High frequency of tumor cells with nuclear Egr-1 protein expression in human bladder cancer is associated with disease progression.
BACKGROUND
Egr-1 (early growth response-1 transcription factor) has been proposed to be involved in invasion and metastasis processes of human bladder cancer, but Egr-1 protein expression levels in human bladder cancer have not been investigated. In the present study we investigated the expression levels of Egr-1 protein in early stages of human bladder cancer and correlated it to later progression.


METHODS
Expression of Egr-1 protein in human bladder cancer was examined by immunohistochemistry, on a tissue microarray constructed from tumors from 289 patients with non-muscle invasive urothelial bladder cancer.


RESULTS
The frequency of tumor cells with nuclear Egr-1 immunolabelling correlated to bladder cancer stage, grade and to later progression to muscle-invasive bladder cancer (T2-4). Stage T1 tumors exhibited significantly higher frequencies of tumor cells with nuclear Egr-1 immunolabelling than Ta tumors (P = 0.001). Furthermore, Kaplan-Meier survival analysis showed that a high frequency of tumor cells with nuclear Egr-1 immunolabelling was significantly associated with a higher risk of progression to stage T2-4 (log-rank test, P = 0.035). Tumor cells with nuclear Egr-1 immunolabelling were found to localize at the tumor front in some of the tumor biopsies.


CONCLUSIONS
The results from this study support a potential involvement of Egr-1 in the progression from non-muscle invasive bladder cancers to muscle invasive bladder cancer.
Egerod
Frederikke Lihme
FL
Cell and Antibody Analysis, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Maaloev, Denmark. fle@life.ku.dk
Bartels
Annette
A
Fristrup
Niels
N
Borre
Michael
M
Ørntoft
Torben F
TF
Oleksiewicz
Martin B
MB
Brünner
Nils
N
Dyrskjøt
Lars
L
D018450:Disease Progression; D051766:Early Growth Response Protein 1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
D051766:Early Growth Response Protein 1