Epithelial cell adhesion molecule (KSA) expression: pathobiology and its role as an independent predictor of survival in renal cell carcinoma.
OBJECTIVE
Epithelial cell adhesion molecule (EpCAM) is a widely expressed adhesion molecule in epithelial cancers. The purpose of this study is to determine the protein expression patterns of EpCAM in renal cell carcinoma (RCC) using tissue arrays linked to a clinicopathological database to evaluate both its predictive power in patient stratification and its suitability as a potential target for immunotherapeutic treatment strategies.


METHODS
The University of California, Los Angeles kidney cancer tissue microarray contains specimens from 417 patients treated with nephrectomy. EpCAM protein expression in tumors and matched morphologically normal renal tissues was evaluated using anti-EpCAM immunohistochemistry. The resultant expression reactivity was correlated with clinicopathological variables.


RESULTS
EpCAM is consistently expressed in the distal nephron on normal renal epithelium. Clear cell RCCs show minimal and infrequent EpCAM expression, whereas chromophobe and collecting duct RCCs both demonstrate intense and frequent expression. Of 318 clear cell carcinomas used in the analysis, 10% were EpCAM positive in > or = 50% of cells, and 8% of patients would be considered candidates for EpCAM-based therapy, based on high expression [> or = moderate intensity and frequent (> or = 50%) expression] and the need for systemic treatment. EpCAM expression was an independent prognostic factor for improved disease-specific survival, with a multivariate hazard ratio of 0.63 (P = 0.017; 95% confidence interval, 0.43-0.92).


CONCLUSIONS
EpCAM is a novel prognostic molecular marker in RCC patients, and its positive expression is an independent predictor associated with improved survival. However, high expression in morphologically normal renal tissues and minimal or absent expression in clear cell carcinomas will likely limit the utility of this epithelial marker in targeted treatments of this most common RCC type.
Seligson
David B
DB
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine University of California Los Angeles, Los Angeles, California 90095, USA.
Pantuck
Allan J
AJ
Liu
Xueli
X
Huang
Yunda
Y
Horvath
Steven
S
Bui
Matthew H T
MH
Han
Ken-ryu
KR
Correa
Adrian J L
AJ
Eeva
Mervi
M
Tze
Sheila
S
Belldegrun
Arie S
AS
Figlin
Robert A
RA
D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000502:physiology*; D014408:Biomarkers, Tumor; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000401:mortality*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000502:physiology*; D018572:Disease-Free Survival; D000071858:Epithelial Cell Adhesion Molecule; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism; D011379:Prognosis; D016016:Proportional Hazards Models; D040081:Protein Array Analysis; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule