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Variable somatostatin receptor subtype expression in 151 primary pheochromocytomas and paragangliomas.

ABSTRACT: Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are neuroendocrine tumors that express somatostatin receptors (SSTRs), a phenomenon that constitutes a basis for tumor imaging and treatment with somatostatin analogues and peptide receptor radionuclide therapy. We studied the immunohistochemical expression of SSTR1-5 in 151 primary tumors, including 14 metastasized and 16 SDHB-deficient tumors. SSTR2 and SSTR3 were most abundantly present in these tumors, whereas the tumors were mostly negative for SSTR1, SSTR4, and SSTR5. All metastasized PGLs (9/9), but only one metastasized PHEO (1/5), were strongly SSTR2 positive. SSTR3 expression was lower in metastatic tumors and tumors with a high proliferation rate (MIB1 ≥ 5%), but tumors had variable individual SSTR profiles. No correlation was found between SDHB status and SSTR expression. Our results suggest that new SSTR analogues with affinity for several SSTRs could be relevant for a subgroup of patients with these tumors. Better knowledge of tumor SSTR profiles could open the door for personalized imaging and treatment in the future. Because SSTR profiles vary in PHEOs and PGLs, individual analysis is required for each tumor.

SUBMITTER: Leijon H

PROVIDER: S-EPMC8192062 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Expression data from primary and hereditary pheochromocytomas (PHEOs) and paragangliomas (PGLs)

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Expression data from benign and malignant pheochromocytomas and paragangliomas

Project description:Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine, usually benign tumors. Currently, for these neoplasms the only reliable criterion of malignancy is the presence of metastases. The aim of the present study was to identify molecular markers that can distinguish malignant from benign PPGL. An mRNA expression array was performed on 40 benign and 11 malignant PPGL. Genes showing a significantly different expression between benign and malignant PPGL with a ratio ? 4 were selected. Differentially expressed genes were confirmed by qRT-PCR and subsequently tested in an independent validation series (4 benign and 4 malignant) by qRT-PCR. Finally, immunohistochemistry was performed for the validated genes on Tissue Micro Arrays, which included 100 PPGL (87 benign and 13 malignant). Ten genes, which were significantly differentially expressed between benign and malignant tumors (False Discovery Rates <0.05), were selected from the mRNA expression array data. Differential expression of Interleukin 13 Receptor Alpha 2 and Contactin 4 was confirmed (p<0.05) and validated by qRT-PCR. However, at the protein level, only Contactin 4 appeared to be significantly overexpressed in malignant tumors (58% in malignant versus 17% in benign; p<0.05). No difference in the immunohistochemical staining for Interleukin 13 Receptor Alpha 2 was observed between benign and malignant PPGL. Contactin 4 expression appears to be associated with malignancy in pheochromocytomas and paragangliomas, and may be predictive of malignant behavior.

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