Quantitative Analysis of Somatostatin and Dopamine Receptors Gene Expression Levels in Non-functioning Pituitary Tumors and Association with Clinical and Molecular Aggressiveness Features

Abstract

The primary treatment for non-functioning pituitary tumors (NFPTs) is surgery, but it is often unsuccessful. Previous studies have reported that NFPTs express receptors for somatostatin (SST_1-5) and dopamine (DRDs) providing a rationale for the use of dopamine agonists and somatostatin analogues. Here, we systematically assessed SST_1-5 and DRDs expression by real-time quantitative PCR (RT-qPCR) in a large group of patients with NFPTs (n = 113) and analyzed their potential association with clinical and molecular aggressiveness features. SST_1-5 expression was also evaluated by immunohistochemistry. SST₃ was the predominant SST subtype detected, followed by SST₂, SST₅, and SST₁. DRD2 was the dominant DRD subtype, followed by DRD4, DRD5, and DRD1. A substantial proportion of NFPTs displayed marked expression of SST₂ and SST₅. No major association between SST_s and DRDs expression and clinical and molecular aggressiveness features was observed in NFPTs.

Keywords: dopamine receptor; invasion; non-functioning pituitary tumors; pituitary tumor; somatostatin receptor.

Figure 1

Somatostatin receptors (SSTs) and dopamine receptors (DRDs) expression in NFPTs. Expression profile of SSTs and DRDs in: (A) NFPTs, gonadotropin-storing adenomas, null cell adenomas and silent corticotroph adenomas; (B) only in gonadotropin-storing adenomas; (C) only in null cell adenomas; and, (D) only in silent corticotroph adenomas. mRNA expression levels were measured by quantitative RT-PCR. Copy numbers of each transcript was adjusted by the expression levels of a control gene (ACTB). Data are shown as mean ± SEM.

Figure 2

Immunohistochemical detection of somatostatin receptors (SSTs) in NFPTs assessed by immunohistochemistry. (A) Representative pictures of SST₂, SST₃ and SST₅ immunohistochemical scores in NFPTs. Score 1, no or only cytoplasmic immunoreactivity; score 2, membranous immunoreactivity in less than 50% of cells; score 3, membranous immunoreactivity in more than 50% of cells. Scale bar: 50 μm. (B) Percentage of NFPTs for immunohistochemistry (IHC) scores (SST₂, SST₃ and SST₅).

Figure 3

Accumulation of E-cadherin in NFPTs assessed by immunohistochemistry. (A) Representative pictures of E-cadherin immunohistochemical scores in NFPTs. Score 1, no or very low immunoreactivity; score 2, membranous immunoreactivity in less than 50% of cells; score 3, membranous immunoreactivity in more than 50% of cells. Scale bar: 100 μm. (B) Percentage of NFPTs for IHC scores. Score 1: 9.47%; score 2: 50.52% and score 3: 40%.