Supplementary online material:
Appendix
Investigators in participating regional cancer registries, research centres and hospital
trusts are listed below. Members of the Transatlantic Prostate Group are designated
by an asterisk.
Thames Cancer Registry: Henrik Møller*, Shirley Bell (deceased), K. Linklater, J.
Ottey V. Fisher; Ashford & St. Peter’s, M. Hall, N. Harvey Hills; Barnet & Chase
Farm, H. Reid; Brighton and Sussex, N. Kirkham, P. Thomas; Bromley, D. Nurse;
Dartford & Gravesham, I. Dickinson, P. Thebe; East & North Hertfordshire, D.
Hanbury, M. Ali-Izzi; Eastbourne, C. Moffatt; Epsom & St. Helier, M. Bailey, L.
Temple; Essex Rivers Healthcare, W. Aung, C. Booth; Frimley Park, B. Montgomery,
P. Denham; Greenwich Healthcare, N. Cetti, P. Pinto; Guy’s & St Thomas’s, A.
Chandra, T. O’Brien; Hammersmith Hospitals, N. Livni; Havering Hospitals, I. Saeed;
Hillingdon, F. Barker, T. Beaven; King’s Healthcare, G. Muir, Z. Khan; Kingston, C.
Jameson; Lewisham, A. Giles; Mayday Healthcare, N. Arsanious, A. Arnaout; The
Medway, E. Boye; Mid Essex Hospitals; Mid Kent, M. Boyle; North West London
Hospitals, M. Jarmulowicz,; Royal Free Hampstead, R. J. Morgan, A. Bates; St
Bartholomew’s and The Royal London Hospitals, F. Chinegwundoh, R. T. D. Oliver*,
D. Berney*; Wolfson Institute of Preventive Medicine, Queen Mary University of
London, J Cuzick*, G.Fisher*, L.Ambroisine*; Institute of Cancer Research, Sutton,
C Cooper*; Royal Surrey County, S. De Sanctis; Southend, M. Chappell; St
1
George’s, London, R. Kirby, C. Corbishley; St Mary’s, London, A. Patel, M. Walker;
West Hertfordshire, J. Crisp, W. Riddle; Worthing & Southlands Hospitals, J. Grant.
Northern & Yorkshire Cancer Registry & Information Service: David Forman *, C.
Storer, C. Bennett, C. Spink; Airedale, I. Appleyard, J. O’Dowd; Hull & East
Yorkshire, J. Hetherington, A. MacDonald; The Leeds Teaching Hospitals, P.
Whelan, P. Quirke, P. Harnden.
Oxford Cancer Intelligence Unit: Monica Roche*, Sandra Edwards, S. Bose, P. Hall;
Heatherwood & Wexham Park, M. Ali, O. Karim; Milton Keynes, E. Walker, S. Jalloh;
Northampton, M. Miller, A. Molyneux; Oxford Radcliffe, S. Brewster, D. Davies;
Royal Berkshire & Battle, P. Malone, C. McCormick; Stoke Mandeville, J. Greenland,
A. Padel
Welsh Cancer Intelligence & Surveillance Unit: John Steward*, Shelagh Reynolds,
Lynda Roberts, Judith Adams; Ceredigion and Mid Wales, J. Edwards, C.G.B.
Simpson; Conwy & Denbighshire, A. Dalton, V. Srinivasan; NE Wales, A. De Bolla,
C. Burdge; Gwent Healthcare, W. Bowsher, M. Rashid; Swansea, M. Lucas, C.
O’Brien; Cardiff & Vale, M. Varma.
Scottish Cancer Registry: David Brewster*; The Lothian University Hospitals,
J.Royle, K.Grigor; North Glasgow University Hospitals, D.Kirk, A Milano, R.Reid.
Merseyside & Cheshire Cancer Registry: Lyn Williams*, R. Iddenden; Royal
Liverpool University Hospital, C.S. Foster*, P. Cornford.
Memorial Sloan Kettering Cancer Center: P. Scardino*, P Fearn*, V Reuter*, J
Eastham*, M Kattan*, H. Lilja*.
2
Supplementary Table 1 (Adapted from Kristiansena)
Author/Yearb
Bubendorf 1996
Cohort
Type
RP
Cohort Endpoint CutSize
off(%)
137
DFS
7.5
P-Value
Univariate
0.02
P-Value
Multivariate
0.01
2.48
Moul 1996
RP
180
BCR
26
0.001
0.05
3.1
Stattin 1997
WWTURP
125
OS
3
0.00005
0.0023
2.51
Bubendorf 1998
Bxmixed
131
OS
7.5
0.0007
0.0459
Borre 1998
WWTURP
221
OS
10.3
0.0001
0.0002
Khoo 1999
RX
42
BCR
2.4
0.017
NS
Vis 2000
RP
92
Clin
10
0.001
NS
Sebo 2002
RP
454
BCR
0.001
0.008
1.64
Cowen 2002
RX
106
BCR
0.0001
0.003
2.8
Rubin 2002
RP
88
BCR
0.047
0.047
1.49 per 10%
Pollack 2003
RX
106
Met
3.5
0.0005
NS
3.77
Li 2004
RX
108
DM
7.1
0.0003
0.0008
2.39
Pollack 2004
RX
537
BCR
3.5
0.0001
0.04
1.17
Inoue 2005
RP
52
BCR
5
0.0001
0.004
7.517
Rubio 2005
RP
91
BCR
5
0.0014
0.006
3.6
Laitinen 2008
RP
249
BCR
16
0.0001
0.013
1.85
Goto 2008
RP
119
BCR
8.5
0.04
0.96
Gunia 2008
RP
528
BCR
5
0.001
0.048
1.62
Zellweger 2009
BX/RP
279
BCR
10
0.0002
0.05
3.08
Berney 2009
TURPWW
693
OS/DSS
5
0.001
0.0012
1.83
Khor 2009
RX
637
Met
6.3
0.007
1.63
Miyake 2010
RP
193
BCR
5
3.5
0.001
Hazard Ratio
Cont:1.04
0.029
Abbreviations:RP, radical prostatectomy; WW, watchful waiting; TURP, Trans
urethral resection of the prostate; Bx, biopsy; RX, radiotherapy; DFS, disease free
survival; BCR, biochemical recurrence; OS, overall survival; Clin, clinical metastasis;
METS, metastasis;
3
a Kristiansen
G (2012) Diagnostic and prognostic molecular biomarkers for prostate
cancer. Histopathology 60(1):125-41
bAuthor/Year
References:
1. Bubendorf L, Sauter G, Moch H et al. Ki67 labelling index: an independent
predictor of progression in prostate cancer treated by radical prostatectomy. J
Pathol 1996;178;437-441.
