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
  • 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., & Wongkham, S. (2010). Tissue invasive macrophage density is correlated with prognosis in cholangiocarcinoma . Molecular Medicine Reports, 3(4), 597-605.
MLA
Subimerb, Pinlaor, Khuntikeo, Leelayuwat, Morris, McGrath, and Sopit Wongkham. "Tissue invasive macrophage density is correlated with prognosis in cholangiocarcinoma ." Molecular Medicine Reports Molecular Medicine Reports 3.4 (2010): 597-605.
Chicago
Subimerb, Pinlaor, Khuntikeo, Leelayuwat, Morris, McGrath, and Sopit Wongkham. "Tissue invasive macrophage density is correlated with prognosis in cholangiocarcinoma ." Molecular Medicine Reports Molecular Medicine Reports 3 no. 4 (2010): 597-605.