Combination of CK20 and Ki-67 immunostaining analysis predicts recurrence, progression, and cancer-specific survival in pT1 urothelial bladder cancer.
BACKGROUND
The prognostic value of CK20, Ki-67, and p53 has been investigated for non-muscle-invasive urothelial bladder cancers but not for the distinct and clinically challenging subset of pT1 bladder cancers.


OBJECTIVE
To evaluate the prognostic value of CK20, Ki-67, and p53 within the largest series of pT1 urothelial bladder cancers.


METHODS
Data from 309 patients with pT1 urothelial bladder cancer from one single urologic centre were collected.


METHODS
Adjuvant instillation of bacillus Calmette-Guérin was performed in each patient. A second resection was performed after 4-8 wk. A total of 76 patients underwent cystectomy.


METHODS
We conducted histomorphologic analysis; immunohistochemistry for CK20, Ki-67, and p53; and univariate and multivariate Cox regression models including recurrence-free survival (RFS), progression-free survival (PFS), and cancer-specific survival (CSS).


CONCLUSIONS
At a median follow-up of 49 mo, we found recurrence and progression and disease-specific mortality rates of 22.7%, 20.1%, and 15.9%, respectively. CK20 expression was significantly correlated with RFS in multivariate analysis (hazard ratio [HR]: 5.89; 95% confidence interval [CI], 1.44-24.15; p=0.014). In multivariate analysis, Ki-67 was the only marker significantly correlated with PFS (HR: 2.80; 95% CI, 1.45-5.43, p=0.002). Ki-67 (HR: 3.83; 95% CI, 1.59-9.26; p=0.003), and CK20 (HR: 8.44; 95% CI,1.16-61.34; p=0.035) were significantly correlated with CSS in multivariate analysis. The combination of CK20 and Ki-67 showed significantly worse RFS (p=0.026), PFS (p=0.003), and CSS (p<0.001) in tumours with a high proliferation index and abnormal CK20 expression. A retrospective study design was the major limitation of this study.


CONCLUSIONS
Our present analysis of the largest series of patients with pT1 urothelial bladder cancer published to date found Ki-67 and CK20 to be potential prognostic markers improving the risk stratification of pT1 bladder tumours. They are reliable indicators of biologic aggressiveness and may contribute to decision making on therapeutic strategy for pT1 bladder carcinomas.
Department of Pathology, University of Erlangen-Nuremberg, Erlangen, Germany. Electronic address: simone.bertz@uk-erlangen.de.
Simone
S
Bertz
Wolfgang
W
Otto
Stefan
S
Denzinger
Wolf F
WF
Wieland
Maximilian
M
Burger
Robert
R
Stöhr
Stefan
S
Link
Ferdinand
F
Hofstädter
Arndt
A
Hartmann
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000737:chemistry* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053554:Keratin-20 / Q000032:analysis* / Q000096:biosynthesis; D019394:Ki-67 Antigen / Q000032:analysis* / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality*; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology
D053554:Keratin-20; D019394:Ki-67 Antigen