Somatostatin receptor 2A protein expression characterizes anaplastic oligodendrogliomas with favorable outcome

Abstract

Diffuse gliomas are classified according to the 2016 WHO Classification of Tumors of the Central Nervous System, which now defines entities by both histology and molecular features. Somatostatin receptor subtype 2A (SSTR2A) expression has been reported in various solid tumors as associated with favorable outcomes. Its expression has been reported in gliomas with uncertain results regarding its prognostic value. The objective of this study was to assess the prognostic impact of SSTR2A protein expression in a large cohort of grade III and IV gliomas classified according to the updated 2016 WHO classification. We further validated our result with an independent cohort of low grade glioma using dataset generated by The Cancer Genome Atlas (TCGA) Research Network.We analyzed clinical and molecular data from 575 patients. SSTR2A protein expression was evaluated using immunohistochemistry on tissue microarrays. High expression of SSTR2A protein associated with the anaplastic oligodendroglioma IDH-mutant and 1p/19q-codeleted subgroup (p < 0.001). Among these tumors, SSTR2A protein expression was significantly associated with a lower proliferative index, the absence of microvascular proliferation and the absence of necrosis (p < 0.001). Furthermore SSTR2A protein expression associated with better overall survival (p = 0.007) and progression-free survival (p = 0.01) in both univariate and multivariate analysis when adjusted by the age, the presence of necrosis and the mitotic index. Similar results were obtained regarding SSTR2 mRNA expression in the TCGA low grade glioma, subtype IDH-mutant and 1p/19q-codeleted, dataset.SSTR2A might represent an attractive biomarker and therapeutic target in anaplastic oligodendroglioma IDH-mutant and 1p/19q-codeleted specific subgroup. Understanding the implicated molecular pathways may represent a step forward to improve therapeutic approaches.

Keywords: Biomarker; Glioma; Somatostatin receptor subtype 2A (SSTR2A); Therapeutic target.

Fig. 1

Immunohistochemical staining of SSTR2A protein in anaplastic oligodendroglioma IDH-mutant and 1p/19q-codeleted (a) Negative staining (IRS = 0) (b) Weak staining intensity (score = 1) in 20% of the cells (score = 2) corresponding to positive cases with low expression (IRS = 3) (c) High staining intensity (score = 3) in 100% of the cells (score = 4) corresponding to positive cases with high expression (IRS = 12)

Fig. 2

Distribution of SSTR2A protein expression according to tumor subtype Abbreviations: AIII IDHwt, Anaplastic astrocytoma IDH-wildtype; GB IDHwt, Glioblastoma IDH-wildtype; AIII IDHmut, Anaplastic astrocytoma IDH-mutant; GB IDHmut, Glioblastoma IDH-mutant; OIII, Anaplastic oligodendroglioma, IDH-mutant and 1p/19q-codeleted. *** = p < 0.001

Fig. 3

a Distribution of SSTR2A protein expression according to pathological groups in anaplastic oligodendrogliomas, IDH-mutant and 1p/19q-codeleted. Abbreviation: MVP, microvascular proliferation b Ki-67 labelling index according to SSTR2A protein expression among the anaplastic oligodendroglioma, IDH-mutant and 1p/19q-codeleted. *** = p < 0.001

Fig. 4

Overall survival and Progression-free survival according to SSTR2A protein expression in anaplastic oligodendroglioma, IDH-mutant and 1p/19q-codeleted. a No SSTR2A expression (IRS = 0) versus low SSTR2A expression (1 ≤ IRS < 4) versus high SSTR2A expression (IRS ≥ 4). b Negative (IRS = 0) versus positive (IRS ≥ 1) SSTR2A expression

Fig. 5

a Relation between SSTR2 mRNA expression and subtype in low grade glioma patients from TCGA cohort. b Overall survival according to SSTR2 mRNA expression in patients with IDH-mutant and 1p/19q-codeleted low grade gliomas from the TCGA cohort. *** = p < 0.001