Immunohistochemical assessment and clinical, histopathologic, and molecular correlates of membranous somatostatin type-2A receptor expression in high-risk pediatric central nervous system tumors
Introduction177Lu-DOTATATE, a radionuclide therapy that binds somatostatin type-2A receptors (SST2A), has demonstrated efficacy in neuroendocrine tumors and evidence of central nervous system (CNS) penetration, supporting potential expansion within pediatric neuro-oncology. Understanding the prevale...
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.996489/full |
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| author | Margot A. Lazow Margot A. Lazow Margot A. Lazow Christine Fuller Andrew T. Trout Andrew T. Trout Andrew T. Trout Joseph R. Stanek Joseph R. Stanek Jaime Reuss Brian K. Turpin Brian K. Turpin Sara Szabo Sara Szabo Ralph Salloum Ralph Salloum |
| author_facet | Margot A. Lazow Margot A. Lazow Margot A. Lazow Christine Fuller Andrew T. Trout Andrew T. Trout Andrew T. Trout Joseph R. Stanek Joseph R. Stanek Jaime Reuss Brian K. Turpin Brian K. Turpin Sara Szabo Sara Szabo Ralph Salloum Ralph Salloum |
| author_sort | Margot A. Lazow |
| collection | DOAJ |
| description | Introduction177Lu-DOTATATE, a radionuclide therapy that binds somatostatin type-2A receptors (SST2A), has demonstrated efficacy in neuroendocrine tumors and evidence of central nervous system (CNS) penetration, supporting potential expansion within pediatric neuro-oncology. Understanding the prevalence of SST2A expression across pediatric CNS tumors is essential to identify patients who may benefit from somatostatin receptor-targeted therapy and to further elucidate the oncogenic role of SST2A.MethodsSST2A immunohistochemistry (IHC) was performed on tumor specimens and interpreted by an experienced pathologist (blinded), utilizing semi-quantitative scoring of membranous expression within viable tumor. Immunoreactive cell percentage was visually scored as 0 (none), 1 (<10%), 2 (10-50%), 3 (51-80%), or 4 (>80%). Staining intensity was scored as 0 (none), 1 (weak), 2 (moderate), or 3 (strong). Combined scores for each specimen were calculated by multiplying percent immunoreactivity and staining intensity values (Range: 0-12).ResultsA total of 120 tumor samples from 114 patients were analyzed. Significant differences in SST2A IHC scores were observed across histopathologic diagnoses, with consistently high scores in medulloblastoma (mean ± SD: 7.5 ± 3.6 [n=38]) and meningioma (5.7 ± 3.4 [n=15]), compared to minimal or absent expression in ATRT (0.3 ± 0.6 [n=3]), ETMR (1.0 ± 0 [n=3]), ependymoma (grades I-III; 0.2 ± 0.7 [n=27]), and high-grade glioma (grades III-IV; 0.4 ± 0.7 [n=23]). Pineoblastoma (3.8 ± 1.5 [n=4]) and other embryonal tumors (2.0 ± 4.0 [n=7]) exhibited intermediate, variable expression. Among medulloblastomas, SST2A IHC scores were higher in non-SHH (8.5 ± 3.1) than SHH (5.0 ± 3.3) molecular subgroups (p=0.033). In a subset of paired primary and recurrent specimens from four patients, SST2A IHC scores remained largely unchanged.DiscussionHigh membranous SST2A expression was demonstrated in medulloblastoma, meningioma, and some rarer embryonal tumors with potential diagnostic, biologic, and therapeutic implications. Somatostatin receptor-targeted therapy such as 177Lu-DOTATATE deserves further investigation in these highly SST2A-expressing pediatric CNS tumors. |
| first_indexed | 2024-04-12T08:50:36Z |
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| last_indexed | 2024-04-12T08:50:36Z |
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| series | Frontiers in Oncology |
| spelling | doaj.art-60242f28506e4ece8ba94e9bad7c32352022-12-22T03:39:36ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-11-011210.3389/fonc.2022.996489996489Immunohistochemical assessment and clinical, histopathologic, and molecular correlates of membranous somatostatin type-2A receptor expression in high-risk pediatric central nervous system tumorsMargot A. Lazow0Margot A. Lazow1Margot A. Lazow2Christine Fuller3Andrew T. Trout4Andrew T. Trout5Andrew T. Trout6Joseph R. Stanek7Joseph R. Stanek8Jaime Reuss9Brian K. Turpin10Brian K. Turpin11Sara Szabo12Sara Szabo13Ralph Salloum14Ralph Salloum15Pediatric Neuro-Oncology Program, Nationwide Children’s Hospital, Columbus, OH, United StatesDepartment of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United StatesCancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United StatesDepartment of Pathology, Upstate Medical University, Syracuse, NY, United StatesDepartment of Radiology and Medical Imaging, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United StatesDepartment of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesPediatric Neuro-Oncology Program, Nationwide Children’s Hospital, Columbus, OH, United StatesDepartment of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United StatesDepartment of