Reduced expression of plakoglobin correlates with adverse outcome in patients with neuroblastoma.
Plakoglobin and its homologue beta-catenin are cytoplasmic proteins that mediate adhesive functions by interacting with cadherin receptors and signaling activities by interacting with transcription factors. It has been suggested that plakoglobin can suppress tumorigenicity whereas beta-catenin can act as an oncogene. We investigated the correlation between the expression pattern of N-cadherin, beta-catenin, and plakoglobin and tumor behavior in primary tumors of 20 neuroblastoma patients of all stages and in 11 human neuroblastoma cell lines. N-cadherin and beta-catenin were detected in 9 of 11 and 11 of 11 cell lines, respectively, whereas plakoglobin was undetectable or severely reduced in 6 of 11 cell lines. Tumor cells from 16 of 20 patients expressed N-cadherin and 20 of 20 patients expressed beta-catenin at levels similar to those of normal ganglion cells. Plakoglobin was undetectable in 9 of 20 tumors. Plakoglobin deficiency in the primary tumors was significantly associated with adverse clinical outcome. Five of the patients with plakoglobin-negative tumors died whereas four patients are alive without evident disease. In contrast, all patients with plakoglobin-positive tumors are alive; 2 of 11 are alive with the disease and 9 of 11 are alive without evident disease. These results suggest that down-regulation of plakoglobin may be of prognostic value for neuroblastoma patients as predictor of poor outcome.
Amitay
R
R
Institute of Hematology, the Department of Pathology, and the Institute of Pediatric Oncology, Chaim Sheba Medical Center, Tel-Hashomer. Weizmann Institute of Science, Rehovot, Israel.
Nass
D
D
Meitar
D
D
Goldberg
I
I
Davidson
B
B
Trakhtenbrot
L
L
Brok-Simoni
F
F
Ben-Ze'ev
A
A
Rechavi
G
G
Kaufmann
Y
Y
D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000378:metabolism*; D051180:Desmoplakins; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051176:beta Catenin; D051185:gamma Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D015534:Trans-Activators; D051176:beta Catenin; D051185:gamma Catenin