We previously demonstrated that approximately one-half of soft-tissue sarco
mas were devoid of either pRB. the product of the retinoblastoma gene, or 1
6, the product of the MTS1/CDKN2 gene, while a smaller subset of aggressive
mesenchymal tumors without metastatic potential did not express RE by immu
nohistochemistry. We now studied the expression of two additional important
cell-cycle regulators, namely cyclin D1 and p53. in the same cohort of hig
h- and low-grade lesions. In the aggregate, our data provide a comprehensiv
e overview of the importance of cell-cycle deregulation in mesenchymal neop
lasia. Paraffin sections of 58 sarcomas and 23 soft-tissue tumors of low ma
lignant potential (STT-LMP) were reacted with monoclonal antibodies against
cyclin D1 and p53, using optimized immunohistochemical staining protocols.
The staining data were correlated with expression of pRB and p15 and with
a variety of pathologic parameters. A total of 33 of 58 sarcomas (57%) and
9 of 23 STT-LMP (39%) overexpressed p53. Fourteen sarcomas (24%) and 4 STT-
LMP (17%) overexpressed cyclin D1. There was no correlation between express
ion of these two genes and histologic tumor type or grade. Loss of RE and l
oss of p16 or overexpression of cyclin D1 were mutually exclusive events. C
onsidering all four cell-cycle regulators, sarcomas had a significantly hig
her abnormality rate than did STT-LMP (P < .005). Only 10% of the sarcomas
but 39% of STT-LMP showed normal expression of all four gene products. Base
d on our findings, overexpression of cyclin D1 and (presumably mutant) p53
appear to be among the most common molecular alterations in human mesenchym
al neoplasia. and abrogation of cell-cycle control is observed in the great
majority of sarcomas; it is present significantly less frequently in low-g
rade lesions.