M. Sanchezbeato et al., CYCLIN-DEPENDENT KINASE INHIBITOR P27(KIP1) IN LYMPHOID-TISSUE - P27(KIP1) EXPRESSION IS INVERSELY PROPORTIONAL TO THE PROLIFERATIVE INDEX, The American journal of pathology, 151(1), 1997, pp. 151-160
Cell cycle progression is regulated by the combined action of cyclins,
cyclin-dependent kinases (CDKs), and CDK inhibitors (CDKIs). p27(KIP1
), which has a high degree of similarity with p21(WAF1), is a general
CDK1 thought to be involved in G1 arrest in response to agents that in
hibit cell cycle progression. The aims of this study were 1) to establ
ish the pattern of expression of p27(KIP1) protein in nontumor lymphoi
d tissue, 2) to determine whether p27(KIP1) is involved in lymphomagen
esis, and 3) to address the possible relationship between p27(KIP1) an
d p21(WAF1) expression in reactive and tumor lymphoid tissue. p27(KIP1
) protein was found to be mainly present in quiescent lymphocytes in r
eactive lymphoid tissue as well as in peripheral blood lymphocytes, wi
th an inverse expression for p27(KIP1) and Ki-67 proteins. The same p2
7(KIP1) expression pattern was observed in lymphomas, independently of
histological type; small resting cells were p27(KIP1) positive, and l
arge proliferating cells were p27(KIP1) negative. Therefore, tumors wi
th a low proliferative index were mostly positive, whereas tumors char
acterized by a higher growth fraction had low p27(KIP1) protein levels
. An unexpected finding was the existence of a group of six cases of h
igh-grade lymphomas (three diffuse large B-cell lymphomas and three Bu
rkitt's lymphomas) with homogeneously strong staining for p27(KIP1) pr
otein. All 6 of these cases belong to a group of 28 cases characterize
d by blockage of the p53 tumor suppressor pathway, as determined by ge
netic (p53 mutation) or immunophenotypic studies (p53(+)/p21(-)). p27(
KIP1) expression was not seen in any case of aggressive non-Hodgkin's
lymphoma with an intact p53 pathway. The results indicate that p27(KIP
1) is down-regulated in lymphomas with a high proliferative index, alt
hough it is highly expressed in high-grade lymphomas with defects in t
he p53 pathway.