Oncogene-Induced Senescence in Pituitary Adenomas—an Immunohistochemical Study

Abstract

Oncogene-induced senescence (OIS) serves as an initial barrier to cancer development, being proposed as a possible explanation for the usually benign behavior of the pituitary adenomas. We aimed to explore the immunohistochemical expression of the OIS markers, senescence-associated lysosomal β-galactosidase (SA-β-GAL), p16, and p21 in different types of 345 pituitary adenomas and compared it with the expression in the normal pituitary and in the specimens from the repeated surgeries. SA-β-GAL was overexpressed in the pituitary adenomas, compared to the normal pituitaries. Growth hormone (GH) producing adenomas showed the strongest SA-β-GAL, with densely granulated (DG)-GH adenomas more reactive than the sparsely granulated (SG). Nuclear p21 was decreased in the adenomas, except for the SG-GH adenomas that had higher p21 than the normal pituitaries and the other adenomas. p16 was significantly lower in the adenomas, without type-related differences. SA-β-GAL was slightly lower and p16 slightly higher in the recurrences. Our findings indicate alterations of the senescence program in the different types of pituitary adenomas. Activation of senescence in the pituitary adenomas presents one possible explanation for their usually benign behavior, at least in the GH adenomas that show a synchronous increase of two OIS markers. However, subdivision into GH adenoma subtypes reveals differences that reflect complex regulatory mechanisms influenced by the interplay between the granularity pattern and the hormonal factors, with possible impact on the different clinical behavior of the SG- and DG-GH adenoma subtypes. p16 seems to have a more prominent role in the pituitary tumorigenesis than in the senescence. Recurrent growth in a subset of the pituitary adenomas is not associated with consistent changes in the senescence pattern.

Genome-wide analysis of differentially expressed lncRNAs and mRNAs in primary gonadotrophin adenomas by RNA-seq

“…Intriguingly, these reports are consistent with our finding and these pathways should be further investigated for their potential therapeutic value. Meanwhile, our results, together with those of previous studies, suggested that other processes such as oncogene-induced senescence attenuate the changes in the downstream of PI3K/Akt/mTOR pathway in these benign tumors [34, 35]. …”

Wszystko co świeci w PET nie jest nowotworem złośliwym! Wychwyt 18F-deoksyglukozy a biologia nowotworu: incidentaloma przysadki mózgowej u chorego, który przebył dwie niezwiązane choroby nowotworowe

“…OIS has been proposed as a possible explanation for the prevalently benign behaviour of pituitary adenomas. However, in this patient, a very low prevalence of p16 and p21 positive nuclei, did not support senescence as the explanation for tumour 's low proliferative activity, although it was in consonance with the hormonal activity [22,23]. Importantly, studies that compare the biology of pituitary adenomas and their radiological properties using magnetic resonance and PET/CT are still lacking.…”

Immediate ex-vivo diagnosis of pituitary adenomas using confocal reflectance microscopy: a proof-of-principle study

“…Indeed, the characterization of pituitary adenomas on the basis of genetic and molecular characteristics, and the link between these markers and clinical behavior, has grown exponentially within the past decade. 3,8,11,18 Given the recent advances in our knowledge in these fields, biopsy specimen preservation and biobanking for research studies are arguably more important now than at any time in the past.…”