Ki-67 is an independent predictor of prostate cancer death in routine needle biopsy samples: proving utility for routine assessments

Solène-Florence Kammerer-Jacquet (1, 2, 3) , Amar Ahmad (3) , Henrik Moller (4) , Holly Sandu (3) , Peter Scardino (5) , Geraldine Soosay , Luis Beltran (3) , Jack Cuzick (3) , Daniel Berney (3)

1 Service de Pathologie [Rennes] = Pathology [Rennes]
2 Irset - Institut de recherche en santé, environnement et travail
3 QMUL - Queen Mary University of London
4 King‘s College London
5 Memorial Sloane Kettering Cancer Center [New York]

Standard clinical parameters fail to accurately differentiate indolent from aggressive prostate cancer. Our previous studies showed that immunohistochemical testing for Ki-67 improved prediction of prostate cancer death in a previous cohort of conservatively treated clinically localized prostate cancer. However there is a need for validation of usage with whole biopsy sections rather than tissue micro-arrays for use in routine diagnostics. Prostate cancer biopsy cases were identified in the UK, between 1990 and 2003, treated conservatively. Tumor extent and prostate-specific antigen (PSA) serum measurements were available. Biopsy cases were centrally reviewed by three uropathologists and Gleason conformed to contemporary ISUP 2014 criteria. Follow-up was through cancer registries up until 2012. Deaths were divided into those from prostate cancer and those from other causes. The percentage of Ki-67 in tumor cells was evaluated by immunohistochemistry on whole biopsy sections and was available for 756 patients. This percentage was used in analysis of cancer specific survival using a Cox proportional hazards model. In univariate analysis, the interquartile hazard ratio (HR) (95% confidence intervals) for continuous Ki-67 was 1.68 (1.49, 1.89), χ 1 2 = 47.975, P < 0.001. In grade groups 1 and 2, continuous Ki-67 was a statistically significant predictor of time to death from prostate cancer, HR (95% CI) = 1.97 (1.34, 2.88), χ 1 2 = 9.017, p = 0.003. In multivariate analysis, continuous Ki-67 added significant predictive information to that provided by grade groups, extent of disease and serum PSA, HR (95% CI) = 1.34 (1.16, 1.54), Δχ 1 2 = 13.703, P < 0.001. We now advocate the introduction of Ki-67 as a viable and practicable prognostic biomarker in clinical practice. The association of Ki-67 with mortality was highest in grade groups 1 and 2, showing that Ki-67 can be used as a routine biomarker in patients being considered for active surveillance.

Domaines: Cancer; Urologie et Néphrologie

Solène-Florence Kammerer-Jacquet, Amar Ahmad, Henrik Moller, Holly Sandu, Peter Scardino, et al.. Ki-67 is an independent predictor of prostate cancer death in routine needle biopsy samples: proving utility for routine assessments. Modern Pathology, 2019, 32 (9), pp.1303-1309. ⟨10.1038/s41379-019-0268-y⟩. ⟨hal-02473289⟩