Folate receptor-α expression in resectable hepatic colorectal cancer metastases: Patterns and significance Journal Article


Authors: D'Angelica, M.; Ammori, J.; Gonen, M.; Klimstra, D. S.; Low, P. S.; Murphy, L.; Weiser, M. R.; Paty, P. B.; Fong, Y.; DeMatteo, R. P.; Allen, P.; Jarnagin, W. R.; Shia, J.
Article Title: Folate receptor-α expression in resectable hepatic colorectal cancer metastases: Patterns and significance
Abstract: Folate receptor alpha (FRα), encoded by folate receptor 1 (adult) gene, has emerged as a cancer biomarker and potential therapeutic target. In addition, its expression in tumors may offer prognostic information. The aim of this study was to assess the prognostic value of FRα expression and other common molecular markers in resected liver metastases from colorectal cancer. To maximize potential biological differences, we selected two groups of patients with markedly different outcomes as study subjects. Immunohistochemical analysis of FRα expression and other common markers (thymidylate synthase, p53, p27, BCL2, ki67, MLH1, MSH2 and MGMT) on tissue microarrays was carried out on samples from 160 patients; 56 patients survived at least 10 years following liver resection, and 104 died within 2 years of surgery. These markers were evaluated and compared with standard clinical predictors of outcome including a previously validated clinical risk score. Our results showed that in addition to known clinical risk factors, FRα positivity was significantly associated with the early death group (32% compared with 13%; P=0.03). None of the other common molecular markers were differentially expressed between the two groups. On multivariate analysis, clinical risk score, margin status and FRα expression were independently associated with outcome. Specific multivariate comparisons confirmed that FRα expression was associated with outcome independent of the clinical risk score and margin. These data demonstrate that FRα expression is present in a subset of resected hepatic colorectal cancer metastases, and this marker is independently associated with survival after hepatic resection. The prognostic value of FRα expression and the utility of FRα-targeted therapies in stage-IV colorectal cancer patients deserve further exploration. © 2011 USCAP, Inc All rights reserved.
Keywords: immunohistochemistry; adult; cancer survival; human tissue; protein expression; aged; cancer surgery; major clinical study; advanced cancer; cancer risk; outcome assessment; colorectal cancer; ki 67 antigen; protein bcl 2; protein p53; cancer mortality; liver metastasis; protein p27; scoring system; liver resection; predictor variable; methylated dna protein cysteine methyltransferase; tissue microarray; thymidylate synthase; protein mlh1; protein msh2; folate receptor 1; folate receptor 1 (adult); folate-targeted therapy
Journal Title: Modern Pathology
Volume: 24
Issue: 9
ISSN: 0893-3952
Publisher: Nature Research  
Date Published: 2011-09-01
Start Page: 1221
End Page: 1228
Language: English
DOI: 10.1038/modpathol.2011.82
PROVIDER: scopus
PUBMED: 21572402
DOI/URL:
Notes: --- - "Export Date: 3 October 2011" - "CODEN: MODPE" - "Source: Scopus"
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MSK Authors
  1. Philip B Paty
    496 Paty
  2. Ronald P DeMatteo
    637 DeMatteo
  3. Mithat Gonen
    1028 Gonen
  4. David S Klimstra
    978 Klimstra
  5. Jinru Shia
    717 Shia
  6. Martin R Weiser
    534 Weiser
  7. Peter Allen
    501 Allen
  8. William R Jarnagin
    903 Jarnagin
  9. Yuman Fong
    775 Fong
  10. John Brian Ammori
    9 Ammori