Mitotic and Proliferative Indices in WHO Grade III Meningioma

Meningiomas with inherently high mitotic indices and poor prognosis, such as WHO grade III meningiomas, have not been investigated separately to establish interchangeability between conventional mitotic index counted on H&E stained slides (MI) and mitotic index counted on phosphohistone-H3 stain...

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Main Authors: Andrea Daniela Maier, Christian Beltoft Brøchner, Jiri Bartek Jr., Frank Eriksson, Heidi Ugleholdt, Helle Broholm, Tiit Mathiesen
Format: Article
Language:English
Published: MDPI AG 2020-11-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/12/11/3351
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author Andrea Daniela Maier
Christian Beltoft Brøchner
Jiri Bartek Jr.
Frank Eriksson
Heidi Ugleholdt
Helle Broholm
Tiit Mathiesen
author_facet Andrea Daniela Maier
Christian Beltoft Brøchner
Jiri Bartek Jr.
Frank Eriksson
Heidi Ugleholdt
Helle Broholm
Tiit Mathiesen
author_sort Andrea Daniela Maier
collection DOAJ
description Meningiomas with inherently high mitotic indices and poor prognosis, such as WHO grade III meningiomas, have not been investigated separately to establish interchangeability between conventional mitotic index counted on H&E stained slides (MI) and mitotic index counted on phosphohistone-H3 stained slides (PHH3 MI). This study investigates the agreement of MI and PHH3 MI and to analyze the association of progression-free survival (PFS) and MI, PHH3 MI, and the proliferative index (PI, Ki-67) in WHO grade III meningioma. Tumor specimens from 24 consecutive patients were analyzed for expression of Ki-67, PHH3 MI, and MI. Quantification was performed independently by two observers who made replicate counts in hot spots and overall tumor staining. Repeatability in replicate counts from MI and PHH3 MI was low in both observers. Consequently, we could not report the agreement. MI, PHH3 MI and hot spot counts of Ki-67 were associated with PFS (MI hot spot HR = 1.61, 95% CI 1.12–2.31, <i>p</i> = 0.010; PHH3 MI hot spot HR = 1.59, 95% CI 1.15–2.21, <i>p</i> = 0.006; Ki-67 hot spot HR = 1.06, 95% CI 1.02–1.11. <i>p</i> = 0.004). We found markedly low repeatability of manually counted MI and PHH3 MI in WHO grade III meningioma, and we could not conclude that the two methods agreed. Subsequently, quantification with better repeatability should be sought. All three biomarkers were associated with PFS.
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spelling doaj.art-c72994f972624fca95f0d19e9c96bea32023-11-20T20:43:58ZengMDPI AGCancers2072-66942020-11-011211335110.3390/cancers12113351Mitotic and Proliferative Indices in WHO Grade III MeningiomaAndrea Daniela Maier0Christian Beltoft Brøchner1Jiri Bartek Jr.2Frank Eriksson3Heidi Ugleholdt4Helle Broholm5Tiit Mathiesen6Department of Neurosurgery, Copenhagen University Hospital, Rigshospitalet, Inge Lehmanns Vej 6, 2100 Copenhagen, DenmarkPathology Department, Copenhagen University Hospital, Rigshospitalet, Inge Lehmanns Vej 7, 2100 Copenhagen, DenmarkDepartment of Neurosurgery, Copenhagen University Hospital, Rigshospitalet, Inge Lehmanns Vej 6, 2100 Copenhagen, DenmarkSection of Biostatistics, Department of Public Health, University of Copenhagen, Øster Farimagsgade 5, 1014 Copenhagen, DenmarkPathology Department, Copenhagen University Hospital, Rigshospitalet, Inge Lehmanns Vej 7, 2100 Copenhagen, DenmarkPathology Department, Copenhagen University Hospital, Rigshospitalet, Inge Lehmanns Vej 7, 2100 Copenhagen, DenmarkDepartment of Neurosurgery, Copenhagen University Hospital, Rigshospitalet, Inge Lehmanns Vej 6, 2100 Copenhagen, DenmarkMeningiomas with inherently high mitotic indices and poor prognosis, such as WHO grade III meningiomas, have not been investigated separately to establish interchangeability between conventional mitotic index counted on H&E stained slides (MI) and mitotic index counted on phosphohistone-H3 stained slides (PHH3 MI). This study investigates the agreement of MI and PHH3 MI and to analyze the association of progression-free survival (PFS) and MI, PHH3 MI, and the proliferative index (PI, Ki-67) in WHO grade III meningioma. Tumor specimens from 24 consecutive patients were analyzed for expression of Ki-67, PHH3 MI, and MI. Quantification was performed independently by two observers who made replicate counts in hot spots and overall tumor staining. Repeatability in replicate counts from MI and PHH3 MI was low in both observers. Consequently, we could not report the agreement. MI, PHH3 MI and hot spot counts of Ki-67 were associated with PFS (MI hot spot HR = 1.61, 95% CI 1.12–2.31, <i>p</i> = 0.010; PHH3 MI hot spot HR = 1.59, 95% CI 1.15–2.21, <i>p</i> = 0.006; Ki-67 hot spot HR = 1.06, 95% CI 1.02–1.11. <i>p</i> = 0.004). We found markedly low repeatability of manually counted MI and PHH3 MI in WHO grade III meningioma, and we could not conclude that the two methods agreed. Subsequently, quantification with better repeatability should be sought. All three biomarkers were associated with PFS.https://www.mdpi.com/2072-6694/12/11/3351malignant meningiomamitotic indiceshot spotsKi-67agreement
spellingShingle Andrea Daniela Maier
Christian Beltoft Brøchner
Jiri Bartek Jr.
Frank Eriksson
Heidi Ugleholdt
Helle Broholm
Tiit Mathiesen
Mitotic and Proliferative Indices in WHO Grade III Meningioma
Cancers
malignant meningioma
mitotic indices
hot spots
Ki-67
agreement
title Mitotic and Proliferative Indices in WHO Grade III Meningioma
title_full Mitotic and Proliferative Indices in WHO Grade III Meningioma
title_fullStr Mitotic and Proliferative Indices in WHO Grade III Meningioma
title_full_unstemmed Mitotic and Proliferative Indices in WHO Grade III Meningioma
title_short Mitotic and Proliferative Indices in WHO Grade III Meningioma
title_sort mitotic and proliferative indices in who grade iii meningioma
topic malignant meningioma
mitotic indices
hot spots
Ki-67
agreement
url https://www.mdpi.com/2072-6694/12/11/3351
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