Down-regulated expression of cytokeratin 18 promotes progression of human breast cancer.
OBJECTIVE
Cytokeratins (CKs) have been recognized for >20 years as structural marker proteins specific for epithelial cells. Recent expression profiling analyses indicate, however, that CK down-regulation may occur in breast cancer.


METHODS
Here we evaluated the expression pattern of CK18 by immunohistochemical analysis of primary breast carcinomas (n = 1458) spotted on a high-density tissue microarray. The findings were correlated to histopathological risk factors and clinical outcome.


RESULTS
Down-regulation of CK18 (as compared to normal breast tissue) was observed in 25.4% of the tumors with a lower rate in lobular carcinomas (17.0%) than in ductal carcinomas (25.4%) or other histological entities (32.5%). CK down-regulation was significantly correlated to advanced tumor stage and high grade but not to axillary lymph node status. Kaplan-Meier survival analysis revealed CK18 as a prognostic indicator of overall survival (P = 0.015) and cancer-specific survival (P = 0.005).


CONCLUSIONS
Down-regulation of the luminal CK18 is not rare and a clinically relevant event in breast cancer. This finding has important implications for the use of CK18 as epithelial tumor marker. The correlations with clinical follow-up suggest that CK18 might suppress tumor progression.
Woelfle
Ute
U
Institute of Tumor Biology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Sauter
Guido
G
Santjer
Sonja
S
Brakenhoff
Ruud
R
Pantel
Klaus
K
D000368:Aged; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism; D044584:Carcinoma, Ductal / Q000378:metabolism; D018275:Carcinoma, Lobular / Q000378:metabolism; D018450:Disease Progression; D015536:Down-Regulation; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000096:biosynthesis*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011379:Prognosis; D040081:Protein Array Analysis; D012307:Risk Factors; D013997:Time Factors
D014408:Biomarkers, Tumor; D007633:Keratins