The p21(WAF1/Cip1) (p21) protein, a negative regulator of G(1) checkpo
int control, was overexpressed in the majority of human gliomas. To in
vestigate whether p21 expression in brain metastases from various syst
emic origins is similar to that in gliomas and whether p21 expression
is regulated differently in brain metastases and in corresponding prim
ary tumors, we used immunohistochemical staining to examine the expres
sion of p21 in paraffin-embedded sections prepared from primary colon
and breast carcinomas and from metastatic brain tumors that originated
from colon, breast, lung, and kidney cancers and from melanoma. Our r
esults showed that 56% (28 of 50) of the brain metastases samples have
more than 1% p21-positive staining cells compared with 87% of primary
gliomas reported previously. Among the samples analyzed, p21 expressi
on in brain metastases from breast carcinomas was much higher than in
primary breast carcinomas. In contrast, p21 expression in brain metast
ases from colon carcinomas was less than primary colon carcinomas. The
results from this pilot study suggest that p21 expression is regulate
d differently in metastatic and primary tumors.