Ki67 proliferation index in medullary thyroid carcinoma: A comparative study of multiple counting methods and validation of image analysis and deep learning platforms Journal Article


Authors: Nadeem, S.; Hanna, M. G.; Viswanathan, K.; Marino, J.; Ahadi, M.; Alzumaili, B.; Bani, M. A.; Chiarucci, F.; Chou, A.; De Leo, A.; Fuchs, T. L.; Lubin, D. J.; Luxford, C.; Magliocca, K.; Martinez, G.; Shi, Q.; Sidhu, S.; Al Ghuzlan, A.; Gill, A. J.; Tallini, G.; Ghossein, R.; Xu, B.
Article Title: Ki67 proliferation index in medullary thyroid carcinoma: A comparative study of multiple counting methods and validation of image analysis and deep learning platforms
Abstract: Aims: The International Medullary Thyroid Carcinoma Grading System, introduced in 2022, mandates evaluation of the Ki67 proliferation index to assign a histological grade for medullary thyroid carcinoma. However, manual counting remains a tedious and time-consuming task. Methods and results: We aimed to evaluate the performance of three other counting techniques for the Ki67 index, eyeballing by a trained experienced investigator, a machine learning-based deep learning algorithm (DeepLIIF) and an image analysis software with internal thresholding compared to the gold standard manual counting in a large cohort of 260 primarily resected medullary thyroid carcinoma. The Ki67 proliferation index generated by all three methods correlate near-perfectly with the manual Ki67 index, with kappa values ranging from 0.884 to 0.979 and interclass correlation coefficients ranging from 0.969 to 0.983. Discrepant Ki67 results were only observed in cases with borderline manual Ki67 readings, ranging from 3 to 7%. Medullary thyroid carcinomas with a high Ki67 index (≥ 5%) determined using any of the four methods were associated with significantly decreased disease-specific survival and distant metastasis-free survival. Conclusions: We herein validate a machine learning-based deep-learning platform and an image analysis software with internal thresholding to generate accurate automatic Ki67 proliferation indices in medullary thyroid carcinoma. Manual Ki67 count remains useful when facing a tumour with a borderline Ki67 proliferation index of 3–7%. In daily practice, validation of alternative evaluation methods for the Ki67 index in MTC is required prior to implementation. © 2023 John Wiley & Sons Ltd.
Keywords: cancer survival; controlled study; major clinical study; ki 67 antigen; cell proliferation; ki-67 antigen; image analysis; cohort analysis; retrospective study; intermethod comparison; thyroid neoplasms; grade; thyroid tumor; disease specific survival; thyroid medullary carcinoma; machine learning; learning algorithm; proliferation index; distant metastasis free survival; medullary thyroid carcinoma; humans; human; article; deep learning; ki67 proliferation index; thyroid cancer, medullary
Journal Title: Histopathology
Volume: 83
Issue: 6
ISSN: 0309-0167
Publisher: Wiley Blackwell  
Date Published: 2023-12-01
Start Page: 981
End Page: 988
Language: English
DOI: 10.1111/his.15048
PUBMED: 37706239
PROVIDER: scopus
PMCID: PMC10840805
DOI/URL:
Notes: Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed -- MSK corresponding author is Bin Xu -- Source: Scopus
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MSK Authors
  1. Ronald A Ghossein
    482 Ghossein
  2. Bin   Xu
    227 Xu
  3. Matthew George Hanna
    101 Hanna
  4. Saad Nadeem
    50 Nadeem
  5. Joseph Marino
    5 Marino