Expression of the cell cycle regulatory proteins p34cdc2, p21waf1, and p53 in node negative invasive ductal breast carcinoma.
OBJECTIVE
To look for correlations between expression of cell cycle regulatory proteins p34(cdc2), p21(WAF1), and p53 in node negative invasive ductal breast carcinoma, or between these proteins and clinicopathological parameters, and to assess their prognostic value.


METHODS
Immunohistochemistry using formalin fixed, paraffin wax embedded sections from 94 breast carcinomas. Adjacent benign epithelial breast tissue was available in 74 cases. Median follow up was 72 months.


RESULTS
Nuclear and cytoplasmic p34(cdc2) expression was seen in 80 and 62 tumours, respectively; nuclear expression was seen in adjacent benign epithelium in 12 cases. p21(WAF1) and p53 were positive in 48 and 21 tumours, respectively. High expression of p34(cdc2) in neoplastic nuclei was associated with higher histological grade and p53 expression, but not with tumour size, steroid receptor status, patient age, menopausal status, recurrence, metastasis, disease free survival (DFS), or overall survival (OS). p34(cdc2) in tumour cytoplasm was associated with p34(cdc2) nuclear positivity, high tumour grade, and DFS in univariate but not multivariate analysis. In contrast, p34(cdc2) expression in benign tissue independently predicted DFS and OS in univariate and multivariate analysis. Expression of p53 was associated with high tumour grade and negative steroid receptors, but not with recurrence, metastasis, DFS, or OS. p21(WAF1) expression was not associated with the examined parameters.


CONCLUSIONS
p34(cdc2), p21(WAF1), and p53 expression does not predict outcome in node negative breast carcinoma, although p34(cdc2) expression in benign tissue is related to prognosis. The association between p34(cdc2) and p53 implicates p53 in G2-M cell cycle checkpoint control, possibly via mediators unrelated to p21(WAF1).
Kourea
H P
HP
Department of Pathology, University Hospital of Patras, Patras Medical School, Patras, Rion 26500, Greece. hkourea@yahoo.com
Koutras
A K
AK
Scopa
C D
CD
Marangos
M N
MN
Tzoracoeleftherakis
E
E
Koukouras
D
D
Kalofonos
H P
HP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry*; D016203:CDC2 Protein Kinase / Q000032:analysis; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry*; D018797:Cell Cycle Proteins / Q000032:analysis*; D016009:Chi-Square Distribution; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D016203:CDC2 Protein Kinase