Endocrine Abstracts

Background/Aim: Pituitary neuroendocrine tumors (PitNETs), although usually indolent, may display aggressive behavior. YAP/TAZ signalling has been linked to pituitary development and stem cell regulation, with a preliminary study from our group revealing elevated levels and nuclear localization of YAP/TAZ in non-functioning PitNETs (NF-PitNETs). CTGF, a YAP/TAZ target gene, encodes a secreted factor involved in proliferation and angiogenesis, that has been implicated in tumor development. We aim to use specimens of human PitNETs to assess the expression of CTGF and correlate with clinical and pathology data.

Material and methods: The clinical and pathology data of 13 patients with PitNETs were initially investigated, including seven patients with functioning and six patients with NF-PitNETs. Their clinical characteristics were analyzed, including age, tumor size, and outcome (remission, recurrence, progression). The 5th edition of WHO classification was used. The expression of CTGF in pituitary tumor sections was assessed using RNAscope mRNA in situ hybridization (ACDBioTechne). CTGF expression was subdivided into four groups based on a semiquantitative scoring system (Very low 0, Low 1, Medium 2, High 3). The tumor subtype, Ki-67 proliferation index, and the MGMT presence (>50%) were correlated with the clinical data and tumor behavior. This study was approved by the Institutional Review Board and all patients provided informed consent.

Results: Our preliminary results showed that CTGF is expressed statistically higher (Score 2-3) in patients with Ki-67 above 7% (P<0.05). Among six patients with NF-PitNETs, one patient had medium, and three had high levels of CTGF (16,6% and 50%, respectively), correlated with Ki-67 above 7% and a recurrence/progression rate of 100%. Interestingly, there was high expression of CTGF (Score 3) in two patients with immature POU1F1-lineage PitNETs, which lack terminal differentiation. In patients with functioning PitNETs, 3 out of 7 cases were characterized by medium levels of CTGF (Score 2) and were correlated with younger age (<40 years), with high Ki-67 levels above 10% and with MGMT presence (2 out of 3 cases, 66%). None of the remaining four functioning PitNETs with CTGF Score 0-1 and low Ki-67 <3% recurred.

Conclusion: Our preliminary data show increased expression of CTGF in NF-PitNETs, particularly in immature subtypes, with high levels of Ki-67 and in functioning PitNETs presenting in younger patients with high Ki-67 and MGMT expression. All patients with high expression of CTGF recurred/progressed. Our findings suggest that YAP/TAZ signalling may have a critical role in PitNETs with more aggressive behavior.