Expression of p27kip1 in breast cancer and its prognostic significance.
p27kip1 is a member of the KIP/CIP family of cyclin-dependent kinase inhibitors and is a negative cell-cycle regulator that is thought to play a role in tumour suppression. Reduced levels of this protein have been observed in a number of human cancers. However, evidence is conflicting as to whether p27kip1 has a role to play in breast cancer, including predicting behaviour and prognosis. The present investigation aimed to provide a definitive study of 830 breast cancer cases with median patient follow-up of 104 months to determine the true prognostic significance, if any. Immunohistochemical analysis of tissue microarrays and three scoring methods were used to assess p27kip1 expression. Univariate analysis showed a significant relationship between reduced p27kip1 expression and increasing tumour grade, nuclear pleomorphism, mitosis, and decreasing tubule formation (all p<0.001). Significant associations between reduced p27, negative oestrogen receptor status, and ductal/no special type tumours were also observed. Survival analysis demonstrated that patients with tumours with high p27kip1 levels had an improved survival compared with those with cancers with low expression. On multivariate analysis, when compared with existing factors, p27kip1 was not, however, an independent prognostic factor. It is concluded that the inverse relationship between p27kip1 levels and histological grade and individual grade components suggests a role for p27kip1 in both cell proliferation and differentiation, but is not clinically useful.
Department of Histopathology, Nottingham City Hospital Breast Unit, Nottingham, UK.
A
A
Barnes
S E
SE
Pinder
J A
JA
Bell
E C
EC
Paish
P M
PM
Wencyk
J F R
JF
Robertson
C W
CW
Elston
I O
IO
Ellis
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D002452:Cell Count; D018797:Cell Cycle Proteins / Q000032:analysis*; D002467:Cell Nucleus / Q000473:pathology; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004273:DNA, Neoplasm / Q000032:analysis; D004791:Enzyme Inhibitors / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008875:Middle Aged; D008938:Mitosis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009363:Neoplasm Proteins / Q000032:analysis*; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis; D015203:Reproducibility of Results; D025521:Tumor Suppressor Proteins / Q000032:analysis*
D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27