J Korean Neurosurg Soc.  2021 Jan;64(1):100-109. 10.3340/jkns.2020.0071.

Analysis of Mutant Isocitrate Dehydrogenase 1 Immunoexpression, Ki-67 and Programmed Death Ligand 1 in Diffuse Astrocytic Tumours : Study of Single Center in Bandung, Indonesia

• Bolly HMB
• Faried A
• Hermanto Y
• Lubis BP
• Tjahjono FP
• Hernowo BS
• Arifin MZ

• KMID: 2510764
• DOI: http://doi.org/10.3340/jkns.2020.0071

Abstract

Objective
: Diffuse astrocytic tumour (DAT) is a diffuse infiltrative astrocytoma tumour accompanied by molecular parameters such as the presence or absence of isocitrate dehydrogenase (IDH) gene mutations. Ki-67 is a marker for DAT proliferation, while programmed death ligand 1 (PD-L1) indicates an immune evasion mechanism. This study aimed to analyze the correlation among mutant IDH1 R132H, Ki-67, and PD-L1 immunoexpression in the DAT.
Methods
: A cross-sectional study was carried out on 30 paraffin blocks of DAT cases. Paraffin block samples consist of grade II (n=14), grade III (n=8), and grade IV (n=8). In this study, the immunohistochemistry-staining of mutant IDH1 R132H, Ki-67, and PD-L1 were carried out to determine the frequency of DAT with IDH1 mutations.
Results
: Our study shown the frequency of IDH1 mutations in grade II 50.0% (7/14), grade III 37.5% (3/8), and grade IV 12.5% (1/8). Our study also showed a difference in Ki-67 and PD-L1 expression between each the degree of DAT histopathology (p=0.0001 and p=0.002, respectively). There was an association between both mutant IDH1 R132H, and Ki-67 with PD-L1 expression in DAT (p=0.0087 and p=0.0049, respectively).
Conclusion
: DAT with the mutant IDH1 is frequently observed in grade II and small number of grade III. The expression of wild type IDH1, Ki-67, and PD-L1 were found to be higher in high grade DAT (grade III and grade IV). There is a correlation between each of mutant IDH1 status and Ki-67 with PD-L1 expression in DAT.

Keyword

Diffuse astrocytic tumor; Histopathology grade; Mutant IDH1 R132H; Ki-67; PD-L1

Figure

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  Fig. 1. Illustration depicting layers of suprasellar structures associated with pituitary adenoma (asterisk) (sagittal section). Pituitary adenoma grows toward the chiasmatic cistern through the medial opening of the diaphragma sellae (arrowheads), which is extention of dura mater (double arrow), forming the roof of the sellar turcica. Note that the arachnoid membrane (arrow) in the cistern is elevated and attached to the tumor surface due to the upward growth of the pituitary adenoma. Sphe. : sphenoid sinus.

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  Fig. 2. Boxplots and volumetric scatter plots of the variables compared to the degree of arachnoid membrane descent after tumor removal. The categorical variables are depicted with volumetric scatter plots, and continuous variables are presented with boxplots. A : Boxplot of tumor height compared to the degree of arachnoid membrane descent; no correlation (r=0.091, p=0.588). B : Boxplot of the height of the suprasellar extension on pre-operative MR imaging with the degree of arachnoid membrane descent showed a trend towards a correlation, but this was not statistically significant (r=0.285, p=0.083). C : Volumetric scatter plot of tumor composition on pre-operative T2WI compared to the degree of arachnoid membrane descent revealed a strong positive correlation (r=0.571, p<0.01). D : The displacement of the pituitary gland and stalk on pre-operative MR imaging compared to arachnoid membrane descent is presented with the volumetric scatter plot, demonstrating no correlation (r=0.0008, p=0.962). E and F : Boxplots of the area of the medial opening and DS compared to arachnoid membrane descent. Both areas were correlated with the degree of arachnoid membrane descent (area of the medial opening, r=0.340, p=0.037; area of DS, r=0.348, p=0.032), although the ratio of the two areas (G) was not (r=0.241, p=0.145). H : The intra-operative consistency of the tumor depicted with a volumetric scatter plot was not correlated with arachnoid membrane descent (r=-0.299, p=0.073). T2WI : T2-weighted images, DS : diaphragma sellae, MR : magnetic resonance.

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  Fig. 3. Illustrations depicting the degree of arachnoid membrane descent after removal of the tumor with representative cases and corresponding T2WI. A : No descent, although oscillation of the roof structure was verified, it remained at its location without descent. The endoscopic view shows that a whitish membrane-like material covers the DS and is likely to prevent the descent of the upper structure. T2WI of the tumor in this patient exhibits prominent mixed signal intensity. B : Minimal descent, the roof structure descended minimally. There is also a sheet-like whitish patch beneath the upper structure with a vacant space filled by the tumor on the intra-operative photograph. T2WI in this patient showed a cystic component with some mixed signal intensity. C : Moderate, the structure descended as much as the height of the suprasellar extension through the medial opening and its corresponding intra-operative endoscopic view. T2WI shows little mixed signal intensity. D : Marked descent, the structure descended more than the height of extension, and the descended arachnoid membrane is swollen and appears transparent. The intra-operative view shows the arachnoid membrane descended under the pituitary fossa, and homogenous signal intensity is exhibited on T2WI. DS : diaphragma sellae, T2WI : T2-weighted images.

Reference

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