GPR30 predicts poor survival for ovarian cancer.
OBJECTIVE
GPR30 is a 7-transmembrane G protein-coupled estrogen receptor that functions alongside traditional estrogen receptors to regulate cellular responses to estrogen. Recent studies suggest that GPR30 expression is linked to lower survival rates in endometrial and breast cancer. This study was conducted to evaluate GPR30 expression in ovarian tumors.


METHODS
GPR30 expression was analyzed using immunohistochemistry and archival specimens from 45 patients with ovarian tumors of low malignant potential (LMP) and 89 patients with epithelial ovarian cancer (EOC). Expression, defined as above or below the median (intensity times the percentage of positive epithelial cells) was correlated with predictors of adverse outcome and survival.


RESULTS
GPR30 expression above the median was observed more frequently in EOC than in LMP tumors (48.3% vs. 20%, p=0.002), and in EOC was associated with lower 5-year survival rates (44.2% vs. 82.6%, Log-rank p<0.001). Tumor grade and FIGO stage, the other significant predictors of survival, were used to stratify cases into "high risk" and "low risk" groups. The 5-year survival rate for "low risk" EOC (all grade 1 and Stage I/II, grade 2) was 100%. In "high risk" EOC (all grade 3 and Stage III/IV, grade 2), the difference in 5-year survival by GPR 30 expression was significant (33.3% vs. 72.4%, p=0.001).


CONCLUSIONS
The novel estrogen-responsive receptor GPR30 is preferentially expressed in "high risk" EOC and is associated with lower survival rates. Further investigation of GPR30 as a potential target for therapeutic intervention in high risk EOC is warranted.
Smith
Harriet O
HO
Department of Obstetrics and Gynecology and Women's Health, Division of Gynecologic Oncology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY 10461-2376, USA. hasmith@montfiore.org
Arias-Pulido
Hugo
H
Kuo
Dennis Y
DY
Howard
Tamara
T
Qualls
Clifford R
CR
Lee
Sang-Joon
SJ
Verschraegen
Claire F
CF
Hathaway
Helen J
HJ
Joste
Nancy E
NE
Prossnitz
Eric R
ER
D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis*; D015996:Survival Rate
D014408:Biomarkers, Tumor; C109584:GPER1 protein, human; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled