Immunohistochemical Expression of p16 and p21 in Pituitary Tissue Adjacent to Pituitary Adenoma versus Pituitary Tissue Obtained at Autopsy: Is There a Difference?

Abstract

Normal pituitary tissue is frequently used for comparison with protein expression in tumor tissue, being obtained either at surgery or at autopsy. p16 and p21 proteins are cyclin-dependent kinase inhibitors, belonging to INK4 and Cip/Kip family, respectively. Their expression is increased in response to DNA damage or other cellular stressors, resulting in the activation of cell cycle checkpoints. They also play important roles in cellular senescence. The purpose of this study was to investigate differences in p16 and p21 immunohistochemical expression in normal pituitary tissue adjacent to pituitary adenoma obtained during neurosurgical procedure with pituitary tissue obtained at autopsy, from patients who died from non-endocrinological diseases. Our results show significant difference in p16 nuclear and p21 cytoplasmic immunohistochemical expression between two types of normal pituitary tissues. One of the reasons for this difference could be the age of subjects because those who underwent autopsy for a non-endocrinological disease were significantly older than subjects who underwent neurosurgery for a pituitary adenoma. Our finding that differences are probably not influenced by postmortem changes is supported by no significant correlation between postmortem interval and immunohistochemical p16 and p21 expression. The influence of the presence of a pituitary adenoma could not be evaluated in these specimens.

Ultrastructural and Molecular Evidence of Macroautophagy in Functioning PitNETs and Experimental Pituitary Tumors

“…The normal pituitary gland also exhibited between 5% and 8% immunopositive cells for these proteins in adenoparenchyma. However, it is well known that postmortem autolytic changes in the tissue affect many proteins [34]. In the PitNETs, the percentage of immunoreactive cells in each sample varied between 11% and 50%.…”

Architects of Pituitary Tumour Growth

“…Significant differences in CS marker expression have been detected in human PitNETs ( 139 – 141 ). Moreover, a certain specificity of this cellular phenomenon to the tumour subtype has been suggested, as frequently aggressive ACTH tumours present lower senescence signs ( 141 ).…”

“…Significant differences in CS marker expression have been detected in human PitNETs ( 139 – 141 ). Moreover, a certain specificity of this cellular phenomenon to the tumour subtype has been suggested, as frequently aggressive ACTH tumours present lower senescence signs ( 141 ). Several experimental models have reported the contribution of CS during pituitary tumorigenesis ( 112 – 114 , 142 – 144 ), supporting the idea it may be an impediment against oncogenic stimulation and prevent cellular transformation ( 145 ).…”

“…Yet, its deletion or overexpression promotes pituitary p53/p21-dependent senescence in GH-secreting cells ( 22 , 112 , 114 , 147 ). Furthermore, the involvement of tissue-specific pathways has been proposed of intra-nuclear p21Cip1 diverse expression, p16Ink4a and p15Ink4b ( 112 , 114 , 139 – 141 ).…”