ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 P712 | DOI: 10.1530/endoabs.63.P712

Does silent pituitary neuroendocrine tumors show lower specific adenohypophyseal gene hormone expression than functioning ones?

María Eugenia Torregrosa1, Araceli García-Martínez2, Beatriz López-Muñoz3, Ángel Sánchez-Barbie4, Rosa Cámara5, Cristina Lamas6, Carmen Fajardo7, Sol Serrano3 & Antonio Picó8

1Clinical Analysis Department, Hospital General Universitario de Alicante, Alicante, Spain; 2Research Laboratory, Hospital General Universitario de Alicante-ISABIAL, Alicante, Spain; 3Endocrinology Department, Hospital General Universitario de Alicante, Alicante, Spain; 4Centro de Investigación Operacional, Universidad Miguel Hernández, Elche, Spain; 5Endocrinology Department, Hospital Universitario y Politécnico La fe, Valencia, Spain; 6Endocrinology Department, Complejo Hospitalario Universitario de Albacete, Albacete, Spain; 7Endocrinology Department, Hospital La Ribera, Alzira, Spain; 8Endocrinology Department, Hospital General Universitario de Alicante-ISABIAL, Alicante, Spain.

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.