Digital Quantification of Progesterone Receptor Expression in Meningiomas: Associations with WHO Grade and Clinicopathological Features

TL;DR

This study uses digital pathology to objectively measure progesterone receptor levels in meningiomas and finds links to tumor grade and growth markers.

Contribution

The study applies an FDA-approved digital scoring algorithm, originally for breast cancer, to meningiomas and validates its utility in this context.

Findings

Digital PR H-scores decrease with higher WHO grades of meningiomas.

PR expression is inversely correlated with Ki-67 index and mitotic count.

Convexity meningiomas show higher PR scores than skull base and spinal tumors.

Abstract

Objective:
Progesterone receptor (PR) expression is a well-recognized marker in meningiomas, but manual immunohistochemical assessment is subjective and prone to variability. Digital pathology offers objective and reproducible quantification. Despite the availability of FDA-cleared digital PR scoring algorithms in some tumors like those of the breast, their implementation in meningiomas and systematic evaluation of their correlations with clinicopathological features remain scarce.

Material and Methods:
We retrospectively analyzed 129 meningioma cases resected between 2018 and 2024. Digital PR expression was quantified using the FDA-cleared Ventana uPath PR 1E2 algorithm, originally developed for breast carcinoma. Subsequently, tumors were stratified by age, sex, WHO grade, histological subtype, and localization, while Ki-67 index and mitotic counts were also recorded. Associations with digital PR H-scores were evaluated using non-parametric tests, correlation analysis, and ordinal logistic regression.

Results:
Digital PR H-scores progressively decreased across WHO grades, with Grade 1 tumors showing the highest values, followed by Grade 2 and Grade 3 (p=0.002). PR expression was inversely correlated with proliferative markers, including Ki-67 index (ρ = –0.42, p<0.001) and mitotic count (ρ = –0.35, p<0.01). No significant differences were observed by age or sex. Convexity meningiomas tended to have higher scores than skull base and spinal tumors.

Conclusion:
Digital PR H-score assessment confirmed the inverse association between PR expression and WHO grade, as well as its correlation with proliferative activity. Using an FDA-cleared algorithm originally developed for breast carcinoma, this method provides objective and reproducible evaluation in meningiomas.

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