Tissue invasive macrophage density is correlated with prognosis in cholangiocarcinoma

  • Authors:
    • Chutima Subimerb
    • Somchai Pinlaor
    • Narong Khuntikeo
    • Chanvit Leelayuwat
    • Alanna Morris
    • Michael S. McGrath
    • Sopit Wongkham
  • Corresponding author:
  • View Affiliations

  • Published online on: Thursday, July 1, 2010
  • Pages: 597-605
  • DOI: 10.3892/mmr_00000303

Abstract

Cholangiocarcinoma (CCA) is a high metastatic cancer with no effective treatment. Here, the pro-metastatic action of tissue macrophages in CCA is demonstrated and suggested as a prognostic marker and novel target for the therapeutic intervention of CCA. Fifty CCA tissues were immunohistochemically stained with a marker for reactive/infiltrating monocytes/macrophages (MAC387) and matrix metalloproteinase (MMP)-9. The antigenic densities in positively-stained cells along the leading edge of tumors were scored. Correlations between the densities of MAC387, MMP-9-positive cells, clinicopathological features and patient survival were investigated. High densities of MAC387-positive cells were detected in more than 60% of the CCA tissues. This was significantly associated with poor prognosis parameters (non-papillary and mass-forming type CCA). Overall survival was worst in patients with high-density MAC387-positive cells. Double immunofluorescent staining indicated that MAC387-positive cells co-expressed MMP-9. Immunohistochemical staining of MMP-9 in serial sections of CCA tissues indicated that MMP-9 was rarely expressed in CCA tumor cells, but highly expressed in MAC387-positive cells and polymorphonucleated infiltrating cells. Patients with high tissue expression levels of MAC387 in combination with MMP-9-expressing cells had the worst survival. These factors were found to be independent predictors of the post-resectional survival of CCA patients. Since CCA tumor cells rarely expressed MMP-9, it is likely that tissue macrophages are critical for degrading the extracellular matrix and for facilitating tumor metastasis. They may therefore serve as a prognostic marker for poor clinical outcome, and represent novel targets for the therapeutic intervention of CCA.
Journal Cover

July 2010
Volume 3 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

2013 Impact Factor: 1.484
Ranked #59/122 Medicine Research and Experimental
(total number of cites)

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APA
Subimerb, C., Pinlaor, S., Khuntikeo, N., Leelayuwat, C., Morris, A., McGrath, M.S., & Wongkham, S. (2010). Tissue invasive macrophage density is correlated with prognosis in cholangiocarcinoma . Molecular Medicine Reports, 3, 597-605. http://dx.doi.org/10.3892/mmr_00000303
MLA
Subimerb, C., Pinlaor, S., Khuntikeo, N., Leelayuwat, C., Morris, A., McGrath, M. S., Wongkham, S."Tissue invasive macrophage density is correlated with prognosis in cholangiocarcinoma ". Molecular Medicine Reports 3.4 (2010): 597-605.
Chicago
Subimerb, C., Pinlaor, S., Khuntikeo, N., Leelayuwat, C., Morris, A., McGrath, M. S., Wongkham, S."Tissue invasive macrophage density is correlated with prognosis in cholangiocarcinoma ". Molecular Medicine Reports 3, no. 4 (2010): 597-605. http://dx.doi.org/10.3892/mmr_00000303