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

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.

Immunohistochemical Expression of PD-L1 and IDH1 with Detection of MGMT Promoter Methylation in Astrocytoma

“…In this study, our findings showed that PD-L1 was identified in 81.73% of astrocytoma cases, while IDH1 was detected in 73.3%. Similarly, both Xue et al, (2017) and Bolly et al, (2021) reported expression rate of PD-L1 (78% and 70%, respectively), which was close to our results. As well, Nazari et al, (2020), andBolly et al, (2021), reported higher PD-L1 expression among the high-grade group (100% and 87.5%, respectively).…”

“…Similarly, both Xue et al, (2017) and Bolly et al, (2021) reported expression rate of PD-L1 (78% and 70%, respectively), which was close to our results. As well, Nazari et al, (2020), andBolly et al, (2021), reported higher PD-L1 expression among the high-grade group (100% and 87.5%, respectively). A lower rate of IDH1 mutation was reported by Nazari et al (2020) (20%) and July et al, (2020) (17%), which could be attributed to the larger sample size.…”

“…Higher PD-L1 expression was also detected in IDH1 mutant lowgrade cases (66.7%) and IDH1 mutant high-grade cases (80%) in relation to IDH1 NOS cases. On the contrary, Wang et al, (2016), Berghoff et al, (2015), and Bolly et al, (2021) reported that IDH wild-type astrocytoma is associated with significantly higher PDL1 expression in all grades of astrocytoma. This discrepancy could be attributed to the that these studies used different both anti IDH1 clones and anti-PD-L1 clones, in addition to the high prevalence of IDH mutation in our cases.…”

“…Moreover, there was no significant association between the recurrence rate and PD-L1 expression (P = 0.317), IDH1 expression (P=0.652), or MGMT promoter methylation (P= 1.00). Bolly et al,(2021) reported that most of the high-grade studied astrocytoma cases were IDH1 wild. This could be explained by most of our cases may arise from lower-grade tumors, which unfortunately were unavailable in our records.…”

Current Immunotherapeutic Approaches for Malignant Gliomas

“…The annual incidence of malignant gliomas is about 5 cases per 100,000 person-years [ 1 ]. Astrocytic tumors (pilocytic astrocytoma, diffuse astrocytoma, anaplastic astrocytoma, glioblastoma, or all other gliomas) account for 76.4% of all gliomas [ 2 ].…”