Low endoglin vascular density and Ki67 index in Gleason score 6 tumours may identify prostate cancer patients suitable for surveillance

Abstract

Objective. The aim of this study was to explore whether vascular density and tumour cell proliferation are related to the risk of prostate cancer death in patients managed by watchful waiting. Material and methods. From a consecutive series of men diagnosed with prostate cancer at transurethral resection in 1975–1990, tissue microarrays (TMAs) were constructed. A majority of men had no metastases at diagnosis and were followed by watchful waiting (n = 295). The TMAs were stained for Ki67, endoglin and factor VIII-related antigen (vWf). Results. In univariate Cox analyses, increased Ki67 index, endoglin vascular density and vWf vascular density were associated with shorter cancer-specific survival. Ki67 index and endoglin vascular density added independent prognostic information to clinical stage, estimated tumour size and Gleason score (GS) in multivariate Cox analysis. In GS 6 tumours, high Ki67 index and high endoglin vascular density identified patients with poor outcome. After 15 years of follow-up not a single man out of 34 men with low staining for both markers (35% of all GS 6 tumours) had died of prostate cancer, in contrast to 15 prostate cancer deaths among the remaining 63 men with GS 6 tumours (65% cumulative risk of prostate cancer death). vWf vascular density in benign areas was a prognostic marker in GS 6 and 7 tumours. Conclusions. Men with GS 6 tumours with both low Ki67 index and endoglin vascular density staining scores have a low risk of progression. Additional studies are needed to test whether these two markers can be applied to core biopsies to select patients suitable for surveillance.

Key Words::

• endoglin
• Ki67
• prostate cancer
• prognostic markers
• TINT
• vWf

Acknowledgements

This work was supported by grants from the Swedish Cancer Society (project 4716), the Swedish Research Council, the Umeå University Hospital, the Lions Cancer Research Foundation and Umeå University. The authors thank Mrs Birgitta Ekblom, Mrs Elisabeth Dahlberg and Mrs Pernilla Andersson for skilful technical assistance with immunostaining, and Erik Holmberg for statistical assistance.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.