Aggressive nonfunctioning pituitary neuroendocrine tumors.

Nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs) are tumors that are not associated with clinical evidence of hormonal hypersecretion. According to the World Health Organization (WHO), there are some subtypes of PitNETs that exhibit more aggressive behavior than others. Among the types of potentially aggressive PitNETs, three are nonfunctional: silent sparsely granulated somatotropinomas, silent corticotropinomas, and poorly differentiated PIT-1 lineage tumors. Several biological markers have been investigated in NF-PitNETs. However, there is no single biomarker able to independently predict aggressive behavior in NF-PitNETs. Thus, a more complex and multidisciplinary proposal of a comprehensive definition of aggressive NF-PitNETs is necessary. Here, we suggest a combined and more complete criterion for the NF-PitNETs classification. We propose that aggressiveness is due to a multifactorial combination, and we emphasize the need to include new emerging markers that are involved in the aggressiveness of NF-PitNETs and the need to identify.

Differential Expression of HMGA1 and HMGA2 in pituitary neuroendocrine tumors.

Defining biomarkers for invasive pituitary neuroendocrine tumors (PitNETs) is highly desirable. The high mobility group A (HMGA) proteins are among the most widely expressed cancer-associated proteins. Indeed, their overexpression is a frequent feature of human malignancies, including PitNETs. We show that nonfunctioning PitNETs (NF-PitNETs) express significantly higher levels of HMGA1 than somatotropinomas (GHs) and corticotropinomas (ACTHs). Furthermore, HMGA2 expression was detected only in NF-PitNETs and was significantly higher in larger tumors than in smaller tumors. HMGA expression analysis generally focuses on nuclear staining. Here, cytoplasmic HMGA staining was also found. PitNETs displayed strong nuclear HMGA1 and strong cytoplasmic HMGA2 immunoreactivity. Interestingly, the HMGA1 and HMGA2 nuclear expression levels were significantly higher in invasive adenomas than in noninvasive adenomas. The highest levels of nuclear HMGA2 were found in GHs. In conclusion, we show that overexpression of nuclear HMGA proteins could be a potential biomarker of invasive PitNETs, particularly HMGA2 for GHs. HMGA2 might be a reliable biomarker for NF-PitNETs.