Korean J Pathol.  2009 Feb;43(1):56-62. 10.4132/KoreanJPathol.2009.43.1.56.

Functional Inactivation of pRb Associated with Cyclin D1- and Cyclin-dependent Kinase 4 Overexpression Plays A Key Role in Human Pituitary Tumorigenesis

• Myong NH

• KMID: 1472555
• DOI: http://doi.org/10.4132/KoreanJPathol.2009.43.1.56

Abstract

BACKGROUND: Human pituitary adenoma (PA) is a common intracranial tumor, but the mechanism underlying tumorigenesis has not been established. Functional inactivation of retinoblastoma protein (pRb) following cyclin D1- and cyclin-dependent kinase (CDK) 4-dependent hyperphosphorylation is one of the most important mechanisms in tumor cell proliferation. We evaluated immunohistochemical expressions of cyclin D1, CDK4 and phosphorylated pRb (p-pRb) in 50 PAs to investigate a role for functional inactivation of pRb associated with cyclin D1/CDK4 overexpression in pituitary tumorigenesis and to correlate it with clinicopathologic variables.
METHODS
Fifty human PAs were immunohistochemically stained for cyclin D1, CDK4 and p-pRb (Thr 356). Correlations between their expression and the clinicopathologic characteristics were statistically analyzed.
RESULTS
Cyclin D1 and CDK4 were overexpressed in 56% and 64%, respectively; pRb was hyperphosphorylated in 64%. Forty one cases (82%) showed one or more of these altered expressions. Overexpressions of cyclin D1 and CDK4 were correlated with functional pRb inactivation. Cyclin D1 overexpression was associated with apoplexy and growth hormone production.
CONCLUSIONS
Functional inactivation of pRb associated with the cyclin D1/CDK4 overexpression might play a key role in human pituitary tumorigenesis. CDK4 worked in concert with cyclin D1 to hyperphosphorylate pRb. Pituitary apoplexy appeared to be associated with cyclin D1 overexpression.

Keyword

Pituitary adenoma; Retinoblastoma protein; Cyclin D1; Cyclin-dependent kinase 4; Immunohistochemistry

MeSH Terms

Cell Proliferation
Cell Transformation, Neoplastic
Cyclin D1
Cyclin-Dependent Kinase 4
Cyclins
Growth Hormone
Humans
Immunohistochemistry
Phosphotransferases
Pituitary Apoplexy
Pituitary Neoplasms
Retinoblastoma Protein
Stroke
Cyclin D1
Cyclin-Dependent Kinase 4
Cyclins
Growth Hormone
Phosphotransferases
Retinoblastoma Protein