Overexpression of cyclo-oxygenase-2 is an independent predictor of unfavourable outcome in node-negative breast cancer, but is not associated with protein kinase B (Akt) and mitogen-activated protein kinase (ERK1/2, p38) activation or with Her-2/neu signalling pathways.
OBJECTIVE
The production of prostaglandins is regulated by cyclo-oxygenases (COXs), which also have a role in tumour development and progression in various malignancies, including breast cancer. The mechanisms by which COX-2 contributes to unfavourable prognosis are still poorly understood. The association between expression of COX-2 and possible linked signalling pathways-namely, Akt, extracellular regulated kinases (ERK1/2), the stress-activated kinase p38 or Her-2/neu-is assessed in a series of 113 node-negative breast cancers.


RESULTS
COX-2 was identified as an independent prognostic factor (p = 0.034) in node-negative breast cancer by survival analysis. The lack of a relationship between COX-2 expression and activated Akt, Erk1/2, p38 and Her-2/neu was indicated by statistical analysis.


CONCLUSIONS
The prognostic effect of COX-2 expression on lymph node-negative breast cancer is confirmed-COX-2 is probably not regulated by HER-2, Akt, Erk1/2 or p38. Further studies are necessary for the elucidation of the signalling pathways responsible for the modification of COX-2 expression and the increased aggressiveness of breast cancers overexpressing COX-2.
Institute of Pathology, University Hospital of Essen, Germany.
K J
KJ
Schmitz
R
R
Callies
J
J
Wohlschlaeger
R
R
Kimmig
F
F
Otterbach
J
J
Bohr
H-S
HS
Lee
A
A
Takeda
K W
KW
Schmid
H A
HA
Baba
D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D016019:Survival Analysis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D014408:Biomarkers, Tumor; D051546:Cyclooxygenase 2; D009363:Neoplasm Proteins; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D048051:p38 Mitogen-Activated Protein Kinases