Utility of Survivin, BAP1, and Ki-67 immunohistochemistry in distinguishing epithelioid mesothelioma from reactive mesothelial hyperplasia

Our plain-English summary of Utility of Survivin, BAP1, and Ki-67 immunohistochemistry in distinguishing epithelioid mesothelioma from reactive mesothelial hyperplasia, by K. Kushitani, V.J. Amatya, A.S. Mawas, et al (Oncology Letters, 2018).

The study

• Authors: K. Kushitani, V.J. Amatya, A.S. Mawas, R. Suzuki, Y. Miyata, M. Okada, K. Inai, T. Kishimoto, Y. Takeshima
• Journal: Oncology Letters
• Published: 2018;15(3):3540-3547
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Histological distinction between epithelioid mesothelioma (EM) and reactive mesothelial hyperplasia (RMH) can be challenging. The aim of this study was to assess the diagnostic utility of Survivin, Ki-67, and loss of BRCA1-associated protein 1 (BAP1) expressions in distinguishing EM from RMH using immunohistochemistry. Formalin-fixed, paraffin-embedded specimens from 78 cases of EM and 80 cases of RMH were immunohistochemically examined for Survivin, BAP1, and Ki-67. In addition, receiver operating characteristic curve analyses were performed to establish the cut-off values for Survivin and Ki-67 labelling indices. Survivin (cut-off value: 5%) had 67.7% sensitivity and 100% specificity, while Ki-67 (cut-off value: 10%) had 85.1% sensitivity and 87.5% specificity, and BAP1 had 66.2% sensitivity and 100% specificity for the differentiation of EM from RMH. Among the combinations of two markers, the combination of Survivin and BAP1 (Survivin-positive and/or BAP1-loss finding) had the highest diagnostic accuracy (sensitivity: 89.8%; specificity: 100%; accuracy: 95.3%). We recommend using the combination of Survivin and BAP1 to distinguish EM from RMH.

In plain English

This Japanese laboratory study tested whether three tissue stains could help tell epithelioid mesothelioma apart from reactive mesothelial hyperplasia. Reactive mesothelial hyperplasia is a non-cancerous condition that can look very similar. The authors stained archived tissue from 78 epithelioid mesothelioma patients and 80 reactive hyperplasia patients for Survivin, Ki-67 and BAP1. Survivin staining above 5% of cells was found in 42 of 62 mesothelioma cases (67.7%) and in none of 70 reactive cases. Ki-67 staining above 10% of cells was found in 57 of 67 mesothelioma cases (85.1%) and in 7 of 56 reactive cases (12.5%). BAP1 loss was seen in 49 of 74 mesothelioma cases (66.2%) and in none of 78 reactive cases. Of the single stains and pairs tested, the most accurate was 'Survivin-positive and/or BAP1-loss', a finding the authors said strongly suggests epithelioid mesothelioma. That combination had a diagnostic accuracy of 95.3%, with sensitivity of 89.8% and specificity of 100%. The authors recommended using Survivin and BAP1 together. The article did not report the patients' asbestos exposure, and not every case had a reported result for every stain.

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 diagnostic-accuracy study of archived tissue samples using immunohistochemistry (tissue staining). Cut-off values were set with receiver operating characteristic (ROC) analysis. Sensitivity, specificity, predictive values and accuracy were then calculated for each stain and for pairs of stains.
• Who was studied: 78 patients with epithelioid mesothelioma, sampled between 2000 and 2016 by thoracoscopic pleural biopsy, pleurectomy/decortication, extrapleural pneumonectomy or autopsy. 80 patients with reactive mesothelial hyperplasia, sampled between 2005 and 2016 by thoracoscopic biopsy, laparoscopic biopsy or surgical resection. All samples came from the archives of the Department of Pathology at Hiroshima University, Japan.
• Exposure: The article did not report asbestos or other exposures for these patients. The study looked at three stains: Survivin (positive above 5% of cells), Ki-67 (positive above 10% of cells) and loss of BAP1.
• Main results:
  • Survivin was positive in 42 of 62 (67.7%) epithelioid mesothelioma cases and in none of the reactive mesothelial hyperplasia cases (0 of 70).
  • Ki-67 was positive in 57 of 67 (85.1%) epithelioid mesothelioma cases and in 7 of 56 (12.5%) reactive mesothelial hyperplasia cases. Ki-67 alone had a sensitivity of 85.1%, a specificity of 87.5% and an accuracy of 86.2%.
  • Loss of nuclear BAP1 was seen in 49 of 74 (66.2%) epithelioid mesothelioma cases. BAP1 was preserved in all 78 reactive mesothelial hyperplasia cases.
  • Among the single stains and pairs of stains, 'Survivin-positive and/or BAP1-loss' had the highest diagnostic accuracy (95.3%), with a sensitivity of 89.8% and a specificity of 100%.
  • The combination of Ki-67 and BAP1 had a diagnostic accuracy of 94.8%.
  • Average Survivin staining was significantly higher in epithelioid mesothelioma (mean 9.3%) than in reactive mesothelial hyperplasia (mean 1.2%). Average Ki-67 staining was also higher in mesothelioma (mean 32.6%) than in reactive hyperplasia (mean 3.5%). Both comparisons had P less than 0.001.
• The authors' conclusion: The authors concluded that a 'Survivin-positive and/or BAP1-loss' finding strongly suggests epithelioid mesothelioma. They recommended using Survivin and BAP1 in combination, and said further evaluation of the Ki-67 labelling index may help.

Topics

Medical terms in this study, explained in our Lexicon: BAP1, Ki-67, Immunohistochemistry, Epithelioid, Mesothelioma, Reactive Mesothelial Hyperplasia.

Related studies

• Diagnostic Utility of BAP1, EZH2 and Survivin in Differentiating Pleural Epithelioid Mesothelioma and Reactive Mesothelial Hyperplasia: Immunohistochemical Study — S.A. Hakim, H.H. Abou Gabal (2021)
• Use of Anti-Noxa Antibody for Differential Diagnosis between Epithelioid Mesothelioma and Reactive Mesothelial Hyperplasia — K. Kushitani, V.J. Amatya, et al. (2016)
• Utility and pitfalls of immunohistochemistry in the differential diagnosis between epithelioid mesothelioma and poorly differentiated lung squamous cell carcinoma — K. Kushitani, V.J. Amatya, et al. (2017)
• MUC4 immunohistochemistry is useful in distinguishing epithelioid mesothelioma from adenocarcinoma and squamous cell carcinoma of the lung — A.S. Mawas, V.J. Amatya, et al. (2018)
• Utility of Methylthioadenosine Phosphorylase Compared With BAP1 Immunohistochemistry, and CDKN2A and NF2 Fluorescence In Situ Hybridization in Separating Reactive Mesothelial Proliferations From Epithelioid Malignant Mesotheliomas — K.B. Berg, S. Dacic, et al. (2018)
• Diagnostic utility of immunohistochemistry in distinguishing between epithelioid pleural mesotheliomas and breast carcinomas: a comparative study — N.G. Ordóñez, A.A. Sahin (2014)

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