Automatic method for assessment of proliferation index in digital images of DLBCL tissue section

Abstract

Abstract Diffuse large B-cell lymphoma (DLBCL) is a fast-growing and aggressive neoplasm originating from B lymphocytes. Evaluation of proliferation index (PI) based on Ki67 immunohistochemical nuclear staining is used to distinguish proliferating (immunopositive) from nonproliferating (immunonegative) lymphoma cells. Human interpretation of PI varies and is time-consuming, therefore automatic computer-assisted approach may facilitate the performance. Herein we propose a new fully automatic proliferation index estimation (FLAPIE) algorithm, dedicated to detection of immunopositive and immunonegative nuclei, and evaluation of PI in digital microscopy images of DAB&H-stained samples from patients with high-grade DLBCL. FLAPIE performs nuclei detection in original RGB colour space and is independent of image brightness due to its textural-statistical approach. Validation of FLAPIE was performed in 61 non-overlapping whole-slide image fragments and compared to the results of PI estimation by QuPath open-source software, MetPiKi algorithm and manual evaluation by two independent observers. Interobserver agreement was calculated between the nuclei count and PIs by two observers. High concordance was found between both DAB and H-stained nuclei count, and PIs by two observers. Compared to MetPiKi, FLAPIE presented improved results of DAB and H-stained nuclei detection. In contrary to MetPiKi and QuPath, FLAPIE performed nuclei detection in all images and its results closely matched the number of DAB-stained nuclei evaluated by two observers. No significant difference was found between PIs by all computational methods and observers. FLAPIE achieved good results in PI estimation and prospectively aims to serve as a tool for clinical application in support of patients selection and decision to treatment.