Expression Profiling of IDH, p53, ATRX, and KI-67 Immunostains as Potential Grid for Molecular Subtyping of Adult Diffuse Gliomas from Pakistan

Abstract

Abstract Background The classification of gliomas is changing profoundly and has been shifted from histological criteria only; to morphological and molecular markers. The routine everyday approach nowadays for diagnosing diffuse gliomas begins with immunohistochemistry (IHC) for IDH1, ATRX, and p53, as these substitute molecular testing for classification. Moreover, the Ki-67 immunomarker is a useful accessory marker for the proliferative activity and hence grading of these tumors. Keeping in mind the growing importance of molecular information in CNS tumor classification and the use of integrated diagnosis according to the new WHO Classification we undertook this immunohistochemical study for the integrated diagnosis of adult diffuse gliomas in our setup. Material & Method In this study, 92 prospective cases of adult diffuse gliomas were included from January 2018 to June 2021. We analyzed the IDH1, ATRX, and p53 status by immunohistochemistry (IHC) and analyzed the results in correlation to histological type, grade, and among these molecular markers. Result IDH R132H mutation, ATRX loss, and p53 mutation were mostly accompanied by astrocytoma in the current study. For IDH gene mutation, grade 2 and 3 patients (80%) have a higher positive rate than grade 4 (20%); for P53 gene mutation, grade 2 and 3 patients (77%) have a higher positive rate than grade 4 (22.6%). ATRX loss in astrocytomas was strongly associated with IDH1-R132H (p = 0.001) and p53 (p = 0.000). Among 31 glial tumors with nuclear ATRX loss, 23 (74%) had an IDH1 mutation and 19 (61%) had a p53 mutation. Ki-67 labeling index (LI) was above 5% in more than 90% of high-grade gliomas histologically and is associated with increasing WHO grade (p = < 0.000). Conclusion IDH1 p53, ATRX, and Ki67 markers can successfully be used to characterize diffuse gliomas into molecularly defined groups in most cases. IDH1 mutations together with ATRX loss and p53 mutation are common in astrocytomas grade 2–4, while they are rare in glioblastoma. IDH1 mutations without ATRX loss and p53 mutation characterized oligodendrogliomas. Moreover, this IHC panel is not only helpful in evaluating astrocytic versus oligodendroglial lineage, but in identifying the presence of oncoproteins which help in predicting the prognosis and therapeutic implications of the patients.