Expression of cyclin kinase inhibitor p21/WAF1 protein in pituitary adenomas: correlations with endocrine activity,
1Department of Neurosurgery, Neurological Institute, Tokyo Women's Medical University, Japan.
Abstract:
p21/WAF1 blocks cell cycle progression through inhibition of cyclin/cyclin-dependent kinases (cdks) complexes and, simultaneously, has been associated with cell cycle exit and the process of differentiation. In this series, the expression of p21/WAF1 was assessed immunohistochemically in 47 cases of pituitary adenomas in relation to endocrine activity and cell proliferation. To evaluate cell proliferation, a monoclonal antibody, MIB-1, against Ki-67 antigen was used in all of the available cases. The study revealed positive p21/WAF1 staining in 24 cases of 26 functioning parenchymas, whereas 14 cases of 21 non-functioning parenchymas stained negative. The MIB-1 index ranged from less than 1% to 5.1% (mean: less than 1.7%) in functioning adenomas, and from less than 1% to 3.6% (mean: less than 1.6%) in non-functioning adenomas. Regardless of endocrine activity, p21/WAF1 positivity did not correlate with the MIB-1 index. Double staining techniques revealed the co-expression of p21/WAF1/GH or p21/WAF1/PRL in functioning adenomas. In 22 cases of p21/WAF1-positive functioning adenomas, p21/WAF1 immunoreactivity was seen in the cytoplasma as well as nuclei. These results indicate that in pituitary adenomas, p21/WAF1 expression is associated with endocrine activity, but not with cell proliferation. Taken together with recent findings demonstrating that cytoplasmic p21/WAF1 acts as an inhibitor of apoptosis, it is possible that pituitary adenomas expressing cytoplasmic p21/WAF1 have resistance against DNA-damaging agents such as ionizing radiation.
Insights
p21/WAF1 expression in pituitary adenomas correlates with endocrine activity, not cell proliferation. Cytoplasmic p21/WAF1 may confer resistance to DNA-damaging agents like radiation.
Area of Science:
- Endocrinology
- Oncology
- Cell Biology
Background:
- p21/WAF1 (also known as CDKN1A) is a key cell cycle inhibitor involved in cell cycle arrest and differentiation.
- Its role in pituitary adenomas, particularly concerning endocrine activity and proliferation, requires further elucidation.
Purpose of the Study:
- To investigate the expression of p21/WAF1 in pituitary adenomas.
- To correlate p21/WAF1 expression with endocrine activity and cell proliferation markers.
- To explore the potential implications of p21/WAF1 expression in treatment resistance.
Main Methods:
- Immunohistochemical assessment of p21/WAF1 expression in 47 pituitary adenoma cases.
- Evaluation of cell proliferation using the MIB-1 antibody (Ki-67 antigen).
- Double staining techniques to identify co-expression with pituitary hormones (GH, PRL).
Main Results:
- p21/WAF1 was positive in 24/26 functioning adenomas and negative in 14/21 non-functioning adenomas.
- No correlation was found between p21/WAF1 positivity and the MIB-1 proliferation index.
- Co-expression of p21/WAF1 with GH or PRL was observed in functioning adenomas.
Conclusions:
- p21/WAF1 expression in pituitary adenomas is linked to endocrine activity, not cell proliferation.
- Cytoplasmic p21/WAF1 may contribute to resistance against DNA-damaging agents, potentially impacting therapeutic strategies.
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