Trop-2 overexpression as an independent marker for poor overall survival in ovarian carcinoma patients.
BACKGROUND
Prognostic factors currently available are insufficient to predict the clinical course of epithelial ovarian cancer (EOC). In a previous microarray study we identified the human trophoblast cell surface antigen Trop-2 as one of the top differentially expressed genes in serous papillary EOCs compared to normal human ovarian surface epithelial (HOSE) short-term cultures. The aim of the present investigation was to analyse Trop-2 expression at mRNA and protein level and to assess its prognostic significance in EOC.


METHODS
Using quantitative real-time PCR we tested a total of 104 fresh-frozen EOC tissues and 24 HOSE for Trop-2 mRNA expression. Trop-2 protein expression was then examined by immunohistochemistry in matched formalin-fixed paraffin-embedded EOC samples and in 13 normal ovaries. Finally, we correlated Trop-2 expression to EOC conventional clinicopathological features and patient outcomes.


RESULTS
We found a significant Trop-2 mRNA and protein upregulation in EOCs compared to normal controls (p<0.001). Trop-2 protein overexpression was significantly associated with the presence of ascites (p=0.04) and lymph node metastases (p=0.04). By univariate survival analysis, Trop-2 protein overexpression was significantly associated with decreased progression-free (p=0.02) and overall survival (p=0.01). Importantly, Trop-2 protein overexpression was an independent prognostic marker for shortened survival time in multivariate Cox regression analysis (p=0.04, HR=2.35, CI(95%)=1.03-5.34).


CONCLUSIONS
Our results indicate, for the first time, that Trop-2 protein overexpression correlates with an aggressive malignant phenotype and may constitute a novel prognostic factor for EOC. The targeting of Trop-2 overexpression by immunotherapeutic strategies may represent an attractive and potentially effective approach in patients harbouring EOC.
Bignotti
Eliana
E
Division of Gynecologic Oncology, University of Brescia, Viale Europa 11, 25123 Brescia, Italy. bignottieliana@yahoo.it
Todeschini
Paola
P
Calza
Stefano
S
Falchetti
Marcella
M
Ravanini
Maria
M
Tassi
Renata A
RA
Ravaggi
Antonella
A
Bandiera
Elisabetta
E
Romani
Chiara
C
Zanotti
Laura
L
Tognon
Germana
G
Odicino
Franco E
FE
Facchetti
Fabio
F
Pecorelli
Sergio
S
Santin
Alessandro D
AD
D000368:Aged; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D007558:Italy; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis*; D016019:Survival Analysis
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C499380:TACSTD2 protein, human