Endocrine Abstracts

Introduction: Pituitary Neuroendocrine Tumor (PitNET) subtypes present functioning and silent variants but the silencing mechanisms are still unknown. One of the possible hypotheses could be a decrease in the expression of the specific adenohypophyseal hormone genes. The aim of the present study was to analyze the expression of adenohypophyseal hormone genes in a series of PitNETs, in order to evaluate differences between functioning and silent PitNET subtypes, taking into account demographic and radiological variables such as age, gender, tumor size and invasiveness.

Material and methods: Molecular analysis was performed on 268 tumor samples. The different PitNET subtypes were identified according to their immunohistochemical profile. We quantified the gene expression of POMC, AVPR1B, CRHR1, GH1, PRL, TSH, FSH and LHB by quantitative real-time-PCR (qRT-PCR). The data were expressed as mean and standard deviation (SD) of the Fold Change (FC). Qualitative variables were expressed as relative frequencies. T-Student, Mann-Whitney and Chi-squared tests were used to analyze the differences between functioning and silent tumors.

Results: 268 PitNETs (161 (60.1%) silent), were analyzed. Sixty percent of the patients were women, 95.5% were over the age of 25 (mean age and SD at diagnosis 49.74±15.37 years), 89.61% of the tumors were macroadenomas and 56.3% were invasive. Silent somatotropinomas and silent lactotropinomas showed lower expression of GH and PRL genes than their functioning variants (P<0.001 and P=0.023 respectively). Unusual silent plurihormonal PitNETs showed lower expression of POMC and AVPR1B (all P<0.05) and higher FSH expression than their functioning variant (P=0.001). Mixed silent somatotropinomas presented less expression of GH (P<0.001) but not of PRL genes (P=0.33) than mixed functioning ones. There were no statistically significant differences in the expression of POMC, AVPR1B and CRHR1 between functioning and silent corticotropinomas (all P>0.05). In the global series there were statistically significant differences between functioning and silent tumors according to gender, with a high frequency of men having silent tumors (P=0.007). The mean age was higher in silent than in functioning tumors (54.71 vs 42.25 years; P<0.001). Finally, silent PitNETs showed higher frequency of macroadenomas (P<0.001) and invasiveness (P<0.001) than functioning ones.

Conclusions: A lower expression of adenohypophyseal hormone genes could contribute to the silencing mechanisms of some subtypes of PitNETs. Silent tumors are bigger than functioning ones, more prevalent in men, and more invasive.