Multivitamin and Alcohol Intake and Folate Receptor α Expression in Ovarian Cancer

Kelemen, Linda E.; Sellers, Thomas A.; Keeney, Gary L.; Lingle, Wilma L.

doi:10.1158/1055-9965.epi-05-0260

Cited by 21 publications

(25 citation statements)

References 24 publications

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“…An additional negative control was liver tissue on each TMA. Positive controls were ovarian cancer specimens (not included in this study) that had previously been identified as expressing FRα using a polyclonal antibody [15]. After washing the slides, signals were detected using the mouse MACH3 system (Biocare Medical, Walnut Creek, CA).…”

Section: Immunohistochemistrymentioning

confidence: 99%

Folate receptor alpha as a tumor target in epithelial ovarian cancer

Kalli¹,

Oberg²,

Keeney³

et al. 2008

Gynecologic Oncology

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Objectives-Folate receptor α (FRα) 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 FRα expression in rare histological subtypes, primary disease versus metastatic foci, and recurrent disease.Methods-FRα 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. FRα staining was analyzed in light of disease morphology, stage, grade, debulking status, and time from diagnosis to recurrence and death.Results-FRα 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 FRα status detected at diagnosis. Metastatic foci were similar to primary tumors in FRα staining. FRα status was not associated with time to recurrence or overall survival in either univariate or multivariable analyses.Conclusion-FRα 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 FRα 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.

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Section: Immunohistochemistrymentioning

confidence: 99%

Folate receptor alpha as a tumor target in epithelial ovarian cancer

Kalli¹,

Oberg²,

Keeney³

et al. 2008

Gynecologic Oncology

Self Cite

386

271

View full text Add to dashboard Cite

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“…In healthy individuals, FOLR1 expression is often limited to the apical surfaces of epithelium in the lung, kidney and choroid plexus but is overexpressed in a variety of solid tumours such as ovarian cancer, non-small cell lung cancer, breast cancer, kidney cancer and high-grade osteosarcoma (26–29). It is hypothesized that FOLR1 upregulation in solid malignancies is due to the increased metabolic requirements for folates to fuel nucleic acid synthesis and cellular growth (30). The biological relevance of folates, to carcinogenesis has thus made FOLR1 an attractive therapeutic target in ovarian cancer, especially those of epithelial etiology, where FOLR1 is upregulated in approximately 90% of the cases (28).…”

Section: Introductionmentioning

confidence: 99%

Folate-receptor 1 (FOLR1) protein is elevated in the serum of ovarian cancer patients

Leung

Dimitromanolakis

Kobayashi

et al. 2013

Clinical Biochemistry

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Objectives Ovarian cancer is the most lethal gynecological malignancy in North America. Although survival rates are high when the disease is diagnosed at an early stage, this decreases exponentially in late-stage diagnoses. As such, there is a need for novel early detection biomarkers. Through an integrated approach to ovarian cancer biomarker discovery that combines proteomics with transcriptomics and bioinformatics, our laboratory has identified folate-receptor 1 (FOLR1) and Dickkopf-related protein 3 (Dkk-3) as putative biomarkers. The objective of this study was to measure the levels of FOLR1 and Dkk-3 in the serum of patients with ovarian cancer, benign gynecological conditions and healthy women. Design and Methods FOLR1 and Dkk-3 were analyzed in serum of 100 ovarian cancer patients, 100 patients with benign gynecological conditions, and 100 healthy women using enzyme-linked immunosorbent assays (ELISAs). All specimens were analyzed in triplicate. Results FOLR1 was significantly elevated in the serum of ovarian cancer patients compared to serum of both healthy controls (p < 0.0001) and patients with benign gynecological conditions (p < 0.0001). Furthermore, FOLR1 was strongly correlated with CA125 as both were elevated in the serous histotype and in late-stage disease. FOLR1 did not outperform CA125 in receiver operating characteristic curve analysis and there was no significant complementarity between the two markers. Dkk-3 was not significantly different between the three serum cohorts and was not correlated with CA125. Conclusions FOLR1 is a new biomarker for ovarian cancer which correlates closely with CA125. The role of FOLR1 in the pathogenesis of ovarian cancer warrants further investigation.

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“…A high dietary folate intake has been reported to associate with a lower risk of developing ovarian cancers, in particular, those who consume alcohol [6], [7], [8], [9]. It is closely related to its function on DNA synthesis and its involvement in the related methionine metabolic pathway essential for DNA methylation.…”

Section: Introductionmentioning

confidence: 99%

Paradoxical Impact of Two Folate Receptors, FRα and RFC, in Ovarian Cancer: Effect on Cell Proliferation, Invasion and Clinical Outcome

et al. 2012

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Despite being an essential vitamin, folate has been implicated to enhance tumor growth, as evidenced by reports on overexpression of folate receptor alpha (FRα) in carcinomas. The role of another folate transporter, reduced folate carrier (RFC), is largely unknown. This study investigated the roles of folate, FRα and RFC in ovarian cancers. We demonstrated FRα mRNA and protein overexpression and reduced RFC expression in association with FRα gene amplification and RFC promoter hypermethylation, respectively. FRα overexpression was associated with tumor progression while RFC expression incurred a favorable clinical outcome. Such reciprocal expression pattern was also observed in ovarian cancer cell lines. Folate was shown to promote cancer cell proliferation, migration and invasion in vitro, and down-regulate E-cadherin expression. This effect was blocked after either stable knockdown of FRα or ectopic overexpression of RFC. This hitherto unreported phenomenon suggests that, RFC can serve as a balancing partner of FRα and confer a protective effect in patients with high FRα-expressing ovarian carcinomas, as evidenced by their prolonged overall and disease-free survivals. In conclusion, we report on the paradoxical impact of FRα (putative oncogenic) and RFC (putative tumor suppressive) in human malignancies. FRα and RFC may potentially be explored as therapeutic target or prognostic marker respectively. We recommend caution and additional research on folate supplements in cancer patients.

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Multivitamin and Alcohol Intake and Folate Receptor α Expression in Ovarian Cancer

Cited by 21 publications

References 24 publications

Folate receptor alpha as a tumor target in epithelial ovarian cancer

Folate receptor alpha as a tumor target in epithelial ovarian cancer

Folate-receptor 1 (FOLR1) protein is elevated in the serum of ovarian cancer patients

Paradoxical Impact of Two Folate Receptors, FRα and RFC, in Ovarian Cancer: Effect on Cell Proliferation, Invasion and Clinical Outcome

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