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Overexpression of folate binding protein and mesothelin are associated with uterine serous carcinoma.

Publication ,  Journal Article
Dainty, LA; Risinger, JI; Morrison, C; Chandramouli, GVR; Bidus, MA; Zahn, C; Rose, GS; Fowler, J; Berchuck, A; Maxwell, GL
Published in: Gynecol Oncol
June 2007

PURPOSE: Folate receptor alpha (FOLR1) is a membrane bound receptor involved in the transport of folate as well as other regulatory cellular processes. The purpose of this study was to examine the expression of FOLR1 in uterine cancers and to identify changes in gene expression that are associated with overexpression of FOLR1. EXPERIMENTAL DESIGN: Fifty-eight frozen uterine cancer specimens were stained for FOLR1 using immunohistochemistry and results were correlated with transcript expression noted on quantitative PCR. Total RNA from 16 cases of uterine serous carcinoma (USC) was analyzed for gene expression using the Affymetrix HG-U133A and HG-U133B GeneChip set. USCs overexpressing FOLR1 were compared to cancers with an absence of FOLR1 using binary comparison and template matching of data was used to identify genes that correlate with FOLR1 expression. Selected targets from this analysis were evaluated by quantitative PCR as well as in an independent set of USC represented in quadruplicate on a tissue microarray (TMA). RESULTS: Overexpression of FOLR1 was observed in 11/16 (69%) of USC and 0/10 normal endometrium cases using frozen tissue specimens. Binary comparison between FOLR1 positive and negative cases identified 121 genes altered by 2-fold at p<0.01 of which 45 are well correlated with FOLR1 expression pattern. Using quantitative PCR, both mesothelin (MSLN) and PTGS1 (COX1) were significantly increased in FOLR1 overexpressing tumors (p=0.014 and p=0.006 respectively). TMA confirmed that overexpression of FOLR1 and MSLN respectively occurred in 23/48 (48%) and 17/54 (32%) of pure USC. CONCLUSION: Both FOLR1 and MSLN are cell surface targets that are co-expressed at high levels in USC and are appealing targets for biologic therapy.

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Published In

Gynecol Oncol

DOI

ISSN

0090-8258

Publication Date

June 2007

Volume

105

Issue

3

Start / End Page

563 / 570

Location

United States

Related Subject Headings

  • Uterine Neoplasms
  • Receptors, Cell Surface
  • RNA, Messenger
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Oligonucleotide Array Sequence Analysis
  • Mixed Tumor, Mullerian
  • Mesothelin
  • Membrane Glycoproteins
  • Immunohistochemistry
 

Citation

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MLA
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Dainty, L. A., Risinger, J. I., Morrison, C., Chandramouli, G. V. R., Bidus, M. A., Zahn, C., … Maxwell, G. L. (2007). Overexpression of folate binding protein and mesothelin are associated with uterine serous carcinoma. Gynecol Oncol, 105(3), 563–570. https://doi.org/10.1016/j.ygyno.2006.10.063
Dainty, Louis A., John I. Risinger, Carl Morrison, G. V. R. Chandramouli, Michael A. Bidus, Chris Zahn, G Scott Rose, Jeff Fowler, Andrew Berchuck, and G Larry Maxwell. “Overexpression of folate binding protein and mesothelin are associated with uterine serous carcinoma.Gynecol Oncol 105, no. 3 (June 2007): 563–70. https://doi.org/10.1016/j.ygyno.2006.10.063.
Dainty LA, Risinger JI, Morrison C, Chandramouli GVR, Bidus MA, Zahn C, et al. Overexpression of folate binding protein and mesothelin are associated with uterine serous carcinoma. Gynecol Oncol. 2007 Jun;105(3):563–70.
Dainty, Louis A., et al. “Overexpression of folate binding protein and mesothelin are associated with uterine serous carcinoma.Gynecol Oncol, vol. 105, no. 3, June 2007, pp. 563–70. Pubmed, doi:10.1016/j.ygyno.2006.10.063.
Dainty LA, Risinger JI, Morrison C, Chandramouli GVR, Bidus MA, Zahn C, Rose GS, Fowler J, Berchuck A, Maxwell GL. Overexpression of folate binding protein and mesothelin are associated with uterine serous carcinoma. Gynecol Oncol. 2007 Jun;105(3):563–570.
Journal cover image

Published In

Gynecol Oncol

DOI

ISSN

0090-8258

Publication Date

June 2007

Volume

105

Issue

3

Start / End Page

563 / 570

Location

United States

Related Subject Headings

  • Uterine Neoplasms
  • Receptors, Cell Surface
  • RNA, Messenger
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Oligonucleotide Array Sequence Analysis
  • Mixed Tumor, Mullerian
  • Mesothelin
  • Membrane Glycoproteins
  • Immunohistochemistry