M2-macrophage infiltration and macrophage traits of tumor cells in urinary bladder cancer

Urol Oncol. 2018 Apr;36(4):159.e19-159.e26. doi: 10.1016/j.urolonc.2017.11.020. Epub 2017 Dec 26.

Abstract

Background: Tumor-associated macrophages (TAMs) constitute a subset of nonneoplastic cells in tumor stroma and influence cancer progression in solid tumors. The clinical significance of TAMs in urinary bladder cancer (UBC) is controversial.

Methods: We prospectively studied 103 patients with stage pT1-T4 UBC treated with cystectomy and pelvic lymph node dissection. Tumor sections were immunostained with M2-specific macrophage marker CD163 and proliferation marker Ki-67. The expression of these markers in cancer cells as well as macrophage infiltration (MI) in tumor stroma was analyzed in relation to clinical data and outcome.

Results: The mean rate of CD163 and Ki-67 expressed by cancer cells were 35% and 78%, respectively. With borderline significance, MI was associated with lower rate of lymph node metastasis (P = 0.06). CD163 expression in cancer cells was proportional to MI (P<0.014). Patients with CD163-positive tumors and strong MI had significantly longer cancer-specific survival (CSS) (76 months), compared to patient with CD163-positive tumors and weak MI (28 months) (P = 0.02).

Conclusions: M2-specific MI tends to be inversely correlated with LN metastasis and improved CSS in UBC. MI might have protective impact in CD163-positive tumors. Expression of CD163 in cancer cells is significantly correlated with MI and might have a tumor promoting impact.

Keywords: Bladder cancer; CD163; Ki-67; Lymph node metastasis; Macrophage traits in tumor cells; Tumor-associated macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, CD / immunology
  • Antigens, CD / metabolism*
  • Antigens, Differentiation, Myelomonocytic / immunology
  • Antigens, Differentiation, Myelomonocytic / metabolism*
  • Cystectomy
  • Female
  • Humans
  • Lymphatic Metastasis
  • Macrophages / immunology*
  • Male
  • Middle Aged
  • Prospective Studies
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism*
  • Stromal Cells / immunology
  • Stromal Cells / metabolism
  • Survival Rate
  • Tumor Microenvironment / immunology
  • Urinary Bladder / cytology*
  • Urinary Bladder / immunology
  • Urinary Bladder / pathology
  • Urinary Bladder / surgery
  • Urinary Bladder Neoplasms / immunology*
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / surgery

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • Receptors, Cell Surface