2. Moul JW, Bettencourt MC, Sesterhenn IA et al. Protein expression of p53, bcl2, and KI-67 (MIB-1) as prognostic biomarkers in patients with surgically
treated, clinically localized prostate cancer. Surgery 1996;120;159-166;
discussion 166-157.
3. Stattin P, Damber JE, Karlberg L, Bergh A. Cell proliferation assessed by Ki67 immunoreactivity on formalin fixed tissues is a predictive factor for survival
in prostate cancer. J Urol 1997;157;219-222.
4. Bubendorf L, Tapia C, Gasser TC et al. Ki67 labeling index in core needle
biopsies independently predicts tumor-specific survival in prostate cancer.
Hum Pathol 1998;29;949-954
5. Borre M, Bentzen SM, Nerstrom B, Overgaard J. Tumor cell proliferation and
survival in patients with prostate cancer followed expectantly. J Urol
1998;159;1609-1614.
6. Khoo VS, Pollack A, Cowen D et al. Relationship of Ki-67 labeling index to
DNA-ploidy, S-phase fraction, and outcome in prostate cancer treated with
radiotherapy. Prostate 1999;41;166-172.
7. Vis AN, Noordzij MA, Fitoz K, Wildhagen MF, Schroder FH, van der Kwast
TH. Prognostic value of cell cycle proteins p27(kip1) and MIB-1, and the cell
4
adhesion protein CD44s in surgically treated patients with prostate cancer. J
Urol 2000;164;2156-2161.
8. Sebo TJ, Cheville JC, Riehle DL et al. 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 2002;26;431-439.
9. Cowen D, Troncoso P, Khoo VS et al. Ki-67 staining is an independent
correlate of biochemical failure in prostate cancer treated with radiotherapy.
Clin Cancer Res 2002;8;1148-1154.
10. Rubin MA, Dunn R, Strawderman M, Pienta KJ. Tissue microarray sampling
strategy for prostate cancer biomarker analysis. Am J Surg Pathol
2002;26;312-319.
11. Pollack A, Cowen D, Troncoso P et al. Molecular markers of outcome after
radiotherapy in patients with prostate carcinoma: Ki-67, bcl-2, bax, and bcl-x.
Cancer 2003;97;1630-1638.
12. Li R, Heydon K, Hammond ME et al. Ki-67 staining index predicts distant
metastasis and survival in locally advanced prostate cancer treated with
radiotherapy: an analysis of patients in radiation therapy oncology group
protocol 86-10. Clin Cancer Res 2004;10;4118-4124.
13. Pollack A, DeSilvio M, Khor LY 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;22;2133-2140.
5
14. Inoue T, Segawa T, Shiraishi T et al. Androgen receptor, Ki67, and p53
expression in radical prostatectomy specimens predict treatment failure in
Japanese population. Urology 2005;66;332-337.
15. Rubio J, Ramos D, Lopez-Guerrero JA et al. 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
2005;48;745-751.
16. Laitinen S, Martikainen PM, Tolonen T, Isola J, Tammela TL, Visakorpi T.
EZH2, Ki-67 and MCM7 are prognostic markers in prostatectomy treated
patients. Int J Cancer 2008;122;595-602.
17. Goto T, Nguyen BP, Nakano M, Ehara H, Yamamoto N, Deguchi T. 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 2008;72;167-171.
18. Gunia S, Albrecht K, Koch S et al. Ki67 staining index and neuroendocrine
differentiation aggravate adverse prognostic parameters in prostate cancer
and are characterized by negligible inter-observer variability. World J Urol
2008;26;243-250.
19. Zellweger T, Gunther S, Zlobec I et al. 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 2009;124;2116-2123.
20. Berney DM, Gopalan A, Kudahetti S et al. Ki-67 and outcome in clinically
localised prostate cancer: analysis of conservatively treated prostate cancer
6
patients from the Trans-Atlantic Prostate Group study. Br J Cancer
2009;100;888-893.
21. Khor LY, Bae K, Paulus R et al. MDM2 and Ki-67 predict for distant
metastasis and mortality in men treated with radiotherapy and androgen
deprivation for prostate cancer: RTOG 92-02. J Clin Oncol 2009;27;31773184.
22. Miyake H, Muramaki M, Kurahashi T, Takenaka A, Fujisawa M. Expression of
potential molecular markers in prostate cancer: correlation with
clinicopathological outcomes in patients undergoing radical prostatectomy.
Urol Oncol;28;145-151.
7