title: Trop-2 overexpression as an independent marker for poor overall survival in ovarian carcinoma patients.
abstract: 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.
authors.affiliation: Division of Gynecologic Oncology, University of Brescia, Viale Europa 11, 25123 Brescia, Italy. bignottieliana@yahoo.it
authors.forename: Eliana
authors.initials: E
authors.lastname: Bignotti
authors.forename: Paola
authors.initials: P
authors.lastname: Todeschini
authors.forename: Stefano
authors.initials: S
authors.lastname: Calza
authors.forename: Marcella
authors.initials: M
authors.lastname: Falchetti
authors.forename: Maria
authors.initials: M
authors.lastname: Ravanini
authors.forename: Renata A
authors.initials: RA
authors.lastname: Tassi
authors.forename: Antonella
authors.initials: A
authors.lastname: Ravaggi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bandiera
authors.forename: Chiara
authors.initials: C
authors.lastname: Romani
authors.forename: Laura
authors.initials: L
authors.lastname: Zanotti
authors.forename: Germana
authors.initials: G
authors.lastname: Tognon
authors.forename: Franco E
authors.initials: FE
authors.lastname: Odicino
authors.forename: Fabio
authors.initials: F
authors.lastname: Facchetti
authors.forename: Sergio
authors.initials: S
authors.lastname: Pecorelli
authors.forename: Alessandro D
authors.initials: AD
authors.lastname: Santin
mesh_terms: 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
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C499380:TACSTD2 protein, human