Comparison of digital image analysis and visual scoring of KI-67 in prostate cancer prognosis after prostatectomy

OBJECTIVE - The tumor proliferative index marker Ki-67 was shown to be associated with clinically significant outcomes in prostate cancer, but its clinical application has limitations due to lack of uniformity and consistency in quantification. Our objective was to compare the measurements obtained with digital image analysis (DIA) versus virtual microscopy (visual scoring (VS)).

METHODS - To do so, we compared the measurement distributions of each technique and their ability to predict clinically useful endpoints. A tissue microarray series from a cohort of 225 men who underwent radical prostatectomy was immunostained for Ki-67. The percentage of Ki-67 positive nuclei in malignant cells was assessed both by VS and DIA, and a H-score was calculated. The distribution and predictive ability of these scoring methods to predict biochemical recurrence (BCR) and death from prostate cancer (DPCa) were compared using Mann-Whitney test and C-index.

RESULTS - The measurements obtained with VS were similar to the DIA measurements (p = 0.73) but dissimilar to the H-score (p < 0.001). Cox regression models showed that Ki-67 was associated with BCR (HR 1.46, 95 % CI 1.10-1.94) and DPCa (HR 1.26, 95 % CI 1.06-1.50). C-indexes revealed that Ki-67 was a better predictor of DPCa (0.803, 0.8059 and 0.789; VS, DIA and H-score, respectively) than of BCR (0.625, 0.632 and 0.604; VS, DIA and H-score, respectively).

CONCLUSIONS - The measurement distributions and the predictive abilities of VS and DIA were similar and presented the same predictive behaviour in our cohort, supporting the role of Ki-67 proliferative index as an important prognostic factor of BCR and DPCa in prostate cancer post RP.

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6656878501536663.

Diagn Pathol. 2015 Jun 13;10:67. doi: 10.1186/s13000-015-0294-0.

Desmeules P1,2, Hovington H3,4, Nguilé-Makao M5,6, Léger C7,8, Caron A9,10, Lacombe L11,12, Fradet Y13,14, Têtu B15,16, Fradet V17,18,19.

1 Cancer Research Centre, CHU de Québec, Québec, Canada. .
2 Anatomic Pathology and Cytology Department, Hôpital du St-Sacrement, Centre Hospitalier Universitaire (CHU) de Québec, Laval University, Québec, Canada.
3 Department of Surgery/Urology, Faculty of Medicine, Laval University, Québec, Canada.
4 Cancer Research Centre, CHU de Québec, Québec, Canada. Helene. 5 Department of Surgery/Urology, Faculty of Medicine, Laval University, Québec, Canada.
6 Cancer Research Centre, CHU de Québec, Québec, Canada.
7 Department of Surgery/Urology, Faculty of Medicine, Laval University, Québec, Canada.
8 Cancer Research Centre, CHU de Québec, Québec, Canada. 9 Department of Medicine, Faculty of Medicine, University of Montreal, Montreal, Canada.
10 Population Health Unit (URESP), Centre de recherche FRQS du Centre hospitalier affilié universitaire de Québec, Québec, Canada. .
11 Department of Surgery/Urology, Faculty of Medicine, Laval University, Québec, Canada.
12 Cancer Research Centre, CHU de Québec, Québec, Canada.
13 Department of Surgery/Urology, Faculty of Medicine, Laval University, Québec, Canada.
14 Cancer Research Centre, CHU de Québec, Québec, Canada.
15 Cancer Research Centre, CHU de Québec, Québec, Canada.
16 Anatomic Pathology and Cytology Department, Hôpital du St-Sacrement, Centre Hospitalier Universitaire (CHU) de Québec, Laval University, Québec, Canada. Bernard.
17 Department of Surgery/Urology, Faculty of Medicine, Laval University, Québec, Canada.
18 Cancer Research Centre, CHU de Québec, Québec, Canada. .
19 Centre de recherche en cancérologie de l'Université Laval, Centre Hospitalier Universitaire de Québec - pavillon L'Hôtel-Dieu de Québec, 10 rue McMahon, Québec, QC, G1R3S1, Canada.