2023Applied immunohistochemistry & molecular morphologyRequires access

Practice of IDH1, ATRX, and P53 Immunohistochemistry in Integrated Diagnosis of Adult Diffuse Gliomas: Single Center Study

Zohreh Shabanzadeh nejabad, Hoda Mabroukzadeh kavari, Hana Saffar, Seyed Mohammad Tavangar, Salma Sefidbakht, Alireza Khoshnevisan, Ali Zare‐Mirzaie, Mohammad Vasei, Ensieh Jafari, Marjan Yaghmaii, Hiva Saffar

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Abstract

Diffuse gliomas exhibit different molecular and genetic profiles with a wide range of heterogeneity and prognosis. Recently, molecular parameters including ATRX, P53, and IDH mutation status or absence or presence of 1p/19q co-deletion have become a crucial part of the diagnosis of diffuse glioma. In the present study, we tried to analyze the routine practice of the above-mentioned molecular markers focusing on the IHC method in cases of adult diffuse gliomas to evaluate their utility in the integrated diagnosis of adult diffuse gliomas. In total, 134 cases of adult diffuse glioma were evaluated. Using the IHC method, 33,12, and 12 cases of IDH mutant Astrocytoma grade 2, 3, 4, and 45 cases of gliobalstoma, IDH wild type, were molecularly diagnosed. By adding the FISH study for 1p/19q co-deletion, 9 and 8 cases of oligodendroglioma grade 2 and 3 also were included. Two IDH mutant cases were negative for IDH1 in IHC but revealed a positive mutation in further molecular testing. Finally, we were not able to incorporate a complete integrated diagnosis in 16/134(11.94%) of cases. The main molecularly unclassified group was histologically high-grade diffuse glial tumors in patients less than 55 years old and negative IDH1 immunostaining. P53 was positive in 23/33 grade 2, 4/12 grade 3, and 7/12 grade 4 astrocytomas, respectively. Four out of 45 glioblastomas showed positive immunostain, and all oligodendrogliomas were negative. In conclusion, a panel of IHC markers for IDH1 R132H, P53, and ATRX significantly improves the molecular classification of adult diffuse gliomas in daily practice and can be used as a tool to select limited cases for co-deletion testing in the low resources area.

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Diffuse gliomas exhibit different molecular and genetic profiles with a wide range of heterogeneity and prognosis. Recently, molecular parameters including ATRX, P53, and IDH mutation status or absence or presence of 1p/19q co-deletion have become a crucial part of the diagnosis of diffuse glioma. In the present study, we tried to analyze the routine practice of the above-mentioned molecular markers focusing on the IHC method in cases of adult diffuse gliomas to evaluate their utility in the integrated diagnosis of adult diffuse gliomas. In total, 134 cases of adult diffuse glioma were evaluated. Using the IHC method, 33,12, and 12 cases of IDH mutant Astrocytoma grade 2, 3, 4, and 45 cases of gliobalstoma, IDH wild type, were molecularly diagnosed. By adding the FISH study for 1p/19q co-deletion, 9 and 8 cases of oligodendroglioma grade 2 and 3 also were included. Two IDH mutant cases were negative for IDH1 in IHC but revealed a positive mutation in further molecular testing. Finally, we were not able to incorporate a complete integrated diagnosis in 16/134(11.94%) of cases. The main molecularly unclassified group was histologically high-grade diffuse glial tumors in patients less than 55 years old and negative IDH1 immunostaining. P53 was positive in 23/33 grade 2, 4/12 grade 3, and 7/12 grade 4 astrocytomas, respectively. Four out of 45 glioblastomas showed positive immunostain, and all oligodendrogliomas were negative. In conclusion, a panel of IHC markers for IDH1 R132H, P53, and ATRX significantly improves the molecular classification of adult diffuse gliomas in daily practice and can be used as a tool to select limited cases for co-deletion testing in the low resources area.

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Available abstract

Diffuse gliomas exhibit different molecular and genetic profiles with a wide range of heterogeneity and prognosis. Recently, molecular parameters including ATRX, P53, and IDH mutation status or absence or presence of 1p/19q co-deletion have become a crucial part of the diagnosis of diffuse glioma. In the present study, we tried to analyze the routine practice of the above-mentioned molecular markers focusing on the IHC method in cases of adult diffuse gliomas to evaluate their utility in the integrated diagnosis of adult diffuse gliomas. In total, 134 cases of adult diffuse glioma were evaluated. Using the IHC method, 33,12, and 12 cases of IDH mutant Astrocytoma grade 2, 3, 4, and 45 cases of gliobalstoma, IDH wild type, were molecularly diagnosed. By adding the FISH study for 1p/19q co-deletion, 9 and 8 cases of oligodendroglioma grade 2 and 3 also were included. Two IDH mutant cases were negative for IDH1 in IHC but revealed a positive mutation in further molecular testing. Finally, we were not able to incorporate a complete integrated diagnosis in 16/134(11.94%) of cases. The main molecularly unclassified group was histologically high-grade diffuse glial tumors in patients less than 55 years old and negative IDH1 immunostaining. P53 was positive in 23/33 grade 2, 4/12 grade 3, and 7/12 grade 4 astrocytomas, respectively. Four out of 45 glioblastomas showed positive immunostain, and all oligodendrogliomas were negative. In conclusion, a panel of IHC markers for IDH1 R132H, P53, and ATRX significantly improves the molecular classification of adult diffuse gliomas in daily practice and can be used as a tool to select limited cases for co-deletion testing in the low resources area.

Key concepts: ATRX, IDH1, Oligodendroglioma, Immunostaining, Immunohistochemistry, Astrocytoma, Medicine, Pathology

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