Overexpression of folate binding protein is associated with shortened progression-free survival in uterine adenocarcinomas

Objectives. 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 progress ion-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. (C) 2007 Published by Elsevier Inc.