2021•ApmisOpen access

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

Tiina Vesterinen, Jenni Säilä, Sami Blom, Mirkka Pennanen, Helena Leijon, Johanna Arola

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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.

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What this paper is about

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.

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Available 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.

Key concepts: Ki-67, Proliferation index, Neuroendocrine tumors, Pi, Proliferative index, Medicine, Algorithm, Pathology

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