Increased SSTR2A and SSTR3 expression in succinate dehydrogenase-deficient pheochromocytomas and paragangliomas

Abstract

Many neuroendocrine tumors, including pheochromocytomas (PCs) and paragangliomas (PGLs), express one or more somatostatin receptors (SSTR1-5). A number of studies have reported SSTR expression in PCs and PGLs. However, receptor expression patterns have been conflicting, and until recently, specific monoclonal antibodies were not available against SSTR1-5.

The aim of this study was to compare SSTR1-5 expression in succinate dehydrogenase (SDH)-deficient PCs and PGLs (defined as having absent SDHB immunostaining) to those tumors with normal SDHB staining.

Immunohistochemistry for SDHB and SSTR1-5 was performed using specific monoclonal antibodies on archived formalin-fixed, paraffin-embedded tissue from patients who had undergone surgery for PC or PGLs.

A total of 182 PC/PGLs were included (129 adrenal, 44 extra-adrenal, 9 metastases); 32 tumors were SDH deficient, whereas 150 tumors had positive SDHB staining.

SDH-deficient tumors were more likely to demonstrate moderate or strong staining for SSTR2A and SSTR3 when compared with SDH-sufficient tumors (91% versus 49% [P < .0001] and 50% versus 21% [P = .0008], respectively).

Immunostaining for the other SSTRs was not different between SDH-deficient and tumors with preserved SDHB staining. SSTR2A and SSTR3 are more likely to be expressed in SDH-deficient PC/PGLs as compared with tumors demonstrating normal SDHB staining pattern.

These findings suggest that the role of somatostatin analogue therapy (unlabeled or radiolabeled) should be reexamined in the context of the underlying SDHB immunohistochemistry pattern.

 

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