Prognostic value of Ki67 in localized prostate carcinoma: a multi-institutional study of >1000 prostatectomies

Abstract

Background Expanding interest in and use of active surveillance for early state prostate cancer has increased need for prognostic biomarkers. Using a multi-institutional tissue microarray resource including over 1000 radical prostatectomy samples, we sought to correlate Ki67 expression captured by an automated image analysis system with clinico-pathologic features and validate its utility as a clinical grade test in predicting cancer-specific outcomes. Methods After immunostaining, the Ki67 proliferation index (PI) of tumor areas of each core (3 cancer cores/case) was analyzed using a nuclear quantification algorithm (Aperio). We assessed whether Ki67 PI was associated with clinico-pathologic factors and recurrence free survival including biochemical recurrence, metastasis or PC death (7-year median follow-up). Results In 1004 PCs (~4,000 tissue cores) Ki67 PI showed significantly higher inter-tumor (0.68) than intra-tumor variation (0.39). Ki67 PI was associated with stage (p<0.0001), seminal vesicle invasion (SVI, p=0.02), extracapsular extension (ECE, p<0.0001) and Gleason Score (GS, p<0.0001). Ki67 PI as a continuous variable significantly correlated with recurrence free, overall and disease-specific survival by multivariable Cox proportional hazard model (HR=1.04–1.1, p=0.02–0.0008). High Ki67 score (defined as ≥5%) was significantly associated with worse recurrence free survival (HR=1.47, p=0.0007) and worse overall survival (HR=2.03, p=0.03). Conclusion In localized PC treated by radical prostatectomy, higher Ki67 PI assessed using a clinical grade automated algorithm is strongly associated with a higher GS, stage, SVI and ECE, and greater probability of recurrence.

High cyclin A expression, but not Ki67, is associated with early recurrence in desmoid tumors

“…High Ki67 and cyclin A are associated with a poor prognosis in breast cancer, prostate carcinomas, and soft‐tissue sarcomas . However, the role of proliferation in desmoid tumors has not been clearly defined.…”

“…9 High Ki67 and cyclin A are associated with a poor prognosis in breast cancer, prostate carcinomas, and soft-tissue sarcomas. [10][11][12] However, the role of proliferation in desmoid tumors has not been clearly defined. Ki67 expression in desmoid tumors has been assessed using various techniques and cut-off points, with inconsistent results.…”

An analysis of a multiple biomarker panel to better predict prostate cancer metastasis after radical prostatectomy

“…Indeed, AZGP1 and Ki67 have been extensively studied and shown to be successful as individual markers of PCa recurrence. Ki67 is arguably one of the most studied individual IHC markers in PCa; In a multi‐institutional study of over 1,000 cases, higher Ki67 was strongly associated with a greater probability of recurrence‐free and overall survival . Ki67 assessed on prostate needle biopsies has also been demonstrated as a useful individual marker in predicting PCa death .…”

“…Ki67 is arguably one of the most studied individual IHC markers in PCa; In a multi-institutional study of over 1,000 cases, higher Ki67 was strongly associated with a greater probability of recurrence-free and overall survival. 33 Ki67 assessed on prostate needle biopsies has also been demonstrated as a useful individual marker in predicting PCa death. 34 The utility of AZGP1 as an individual biomarker in PCa is also supported by a significant number of single-center studies demonstrating its role in predicting PSA recurrence.…”

DNA Damage Induces a Secretory Program in the Quiescent TME that Fosters Adverse Cancer Phenotypes

“…Prostate tissue staining for Ki-67/MIB-1 has been described previously (25). The monoclonal antibody, MIB-1 (clone MIB-1, DAKO) was used to determine the proportion of cancer epithelial, cancer-associated stromal and benign-associated stromal cells staining positive for Ki-67.…”