p21/WAF1/Cip1 expression in invasive ductal breast carcinoma: relationship to p53, proliferation rate, and survival at 5 years.
The p21/WAF1/Cipl antibody, DCS-60, was characterized by means of immunoblotting and immunofluorescence on a variety of human breast cancer cell lines. Heterogeneous staining of nuclei was observed with strong staining of cells in early G1. p21/WAF1/Cipl expression in invasive ductal, not otherwise specified breast carcinomas was determined using immunohistochemistry with this antibody and computerized image analysis. Two hundred and twenty-two tumors, including 130 from patients with no axillary node involvement, were examined. p21-positive tumor cell nuclei were found in 30% of the breast carcinomas. The percentage of tumor cell nuclei that were positive ranged from less than 1% to greater than 10%. In the whole cohort of patients, p21 expression was significantly associated with a low histological grade. In the node-negative group, there was a significant negative correlation between p21 positivity and a high (>10%) MIB-1 score. The mean MIB-1 score was significantly lower in p21-positive tumors in the whole cohort of patients (P=0.03) and in the nodenegative group (P=0.02). No association was found between p21 expression and overall survival at 5 years. With respect to p21/p53 phenotype, the significant difference in survival was noted only for the group of patients treated with adjuvant chemotherapy. The p21- p53+ phenotype had the worst survival (58% surviving 5 years), while the p21+ p53- phenotype had good survival (83% surviving 5 years; P<0.05). The results seem to suggest a correlation between p21/p53 phenotype and response to adjuvant chemotherapy.
Domagala
W
W
Department of Pathology, Faculty of Medicine, Pomeranian Medical Academy, Szczecin, Poland.
Welcker
M
M
Chosia
M
M
Karbowniczek
M
M
Harezga
B
B
Bartkova
J
J
Bartek
J
J
Osborn
M
M
D000911:Antibodies, Monoclonal; D034961:Antigens, Nuclear; D015415:Biomarkers / Q000032:analysis; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D002455:Cell Division; D017024:Chemotherapy, Adjuvant; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000276:immunology / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D009687:Nuclear Proteins / Q000378:metabolism; D015996:Survival Rate; D014407:Tumor Cells, Cultured / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D034961:Antigens, Nuclear; D015415:Biomarkers; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53