Automated assessment of Ki-67 proliferation index in neuroendocrine tumors by deep learning

APMIS. 2022 Jan;130(1):11-20. doi: 10.1111/apm.13190. Epub 2021 Nov 22.

Abstract

The Ki-67 proliferation index (PI) is a prognostic factor in neuroendocrine tumors (NETs) and defines tumor grade. Analysis of Ki-67 PI requires calculation of Ki-67-positive and Ki-67-negative tumor cells, which is highly subjective. To overcome this, we developed a deep learning-based Ki-67 PI algorithm (KAI) that objectively calculates Ki-67 PI. Our study material consisted of NETs divided into training (n = 39), testing (n = 124), and validation (n = 60) series. All slides were digitized and processed in the Aiforia® Create (Aiforia Technologies, Helsinki, Finland) platform. The ICC between the pathologists and the KAI was 0.89. In 46% of the tumors, the Ki-67 PIs calculated by the pathologists and the KAI were the same. In 12% of the tumors, the Ki-67 PI calculated by the KAI was 1% lower and in 42% of the tumors on average 3% higher. The DL-based Ki-67 PI algorithm yields results similar to human observers. While the algorithm cannot replace the pathologist, it can assist in the laborious Ki-67 PI assessment of NETs. In the future, this approach could be useful in, for example, multi-center clinical trials where objective estimation of Ki-67 PI is crucial.

Keywords: Ki-67 proliferation index; deep learning; digital pathology; neuroendocrine neoplasm.

MeSH terms

  • Algorithms
  • Automation
  • Biomarkers, Tumor*
  • Cell Proliferation
  • Deep Learning
  • Diagnostic Tests, Routine / methods
  • Finland
  • Humans
  • Image Processing, Computer-Assisted / methods*
  • Ki-67 Antigen / metabolism*
  • Neuroendocrine Tumors / classification
  • Neuroendocrine Tumors / diagnosis*
  • Neuroendocrine Tumors / metabolism*
  • Pathology, Clinical / methods*
  • Reproducibility of Results

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen