Article

Altered expression of G1 regulatory proteins in human soft tissue sarcomas.

Department of Pathology, St Vincent's Hospital, Catholic University, South Korea.
Archives of pathology & laboratory medicine (impact factor: 2.58). 06/2002; 126(5):567-73. DOI:10.1043/0003-9985(2002)126<0567:AEOGRP>2.0.CO;2
Source: PubMed

ABSTRACT Soft tissue sarcomas constitute a heterogeneous group of tumors for which tumorigenesis is not fully understood. Altered cell-cycle regulation may underlie the development and/or progression of human malignancies. However, data concerning the occurrence of cell-cycle aberrations in soft tissue sarcomas are very limited.
To detect the abnormal features of cell-cycle regulatory proteins in soft tissue sarcomas and to determine the potential role of these proteins in clinical behavior.
The p53 and Rb-cyclin D pathways were investigated by immunohistochemical studies of p53, mdm2, pRb, p16, cyclin D1, and cdk4 proteins, respectively.
Of the 67 sarcomas analyzed, nuclear accumulation of p53 was detected in 25 samples (37%), and overexpression of mdm2 was found in 16 samples (24%). Both p53 and mdm2 expression correlated with tumor grade. Abnormalities involving the Rb-cyclin D pathway were identified in all of the tumors by the altered expression of either pRb (72%) or p16 (94%). Fourteen (21%) and 64 (96%) cases demonstrated cyclin D1 or cdk4 expression, respectively. Overexpression of cyclin D1 showed an association with pRb and p53. There was no correlation between pRb, p16, cyclin D1, or cdk4 and tumor grade or relapse.
Disturbance in the cell-cycle regulatory system involving the p53 pathway and the Rb-cyclin D pathway is relatively frequent in soft tissue sarcomas and may be a contributing factor in the tumorigenesis of these tumors. The alterations in the Rb-cyclin D pathway probably constitute an early event, whereas the abnormalities in the p53 pathway seem to be involved in tumor progression. It is noteworthy that cyclin D1 may play a key role in linking both pathways.

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Keywords

16 samples
 
67 sarcomas analyzed
 
abnormal features
 
Altered cell-cycle regulation
 
altered expression
 
cell-cycle aberrations
 
cell-cycle regulatory proteins
 
cell-cycle regulatory system
 
contributing factor
 
cyclin D1
 
heterogeneous group
 
mdm2 expression correlated
 
nuclear accumulation
 
potential role
 
Rb-cyclin D pathway
 
Rb-cyclin D pathways
 
soft tissue sarcomas
 
tumor grade
 
tumor progression
 
tumors
 

Jinyoung Yoo