical expression in prostate carcinoma: An experience from a tertiary care centre of North India. Int J Radiat Oncol Biol Phys. 2013 Jun 1;86(2):317–23. doi: 10.1016/j.ijrobp.2013.01.016 23474109

9. Epstein JI, Allsbrook WC Jr, Amin MB, Egevad LL; ISUP Grading Committee.The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol 2005; 29: 1228. doi: 10.1097/01.pas.0000173646.99337.b1 16096414

10. Greene FL, Page DL, Fleming ID, Fritz G., Charles M, Haller G et al. eds. AJCC Cancer Staging Manual, 6th ed. Philadelphia, PA: Lippincott Raven; 2002:309–316.

11. Gerdes J, Schwab U, Lemke H, Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer. 1983 Jan 15;31(1):13–20. doi: 10.1002/ijc.2910310104 6339421

12. Gerdes J, Lemke H, Baisch H, Wacker H-H, Schwab U, Stein H. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133: 1710–1715. 6206131

13. Nishimukai A, Yagi T, Yanai A, Miyagawa Y, Enomoto Y, Murase K et al. High Ki-67 Expression and Low Progesterone Receptor Expression Could Independently Lead to a Worse Prognosis for Postmenopausal Patients With Estrogen Receptor-Positive and HER2-Negative Breast Cancer. Clin Breast Cancer. 2015 Jun;15(3):204–11. doi: 10.1016/j.clbc.2014.12.007 25600243

14. Inwald EC, Klinkhammer-Schalke M, Hofstädter F, Zeman F, Koller M, Gerstenhauer M et al. Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry. Breast Cancer Res Treat. 2013 Jun;139(2):539–52. doi: 10.1007/s10549-013-2560-8 23674192

15. Warth A, Cortis J, Soltermann A, Meister M, Budczies J, Stenzinger A et al. Tumour cell proliferation (Ki-67) in non-small cell lung cancer: a critical reappraisal of its prognostic role. Br J Cancer. 2014 Sep 9;111(6):1222–9. doi: 10.1038/bjc.2014.402 Epub 2014 Jul 22. 25051406

16. Klöppel G. On the value of Ki-67 in the prognostic grading of pancreatic neuroendocrine neoplasms: an update. (USCAP, 2017) San Antonio, Texas. Accessed 4–10 March 2017

17. Zeng A, Hu Q, Liu Y, Wang Z, Cui X, Li R et al. IDH1/2 mutation status combined with Ki-67 labeling index defines distinct prognostic groups in glioma. Oncotarget. 2015 Oct 6;6(30):30232–8. doi: 10.18632/oncotarget.4920 26338964

18. Saricanbaz I, Karahacioglu E, Ekinci O, Bora H, Kilic D, Akmansu M. Prognostic significance of expression of CD133 and Ki-67 in gastric cancer. Asian Pac J Cancer Prev. 2014;15(19):8215–9. doi: 10.7314/apjcp.2014.15.19.8215 25339008

19. Bettencourt MC, Bauer JJ, Sesterhenn IA, Mostofi FK, McLeod DG, Moul JW. Ki-67 expression is a prognostic marker of prostate cancer recurrence after radical prostatectomy. J Urol. 1996 Sep;156(3):1064–8. 8709308

20. Pollack A, DeSilvio M, Khor LY, Li R, Al-Saleem TI, Hammond ME et al. Ki-67 staining is a strong predictor of distant metastasis and mortality for men with prostate cancer treated with radiotherapy plus androgen deprivation: Radiation Therapy Oncology Group Trial 92–02. J Clin Oncol. 2004 Jun 1;22(11):2133–40. doi: 10.1200/JCO.2004.09.150 15169799

21. Fisher G, Yang ZH, Kudahetti S, Møller H, Scardino P, Cuzick J et al. Prognostic value of Ki-67 for prostate cancer death in a conservatively managed cohort. Br J Cancer. 2013 Feb 5;108(2):271–7. doi: 10.1038/bjc.2012.598 23329234

22. Tretiakova MS, Wei W, Boyer HD, Newcomb LF, Hawley S, Auman H et al. Prognostic value of Ki67 in localized prostate carcinoma: a multi-institutional study of >1000 prostatectomies. Prostate Cancer Prostatic Dis. 2016 Sep;19(3):264–70. doi: 10.1038/pcan.2016.12 27136741

23. Malhotra S, Lapointe J, Salari K, Higgins JP, Ferrari M, Montgomery K et al. A tri-marker proliferation index predicts biochemical recurrence after surgery for prostate cancer. PLoS One. 2011;6(5):e20293 doi: 10.1371/journal.pone.0020293 21629784

24. Fantony JJ, Howard LE, Csizmadi I, Armstrong AJ, Lark AL, Galet C et al. Is Ki67 prognostic for aggressive prostate cancer? A multicenter real-world study. Biomark Med. 2018 Jul;12(7):727–736. doi: 10.2217/bmm-2017-0322 29902938

25. Thomsen LL, Miles DW. Role of nitric oxide in tumour progression: Lessons from human tumours. Cancer Metastasis Rev 1998;17:107–118. 9544426

26. Orucevic A, Bechberger J, Green AM, Shapiro RA, Billiar TR, Lala PK. Nitric-oxide production by murine mammary adenocarcinoma cells promotes tumor-cell invasiveness. Int J Cancer 1999;81:889–896. doi: 10.1002/(sici)1097-0215(19990611)81:6<889::aid-ijc9>3.0.co;2-2 10362135

27. Jadeski LC, Lala PK. Nitric oxide synthase inhibition by N-(G)-nitro-L-arginine methyl ester inhibits tumor-induced angiogenesis in mammary tumors. Am J Pathol 1999;155:1381–1390. doi: 10.1016/S0002-9440(10)65240-6 10514420


Článek vyšel v časopise

PLOS One


2019 Číslo 11
Nejčtenější tento týden