Cytoplasmic Trop-1/Ep-CAM overexpression is associated with a favorable outcome in node-positive breast cancer.
OBJECTIVE
Trop-1/Ep-CAM modulates growth and survival of transformed cells, and it is highly expressed in most carcinomas including breast cancer. Only membranous staining is typically considered in evaluating Trop-1/epithelial cell adhesion molecule (Ep-CAM) expression in tumor cells. However, there is evidence of retention of Trop-1/Ep-CAM, as functionally incompetent molecules, in intra-cytoplasmic vesicles. Hence, we investigated whether cytoplasmic immunostaining may have an independent clinical significance with respect to membranous staining.


METHODS
Membranous and cytoplasmic Trop-1/Ep-CAM expression was immunohistochemically investigated in 642 unilateral breast cancers from patients with a 99-month median follow-up. Multiple correspondence analysis was used to investigate the association between Trop-1/Ep-CAM and other biological variables. The impact of Trop-1/Ep-CAM expression on the patient's outcome was evaluated as event-free survival by the Kaplan-Meier method and proportional hazard Cox model.


RESULTS
While tumors with intermediate/strong membranous staining were mostly associated with concomitant cytoplasmic Trop-1/Ep-CAM expression (97%), tumors with weak-to-nil membranous staining showed intermediate/high cytoplasmic expression in 23% of cases. Cytoplasmic overexpression was associated with a favorable outcome, especially in node-positive patients, regardless of the adjuvant therapy received.


CONCLUSIONS
Trop-1/Ep-CAM expression may have different clinical implications according to its subcellular localization.
Department of Clinical and Community Health Sciences, Medical Statistics, Biometry and Bioinformatics, University of Milan, Via Vanzetti 5, 20133 Milan, Italy.
Saverio
S
Alberti
Federico
F
Ambrogi
Patrizia
P
Boracchi
Marco
M
Fornili
Patrizia
P
Querzoli
Massimo
M
Pedriali
Rossana
R
La Sorda
Rossano
R
Lattanzio
Romina
R
Tripaldi
Mauro
M
Piantelli
Elia
E
Biganzoli
Danila
D
Coradini
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D018572:Disease-Free Survival; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007558:Italy / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D046888:Tissue Array Analysis
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule