Automated assessment of Ki‐67 in breast cancer: the utility of digital image analysis using virtual triple staining and whole slide imaging

• Published in: Histopathology 2020-09, Vol.77 (3), p.471-480
• Main Authors: Hida, Akira I, Omanovic, Dzenita, Pedersen, Lars, Oshiro, Yumi, Ogura, Takashi, Nomura, Tsunehisa, Kurebayashi, Junichi, Kanomata, Naoki, Moriya, Takuya
• Format: Article
• Language: English
• Subjects: automated pathology; Automation; Breast cancer; Cytokeratin; digital image analysis; Image processing; Invasiveness; Ki‐67; luminal‐type breast cancer; Medical prognosis; Patients; standardisation; Surgery; virtual triple staining
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/his.14140

Aims Precise evaluation of proliferative activity is essential for the stratified treatment of luminal‐type breast cancer (BC). Immunohistochemical staining of Ki‐67 has been widely used to determine proliferative activity and is recognised to be a useful prognostic marker. However, there remains discussion concerning the methodology. We aimed to develop an automated and reliable Ki‐67 assessment approach for invasive BC. Materials and results A retrospective study was designed to include two cohorts consisting of 152 and 261 consecutive patients with luminal‐type BC. Representative tissue blocks following surgery were collected, and three serial sections were stained automatically with Ki‐67, pan‐cytokeratin and p63. The whole slides were scanned digitally and aligned using VirtualTripleStaining – an extension to the VirtualDoubleStaining™ technique provided by Visiopharm software. The aligned files underwent automated invasive cancer detection, hot‐spot identification and Ki‐67 counting. The automated scores showed a significant positive correlation with the pathologists' scores (r = 0.82, P