Mammaglobin B is an independent prognostic marker in epithelial ovarian cancer and its expression is associated with reduced risk of disease recurrence.
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.
Tassi
Renata A
RA
Division of Gynecologic Oncology, Department Materno Infantile e Tecnologie Biomediche, University of Brescia, Brescia, Italy. renata.tassi03@gmail.com
Calza
Stefano
S
Ravaggi
Antonella
A
Bignotti
Eliana
E
Odicino
Franco E
FE
Tognon
Germana
G
Donzelli
Carla
C
Falchetti
Marcella
M
Rossi
Elisa
E
Todeschini
Paola
P
Romani
Chiara
C
Bandiera
Elisabetta
E
Zanotti
Laura
L
Pecorelli
Sergio
S
Santin
Alessandro D
AD
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*
D014408:Biomarkers, Tumor; D060788:Mammaglobin B; D009185:Myelin Proteins; D011510:Proteolipids; C556467:SCGB2A1 protein, human; D060765:Secretoglobins; D014598:Uteroglobin