Double Staining Immunohistochemistry and Digital Pathology: Moving Towards Standardization of the Proliferative Index Evaluation in Meningiomas

TL;DR

This study shows that double staining and digital pathology can improve the accuracy of evaluating the proliferation index in meningiomas, helping standardize tumor grading.

Contribution

The study introduces a standardized method using double staining immunohistochemistry and digital pathology for meningioma proliferation index evaluation.

Findings

Ki-67 expression varied by meningioma grade, with digital image analysis showing high agreement with manual assessments.

Double staining immunohistochemistry improved accuracy in evaluating diagnostic and proliferative markers in tumor samples.

Abstract

Background: Although Ki-67 is not included among the grading criteria in the current WHO Classification of Tumours of the Central Nervous System (CNS), it provides valuable, albeit limited, prognostic information. Immunohistochemistry for Ki-67 can reveal uneven proliferation patterns and assist in the assessment of mitotic counts. Several studies indicate that meningiomas with a proliferation index > 4% show recurrence rates comparable to CNS WHO grade 2 (atypical) tumors, while tumors with an index > 20% are associated with mortality rates similar to CNS WHO grade 3 (anaplastic) meningiomas. Issues related to Ki-67 assessment include interobserver variability, the use of different cut-off values among pathologists, and the presence of a complex inflammatory tumour microenvironment, which may lead to an overestimation of the proliferative index (PI). Methods: In this study, we describe how Double Staining Immunohistochemistry (dIHC) with EMA/Ki-67 better highlights neoplastic meningothelial cells compared with single-stain evaluation. Furthermore, the application of Digital Pathology provides quantitative digital data that allow a more accurate assessment of proliferation. Results: Ki-67 expression varied by grade, with digital image analysis (dIHC) showing high agreement with manual assessments. dIHC improved accuracy in evaluating diagnostic and proliferative markers within tumor samples. Conclusions: dIHC combined with DP can support and standardize the evaluation of the proliferative index in meningiomas in routine diagnostic practice.

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