Pathology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United StatesCancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United StatesDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesDepartment of Pathology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United StatesPediatric Neuro-Oncology Program, Nationwide Children’s Hospital, Columbus, OH, United StatesDepartment of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United StatesIntroduction177Lu-DOTATATE, a radionuclide therapy that binds somatostatin type-2A receptors (SST2A), has demonstrated efficacy in neuroendocrine tumors and evidence of central nervous system (CNS) penetration, supporting potential expansion within pediatric neuro-oncology. Understanding the prevalence of SST2A expression across pediatric CNS tumors is essential to identify patients who may benefit from somatostatin receptor-targeted therapy and to further elucidate the oncogenic role of SST2A.MethodsSST2A immunohistochemistry (IHC) was performed on tumor specimens and interpreted by an experienced pathologist (blinded), utilizing semi-quantitative scoring of membranous expression within viable tumor. Immunoreactive cell percentage was visually scored as 0 (none), 1 (<10%), 2 (10-50%), 3 (51-80%), or 4 (>80%). Staining intensity was scored as 0 (none), 1 (weak), 2 (moderate), or 3 (strong). Combined scores for each specimen were calculated by multiplying percent immunoreactivity and staining intensity values (Range: 0-12).ResultsA total of 120 tumor samples from 114 patients were analyzed. Significant differences in SST2A IHC scores were observed across histopathologic diagnoses, with consistently high scores in medulloblastoma (mean ± SD: 7.5 ± 3.6 [n=38]) and meningioma (5.7 ± 3.4 [n=15]), compared to minimal or absent expression in ATRT (0.3 ± 0.6 [n=3]), ETMR (1.0 ± 0 [n=3]), ependymoma (grades I-III; 0.2 ± 0.7 [n=27]), and high-grade glioma (grades III-IV; 0.4 ± 0.7 [n=23]). Pineoblastoma (3.8 ± 1.5 [n=4]) and other embryonal tumors (2.0 ± 4.0 [n=7]) exhibited intermediate, variable expression. Among medulloblastomas, SST2A IHC scores were higher in non-SHH (8.5 ± 3.1) than SHH (5.0 ± 3.3) molecular subgroups (p=0.033). In a subset of paired primary and recurrent specimens from four patients, SST2A IHC scores remained largely unchanged.DiscussionHigh membranous SST2A expression was demonstrated in medulloblastoma, meningioma, and some rarer embryonal tumors with potential diagnostic, biologic, and therapeutic implications. Somatostatin receptor-targeted therapy such as 177Lu-DOTATATE deserves further investigation in these highly SST2A-expressing pediatric CNS tumors.https://www.frontiersin.org/articles/10.3389/fonc.2022.996489/fullsomatostatin receptorSST2Aimmunohistochemistrypediatric CNS tumorsembryonal tumorsmedulloblastoma |
| spellingShingle | Margot A. Lazow Margot A. Lazow Margot A. Lazow Christine Fuller Andrew T. Trout Andrew T. Trout Andrew T. Trout Joseph R. Stanek Joseph R. Stanek Jaime Reuss Brian K. Turpin Brian K. Turpin Sara Szabo Sara Szabo Ralph Salloum Ralph Salloum Immunohistochemical assessment and clinical, histopathologic, and molecular correlates of membranous somatostatin type-2A receptor expression in high-risk pediatric central nervous system tumors Frontiers in Oncology somatostatin receptor SST2A immunohistochemistry pediatric CNS tumors embryonal tumors medulloblastoma |
| title | Immunohistochemical assessment and clinical, histopathologic, and molecular correlates of membranous somatostatin type-2A receptor expression in high-risk pediatric central nervous system tumors |
| title_full | Immunohistochemical assessment and clinical, histopathologic, and molecular correlates of membranous somatostatin type-2A receptor expression in high-risk pediatric central nervous system tumors |
| title_fullStr | Immunohistochemical assessment and clinical, histopathologic, and molecular correlates of membranous somatostatin type-2A receptor expression in high-risk pediatric central nervous system tumors |
| title_full_unstemmed | Immunohistochemical assessment and clinical, histopathologic, and molecular correlates of membranous somatostatin type-2A receptor expression in high-risk pediatric central nervous system tumors |
| title_short | Immunohistochemical assessment and clinical, histopathologic, and molecular correlates of membranous somatostatin type-2A receptor expression in high-risk pediatric central nervous system tumors |
| title_sort | immunohistochemical assessment and clinical histopathologic and molecular correlates of membranous somatostatin type 2a receptor expression in high risk pediatric central nervous system tumors |
| topic | somatostatin receptor SST2A immunohistochemistry pediatric CNS tumors embryonal tumors medulloblastoma |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.996489/full |
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