Reduced nuclear expression of transcription factor AP-2 associates with aggressive breast cancer.
OBJECTIVE
We proposed to investigate the expression and prognostic significance of activator protein 2 (AP-2) in breast cancer.


METHODS
AP-2 was immunohistochemically analyzed in a prospective, consecutive series of 420 breast cancer patients diagnosed and treated between 1990 and 1995 at Kuopio University Hospital, Kuopio, Finland. AP-2 expression was further compared with clinicopathological parameters and patients' survival.


RESULTS
Nuclear AP-2 expression was lower in carcinomas compared with normal ductal breast epithelium (P < 0.001). Nuclear expression was more often seen in lobular than in ductal or other carcinomas (P = 0.048). Cytoplasmic staining was present in 47% of the carcinomas. Low nuclear AP-2 expression level in carcinomas was associated with advanced stage (P = 0.002), axillary lymph node positivity (P = 0.012), poor differentiation (P = 0.001), and recurrences (P = 0.003). In univariate survival analyses, low nuclear AP-2 expression (P = 0.0028), advanced stage (P < 0.0001), lymph node metastases (P < 0.0001), and poor differentiation (P = 0.0498) predicted shorter recurrence-free survival (RFS). Low nuclear AP-2 staining and/or shift to cytoplasmic expression predicted shorter RFS (P = 0.0050) and breast cancer-related survival (BCRS; P = 0.0314) in univariate analyses. Cytoplasmic expression alone did not have prognostic value. In multivariate analysis, low nuclear AP-2 expression (P = 0.0292) and advanced stage (P = 0.0001) were independent predictors of shorter RFS; and stage (P < 0.0001) and ER-status (P = 0.0321) independently predicted BCRS. In the lymph-node positive patients, RFS was independently predicted by stage (P = 0.0110) and nuclear AP-2 status (P = 0.0151).


CONCLUSIONS
AP-2 seems to have a protective role in breast cancer. Low nuclear AP-2 expression was associated with disease progression and increased metastatic capability of the tumor. In addition, reduced nuclear AP-2 expression independently predicted elevated risk of recurrent disease in breast cancer.
Pellikainen
Johanna
J
Department of Pathology and Forensic Medicine, University of Kuopio, FIN-70211 Kuopio, Finland.
Kataja
Vesa
V
Ropponen
Kirsi
K
Kellokoski
Jari
J
Pietiläinen
Timo
T
Böhm
Jan
J
Eskelinen
Matti
M
Kosma
Veli-Matti
VM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D016016:Proportional Hazards Models; D013997:Time Factors; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000096:biosynthesis*
D004268:DNA-Binding Proteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors