Overexpression of folate binding protein is associated with shortened progression-free survival in uterine adenocarcinomas.
OBJECTIVE
Oligonucleotide array and tissue microarray analysis (TMA) by our group has revealed that folate binding protein (FOLR1) is overexpressed in some types of uterine cancer, particularly tumors with serous histology. Since FOLR1 overexpression is a frequent event in some types of endometrial carcinoma, we examined the relationship between FOLR1 overexpression and clinical and pathologic features to determine its prognostic relevance.


METHODS
A tissue microarray (TMA) comprised of primary tumor specimens from 485 patients diagnosed with endometrial adenocarcinoma was used to identify cases characterized by FOLR1 overexpression. A proportional hazards model was used to evaluate the association of FOLR1 overexpression with progression-free survival while accounting for confounding influences.


RESULTS
Overexpression of FOLR1 was observed in 50/292 (17%) cases and was seen more often in poorly differentiated cancers (22/90 [24%], p=0.051) and tumors with serous histology (16/32 [50%], p<0.001). A shorter progression-free survival was noted in patients with FOLR1 overexpression (log-rank p=0.016) that persisted when the data were limited to patients with stage III/IV disease (log-rank p=0.021) or serous tumors (log-rank p=0.020). Multivariate Cox regression analysis revealed that patients with FOLR1 overexpression had a shorter progression-free survival (H.R. 2.14; 95% CI 1.07-4.28) even when controlling for stage, grade, myometrial invasion and adjuvant chemotherapy.


CONCLUSIONS
Our data show that FOLR1 overexpression is not only a biomarker associated with endometrial cancer, but it also appears to be a prognostic factor associated with adverse outcome. These findings suggest that FOLR1 may be an appealing target for biological therapies in some types of endometrial carcinomas.
Allard
Jay E
JE
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology and the United States Military Cancer Institute, Walter Reed Army Medical Center, Washington, DC, USA.
Risinger
John I
JI
Morrison
Carl
C
Young
Gregory
G
Rose
G Scott
GS
Fowler
Jeff
J
Berchuck
Andrew
A
Maxwell
G Larry
GL
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002352:Carrier Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D005260:Female; D058975:Folate Receptor 1; D058973:Folate Receptors, GPI-Anchored; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015996:Survival Rate; D046888:Tissue Array Analysis; D014594:Uterine Neoplasms / Q000378:metabolism
D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C548696:FOLR1 protein, human; D058975:Folate Receptor 1; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface