Endocrine Abstracts

The aryl hydrocarbon receptor interacting protein gene has been mainly involved in the pathogenesis of GH/PRL-secreting pituitary adenomas (PA). We wished to study the significance of AIP expression in clinically non-functioning PA (NFPA).

Material and methods: 48 NFPA -27 gonadotroph (GnPA), 21 null cell (ncPA) – were studied for AIP, βFSH and cyclin D1 expression by real-time RT-PCR (qRT), compared with four normal post-mortem pituitaries (NP). 36 (21 GnPA, 15 NC) were also studied by semi-quantitative immunohistochemistry (AIP-IHC score: 0–6). Median values are given and data were analysed by non-parametric statistical analysis.

Results: Data from qRT-PCR in NFPA suggested AIP overexpression in 15/27 GnPA (55.5%) vs 2/21 ncPA (9.5%) and underexpression in 1/27 GnPA (3.7%) vs 4/21 ncPA (19%), respectively (P=0.00028). The AIP: βactin ratio was significantly higher in GnPA than in ncPA (6.7 vs 2.6, P=0.0008), with a strong linear correlation between AIP: βactin and βFSH: βactin ratios (R=0.49, P=0.0004). The AIP-IHC score significantly correlated with AIP gene expression (P=0.010) and was significantly higher in GnPA than in ncPA (3 vs 2, P=0.027). No significant correlation was found between AIP expression and tumour invasiveness. However, the AIP: βactin ratio was significantly lower in NFPA with a huge suprasellar extension (SSE grade C/D) or a high Ki67 index (≥3%) (2.33 vs 4.23 for SSE, P=0.042 and 2.49 vs 6.38 for Ki67, P=0.0165), suggesting that AIP is not involved in tumour aggressiveness. Data from qRT-PCR suggested overexpression of CyclinD1 in most NFPA (88.5% GnPA, 78.9% ncPA), although the CyclinD1: βactin ratio was lower in the presence of a high Ki67 index (17.8 vs 1.6, P=0.037). A significant linear correlation was observed between AIP and CyclinD1 expression (R=0.47, P=0.001), especially in GnPA (R=0.52, P=0.006).

Conclusion: AIP expression in NFPA is strongly associated with the gonadotroph phenotype and may be induced by extracellular factors driving CyclinD1 overexpression.