Immunohistochemical assessment and clinical, histopathologic, and molecular correlates of membranous somatostatin type-2A receptor expression in high-risk pediatric central nervous system tumors

Margot A Lazow; Christine Fuller; Andrew T Trout; Joseph R Stanek; Jaime Reuss; Brian K Turpin; Sara Szabo; Ralph Salloum

doi:10.3389/fonc.2022.996489

Immunohistochemical assessment and clinical, histopathologic, and molecular correlates of membranous somatostatin type-2A receptor expression in high-risk pediatric central nervous system tumors

Front Oncol. 2022 Nov 17:12:996489. doi: 10.3389/fonc.2022.996489. eCollection 2022.

Authors

Margot A Lazow^{1

2

3}, Christine Fuller⁴, Andrew T Trout^{5

6

7}, Joseph R Stanek^{1

2}, Jaime Reuss⁸, Brian K Turpin^{3

7}, Sara Szabo^{7

8}, Ralph Salloum^{1

2}

Affiliations

¹ Pediatric Neuro-Oncology Program, Nationwide Children's Hospital, Columbus, OH, United States.
² Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United States.
³ Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
⁴ Department of Pathology, Upstate Medical University, Syracuse, NY, United States.
⁵ Department of Radiology and Medical Imaging, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
⁶ Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
⁷ Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
⁸ Department of Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.

Abstract

Introduction: ¹⁷⁷Lu-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.

Methods: SST2A 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).

Results: A 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.

Discussion: High 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.

Keywords: DOTATATE; SST2A; embryonal tumors; immunohistochemistry; medulloblastoma; pediatric CNS tumors; somatostatin receptor; somatostatin receptor-targeted therapy.