Immununohistochemical Analysis of Progesterone Receptor and Ki-67 in Meningioma: A Cross-sectional Study

Abstract

Introduction: The most common primary intracranial tumour is meningioma. It occurs mostly in middle-aged to elderly individuals. Differentiating meningiomas from other intracranial lesions and properly grading them is often a challenging task for pathologists. Meningiomas can cause significant morbidity, mortality, and recurrence, even after complete excision, which may lead to repeat operations and ultimately reduced survival rates. Meningiomas are categorised by the World Health Organisation (WHO) into three grades, primarily based on subjective methods that consider morphology, mitotic figures, and necrosis. Proliferative activity can also be assessed to some extent using these parameters. To minimise subjective biases, it is advisable to use Progesterone Receptor (PR) expression and Ki-67 Labelling Index (LI)-when feasible-as predictive markers for understanding tumour behaviour, which can also be useful for individualised management. Aim: To investigate the status of PR expression and the Ki-67 index in meningioma, along with their associations with age, gender, risk factors, histological types, and grading of meningiomas. Materials and Methods: The present study was a Institution-based retrospective cross-sectional analysis conducted in the Department of Pathology in collaboration with the Department of Neurosurgery at Nil Ratan Sircar Medical College and Hospital (NRSMCH), Kolkata, West Bengal, India. The study examined the correlation of PR expression with Ki-67 LI in 50 diagnosed cases of meningiomas following a retrospective review of all cases from March 2022 to February 2023. Primary ready-to-use antibodies were employed immunohistochemically to assess the immunostatus of these markers for prognostication of meningiomas. For statistical analysis, Statistical Package for Social Sciences (SPSS) version 27.0 was utilised, applying mean, Standard Deviation (SD), Analysis of Variance (ANOVA), and Chi-square testing. A p-value of less than 0.05 was considered statistically significant. Results: Among the 50 cases, there were 30 Females (F) and 20 Males (M), resulting in a ratio of M:F=1:1.5. The percentage distribution of grade I, grade II, and grade III cases was 37 (74%), 10 (20%), and 3 (6%), respectively. Meningothelial tumours were the predominant histomorphological subtype, accounting for 14 cases (37.83%). PR positivity was observed in 35 cases (70%). Most of the grade I cases demonstrated PR positivity (26 out of 37 cases, or 70.27%) and a low mean Ki-67 value of 4.16%. In contrast, the grade III cases primarily exhibited absent to weakly positive PR status (3 out of 3, or 100%) with a high Ki-67 value of 11%. The mean Ki-67 value was higher in PR-negative cases (n=15), at 7.18% with an SD of 4.26, while it was lower in PR-positive cases (n=35), with a mean of 3.64% and an SD of 4.17. Both PR expression and Ki-67 index showed a significant reduction and increase, respectively, with increasing WHO grades. The association of grade with PR and Ki-67 was significant (p-value=0.003 and p-value=0.004, respectively). An inverse correlation was observed between the Ki-67 index and PR score (R=-0.7561). The combined PR status and Ki-67 expression had a sensitivity of 96.67%, specificity of 100%, and an overall accuracy of 97.78%. Conclusion: The results indicate that middle-aged females are more likely to develop meningiomas, with the most common site being intracranial. Grade I tumours were the most prevalent, particularly the meninogothelial subtype. PR expression decreased, and Ki-67 index increased with higher grades. The mean Ki-67 value was greater in grade III meningiomas and PR-negative cases. The association between tumour grade and PR and Ki-67 was significant. The study of PR and Ki-67 immunohistochemical staining proved to be valuable supplements to routine histopathological assessments; thus, management strategies should be individualised.

Keywords

• immunostains
• intracranial
• grade
• tumours