Reduced membranous MET expression is linked to bladder cancer progression.
The MET protein is involved in the malignant progression of different tumors. This study aimed to analyze the relationship of MET expression with tumor phenotype and clinical outcome in bladder cancer and the role of gene amplification for MET overexpression. A bladder cancer tissue microarray containing 686 bladder cancers was analyzed by immunohistochemistry and by fluorescence in situ hybridization. MET immunostaining was seen in normal urothelium and was recorded in 459 of 560 analyzable urothelial carcinomas (82.0%). Low MET staining was associated with a more unfavorable tumor phenotype. MET staining was seen in 89.8% of 266 pTa, 81.1% of 132 pT1, and 69.4% of 160 pT2-4 cancers (P < 0.0001). MET staining was detectable in 92.4% of 66 grade 1, 85.6% of 257 grade 2, and 75.1% of 237 grade 3 cancers (P = 0.001). MET expression status was not associated with overall or tumor-specific survival in muscle-invasive cancers (pT2-4), tumor progression in pT1 cancers, or recurrences in pTa tumors. Only four of the analyzed tumors (0.8%) showed amplification of the MET gene. We conclude that MET is not overexpressed in urothelial cancer but rather downregulated in a fraction of cancers. Accordingly, rare amplification of the genomic area including the MET gene was not associated with MET protein overexpression.
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Martina
M
Kluth
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Kristina
K
Reynolds
Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Michael
M
Rink
Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Felix
F
Chun
Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Roland
R
Dahlem
Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Margit
M
Fisch
Department of Urology, Clinical Center Itzehoe, Itzehoe, Germany.
Wolfgang
W
Höppner
Department of Urology, German Armed Forces Hospital, Hamburg, Germany.
Walter
W
Wagner
Department of Urology, Regio Clinic Wedel, Wedel, Germany.
Ousman
O
Doh
Institute of Pathology, University of Basel, Basel, Switzerland.
Luigi
L
Terracciano
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Ronald
R
Simon
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Guido
G
Sauter
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: s.minner@uke.de.
Sarah
S
Minner
D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D046888:Tissue Array Analysis; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D008565:Membrane Proteins; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
Bladder cancer; MET; immunohistochemistry; prognosis; tissue microarray