Abstract
BackgroundThe 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)).MethodsTo 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.ResultsThe 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).ConclusionThe 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.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6656878501536663Electronic supplementary materialThe online version of this article (doi:10.1186/s13000-015-0294-0) contains supplementary material, which is available to authorized users.
Highlights
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
Was the digital image analysis (DIA) able to reproduce the relationship with clinico-pathological outcomes obtained by visual scoring of Ki-67 index, it had a similar pattern of prediction
The DIA system we used was successfully applied in morphologically complex tumors such as ovarian carcinomas [49], but resulted in high number of manual adjustments for tissue segmentation in our cohort of prostate carcinoma. This result reflects the subtleties in morphologic differences between malignant and benign glands in prostate cancer, as we aimed to perform sharp neoplastic gland segmentation, and the difficulty of DIA modalities to discriminate them without counter verification
Summary
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. Manual counting of a tumor proliferation index is technically long and tedious and subject to intraand inter-observer variability In this context, digital image analysis (DIA) offers a potential adjunct to conventional visual scoring with the promise to increase reproducibility, accuracy and rapidity of the quantification process. Increasing reports of DIA reproducing visual scoring at an acceptable level are found [27, 28] It is unknown whether one method is superior to the other to assess Ki-67 index, even in tumors with a larger hindsight on DIA use such as breast cancer [29]. Such method still needs to be validated against traditional visual assessment for a broader range of patients and tissues
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