Ki-67 Proliferation Index Is Associated With Tumor Grade and Survival in Pleural Epithelioid Mesotheliomas

Our plain-English summary of Ki-67 Proliferation Index Is Associated With Tumor Grade and Survival in Pleural Epithelioid Mesotheliomas, by B. Galeano, C.J. Smith, E.S. Yi, et al (The American Journal of Surgical Pathology, 2024).

The study

• Authors: B. Galeano, C.J. Smith, E.S. Yi, A.C. Roden, S. Jenkins, J. Capelle, M. Kittle-Francis, A.S. Mansfield, M.C. Aubry
• Journal: The American Journal of Surgical Pathology
• Published: 2024;48(5):615-622
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pleural epithelioid mesothelioma (PEM) is divided into low and high grades based on nuclear atypia, mitoses, and necrosis in the tumor. Assessing mitoses and nuclear atypia tend to be labor-intensive with limited reproducibility. Ki-67 proliferation index was shown to be a prognostic factor in PEM, but its performance has not been directly correlated with tumor grade or mitotic score. This study evaluated the potential of Ki-67 index as a surrogate of tumor grade. We also compared the predictability of mitoses and Ki-67 index for overall survival (OS). Ninety-six PEM samples from 85 patients were identified from the surgical pathology file during 2000-2021 at our institution, and all glass slides were reviewed by 2 pulmonary pathologists to confirm the diagnosis and assign the tumor grade. Digital image analysis (DIA) was done for Ki-67 index. The agreement on tumor grading between 2 reviewers was moderate (kappa value = 0.47). The correlation between mitotic count (average count by 2 reviewers) and Ki-67 index was 0.65. The areas under the curve for predicting tumor grade by mitotic score and Ki-67 index were 0.84 and 0.74 (reviewer 1) and 0.85 and 0.81 (reviewer 2), respectively. High Ki-67 index and mitoses were significantly associated with poor OS ( P =0.03 and 0.0005, using 30% and 10/2 mm 2 as cutoffs, respectively). In conclusion, Ki-67 index by DIA was associated with tumor grade as well as mitotic count, and its predictability for OS was comparable to that of mitotic score, thus being a potential surrogate for tumor grade.

Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.

In plain English

This study at Mayo Clinic tested whether a lab test could stand in for the tumor grade used to classify pleural epithelioid mesothelioma. The test, the Ki-67 index, is the percentage of tumor cells staining positive for a proliferation marker, read by computer image analysis. The authors reviewed 96 tissue samples from 85 patients collected from 2000 to 2021. Two pathologists separately graded each sample as low or high grade under the 2021 WHO system, and their agreement was moderate (kappa 0.47). Ki-67 was higher in high-grade tumors (median 29.5 vs 13.5 for reviewer 1; 31.4 vs 13.7 for reviewer 2). Patients with Ki-67 of 30% or more had worse overall survival than those below 30% (hazard ratio 1.79, 95% CI 1.06 to 2.96, P = 0.03). Patients with 10 or more mitoses per 2 square millimeters (reviewers' average) had worse survival than those with fewer (hazard ratio 3.21, 95% CI 1.72 to 5.72, P = 0.0005). The authors concluded Ki-67 could be considered a viable surrogate for tumor grade, noting relatively low case numbers. The study did not examine asbestos exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective single-institution pathology review. Two pathologists graded the slides, Ki-67 was measured by digital image analysis, and survival was analyzed.
• Who was studied: 96 tissue specimens from 85 patients with pleural epithelioid mesothelioma, from biopsies or surgical resections at Mayo Clinic, Rochester, MN, 2000 to 2021. Mean age at diagnosis was 67.2 years.
• Exposure: No asbestos or other exposure was studied. The study measured tumor features: the Ki-67 proliferation index, mitotic count, nuclear atypia, necrosis, and WHO tumor grade.
• Main results:
  • The two reviewers showed moderate agreement on overall WHO tumor grade (kappa 0.47) and only fair agreement on nuclear atypia (kappa 0.37).
  • Ki-67 index was significantly higher in high-grade than in low-grade tumors: median 29.5 vs. 13.5 (reviewer 1) and 31.4 vs. 13.7 (reviewer 2).
  • The correlation between mitotic count (averaged across reviewers) and Ki-67 index was 0.65. Areas under the curve for predicting tumor grade were 0.84 for mitotic count and 0.74 for Ki-67 (reviewer 1), and 0.85 and 0.81 (reviewer 2).
  • Patients with a Ki-67 index of 30% or more had worse overall survival than those below 30%: hazard ratio 1.79 (95% CI 1.06 to 2.96), 1-year survival 60.0% vs. 76.2%, P = 0.03.
  • Patients with reviewer-averaged mitotic counts of 10 or more per 2 mm2 had worse overall survival than those with fewer than 10: hazard ratio 3.21 (95% CI 1.72 to 5.72), 1-year survival 43.8% vs. 78.0%, P = 0.0005.
  • WHO tumor grade (high vs. low) gave hazard ratios for death of 1.27 (95% CI 0.80 to 2.03) for reviewer 1 and 1.55 (95% CI 0.95 to 2.49) for reviewer 2.
  • Among the 85 patients, median survival from diagnosis was 1.5 years (95% CI 1.2 to 1.6 years).
  • Ki-67 index predicted survival about as well as mitotic count (C-index 0.56 vs. 0.59).
• The authors' conclusion: The authors concluded that Ki-67 index by digital image analysis can be considered a viable surrogate of tumor grade. They also suggested that the WHO mitotic score categories may be reconsidered.
• Limitations the authors state:
  • The number of cases was relatively low.
  • For the 11 patients with 2 procedures, findings differed between specimens. Because the cases were few and the time between procedures varied widely, the causes could not be determined.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Ki-67, Epithelioid, Mesothelioma, Nuclear Atypia, Necrosis, Overall Survival, Pathology, Mitotic Count.

Related studies

• Ki67 proliferation index augments two-tier tumour grade in prediction of survival and progression-free survival in epithelioid pleural mesothelioma — G.A. Lynch, Y.Z. Zhang, et al. (2026)
• Comparison of SKIP expression in malignant pleural mesotheliomas with Ki-67 proliferation index and prognostic parameters — G. Türkcü, U. AlabalIk, et al. (2016)
• Combined grade and nuclear grade are prognosis predictors of epithelioid malignant peritoneal mesothelioma: a multi-institutional retrospective study — N. Benzerdjeb, P. Dartigues, et al. (2021)
• Prognostic significance of morphological growth patterns and mitotic index of epithelioid malignant peritoneal mesothelioma — A.M. Krasinskas, A.C. Borczuk, et al. (2016)
• Nuclear grade and necrosis predict prognosis in malignant epithelioid pleural mesothelioma: a multi-institutional study — L.E. Rosen, T. Karrison, et al. (2018)
• Presence of pleomorphic features but not growth patterns improves prognostic stratification of epithelioid malignant pleural mesothelioma by 2-tier nuclear grade — Y.Z. Zhang, C. Brambilla, et al. (2020)

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