Folate receptor alpha as a tumor target in epithelial ovarian cancer.
OBJECTIVE
Folate receptor alpha (FRalpha) is a folate-binding protein overexpressed on ovarian and several other epithelial malignancies that can be used as a target for imaging and therapeutic strategies. The goal of this study is to improve historical data that lack specific information about FRalpha expression in rare histological subtypes, primary disease versus metastatic foci, and recurrent disease.


METHODS
FRalpha expression was analyzed by immunohistochemistry on 186 primary and 27 recurrent ovarian tumors, including 24 pairs of samples obtained from the same individuals at diagnosis and at secondary debulking surgery. For 20 of the 186 primaries, simultaneous metastatic foci were also analyzed. FRalpha staining was analyzed in light of disease morphology, stage, grade, debulking status, and time from diagnosis to recurrence and death.


RESULTS
FRalpha expression was apparent in 134 of 186 (72%) primary and 22 of 27 (81.5%) recurrent ovarian tumors. In 21 of 24 (87.5%) matched specimens, recurrent tumors reflected the FRalpha status detected at diagnosis. Metastatic foci were similar to primary tumors in FRalpha staining. FRalpha status was not associated with time to recurrence or overall survival in either univariate or multivariable analyses.


CONCLUSIONS
FRalpha expression occurs frequently, especially in the common high-grade, high-stage serous tumors that are most likely to recur. New findings from this study show that FRalpha expression is maintained on metastatic foci and recurrent tumors, suggesting that novel folate-targeted therapies may hold promise for the majority of women with either newly diagnosed or recurrent ovarian cancer.
Kalli
Kimberly R
KR
Division of Medical Oncology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Oberg
Ann L
AL
Keeney
Gary L
GL
Christianson
Teresa J H
TJ
Low
Philip S
PS
Knutson
Keith L
KL
Hartmann
Lynn C
LC
D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018269:Carcinoma, Endometrioid / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008499:Medical Records; D008875:Middle Aged; D008910:Minnesota; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D016019:Survival Analysis
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface