Expression of the cell-cycle regulatory proteins (pRb, cyclin D1, p16INK4A and cdk4) in human endometrial cancer: correlation with clinicopathological features.
BACKGROUND
Derailments of the control mechanisms in the G1/S phase of the cell cycle play a fundamental role in the initiation and progression of cancer. However, only a few reports have addressed the issue of simultaneously occurring abnormalities of Rb-pathway components in malignant endometrial tumors.


METHODS
Currently, we assessed the expression of cell-cycle regulatory proteins (pRb, cyclin D1, p16(INK4A) and cdk4) in 48 sporadic endometrial cancers, and investigated these tumors for a possible relationship between aberrant protein staining and clinicopathological variables of cancer and RB-LOH.


RESULTS
There was abnormal pRb, cyclin D1, p16(INK4A) and cdk4 immunoreactivity in 2%, 50%, 6% and 25% of cases, respectively. Altogether, 33 of 48 (69%) endometrial malignant tumors showed abnormal expression of at least one Rb-pathway protein immunohistochemically. However, there was significant correlation neither between the cell-cycle regulators nor between the frequency of pRb, p16(INK4A) and cyclin D1 abnormalities and clinicopathological variables of cancer, but a significant correlation did exist between cdk4 staining and the clinical stage of disease ( P<0.05, Fisher's exact test). Moreover, an inverse relationship was also demonstrated between cdk4 expression and patient age ( r=-0.367; P=0.01). However, none of the cell-cycle regulatory proteins, except for pRb, was related to loss of heterozygosity at locus 13q14.


CONCLUSIONS
As a conclusion, derailments of the Rb-pathway components, cyclin D1 and cdk4 in particular, seems to participate in the endometrial cancer development in humans. Overexpression of cdk4 was related to the progression of neoplastic disease and corresponds with age of onset, suggesting a major role of altered cdk4 immunoreactivity in the progression of endometrial cancer.
Semczuk
Andrzej
A
2nd Department of Gynecology, University School of Medicine, 8 Jaczewski Street, 20-954, Lublin, Poland. tomek@asklepios.am.lublin.pl
Miturski
Roman
R
Skomra
Danuta
D
Jakowicki
Jerzy A
JA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics; D051358:Cyclin-Dependent Kinase 4; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008875:Middle Aged; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein / Q000235:genetics
D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D019938:Cyclin D1; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases