title: Mammaglobin B is an independent prognostic marker in epithelial ovarian cancer and its expression is associated with reduced risk of disease recurrence.
abstract: BACKGROUND
  Traditional prognostic factors in epithelial ovarian cancer (EOC) are inadequate in predicting recurrence and long-term prognosis, but genome-wide cancer research has recently provided multiple potentially useful biomarkers. The gene codifying for Mammaglobin B (MGB-2) has been selected from our previous microarray analysis performed on 19 serous papillary epithelial ovarian cancers and its expression has been further investigated on multiple histological subtypes, both at mRNA and protein level. Since, to date, there is no information available on the prognostic significance of MGB-2 expression in cancer, the aim of this study was to determine its prognostic potential on survival in a large cohort of well-characterized EOC patients.
  
  
  METHODS
  MGB-2 expression was evaluated by quantitative real time-PCR in fresh-frozen tissue biopsies and was validated by immunohistochemistry in matched formalin fixed-paraffin embedded tissue samples derived from a total of 106 EOC patients and 27 controls. MGB-2 expression was then associated with the clinicopathologic features of the tumors and was correlated with clinical outcome.
  
  
  RESULTS
  MGB-2 expression was found significantly elevated in EOC compared to normal ovarian controls, both at mRNA and protein level. A good correlation was detected between MGB-2 expression data obtained by the two different techniques. MGB-2 expressing tumors were significantly associated with several clinicopathologic characteristics defining a less aggressive tumor behavior. Univariate survival analysis revealed a decreased risk for cancer-related death, recurrence and disease progression in MGB-2-expressing patients (p < 0.05). Moreover, multivariate analysis indicated that high expression levels of MGB-2 transcript (HR = 0.25, 95%, 0.08-0.75, p = 0.014) as well as positive immunostaining for the protein (HR = 0.41, 95%CI, 0.17-0.99, p = 0.048) had an independent prognostic value for disease-free survival.
  
  
  CONCLUSIONS
  This is the first report documenting that MGB-2 expression characterizes less aggressive forms of EOC and is correlated with a favorable outcome. These findings suggest that the determination of MGB-2, especially at molecular level, in EOC tissue obtained after primary surgery can provide additional prognostic information about the risk of recurrence.
authors.affiliation: Division of Gynecologic Oncology, Department Materno Infantile e Tecnologie Biomediche, University of Brescia, Brescia, Italy. renata.tassi03@gmail.com
authors.forename: Renata A
authors.initials: RA
authors.lastname: Tassi
authors.forename: Stefano
authors.initials: S
authors.lastname: Calza
authors.forename: Antonella
authors.initials: A
authors.lastname: Ravaggi
authors.forename: Eliana
authors.initials: E
authors.lastname: Bignotti
authors.forename: Franco E
authors.initials: FE
authors.lastname: Odicino
authors.forename: Germana
authors.initials: G
authors.lastname: Tognon
authors.forename: Carla
authors.initials: C
authors.lastname: Donzelli
authors.forename: Marcella
authors.initials: M
authors.lastname: Falchetti
authors.forename: Elisa
authors.initials: E
authors.lastname: Rossi
authors.forename: Paola
authors.initials: P
authors.lastname: Todeschini
authors.forename: Chiara
authors.initials: C
authors.lastname: Romani
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bandiera
authors.forename: Laura
authors.initials: L
authors.lastname: Zanotti
authors.forename: Sergio
authors.initials: S
authors.lastname: Pecorelli
authors.forename: Alessandro D
authors.initials: AD
authors.lastname: Santin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D015331:Cohort Studies; D004848:Epithelium / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D060788:Mammaglobin B; D008875:Middle Aged; D009185:Myelin Proteins / Q000096:biosynthesis* / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D011379:Prognosis; D011510:Proteolipids / Q000096:biosynthesis* / Q000502:physiology*; D012008:Recurrence; D012306:Risk; D060765:Secretoglobins; D014598:Uteroglobin / Q000096:biosynthesis* / Q000502:physiology*
chemical_list: D014408:Biomarkers, Tumor; D060788:Mammaglobin B; D009185:Myelin Proteins; D011510:Proteolipids; C556467:SCGB2A1 protein, human; D060765:Secretoglobins; D014598:Uteroglobin