Macrophages, inflammation and risk of cervical intraepithelial neoplasia (CIN) progression--clinicopathological correlation

Gynecol Oncol. 2007 Apr;105(1):157-65. doi: 10.1016/j.ygyno.2006.11.023. Epub 2007 Jan 16.

Abstract

Objective: To evaluate the population of macrophages during the cervical malignant transformation and its influence in CIN outcome.

Methods: Biopsies from 26 normal cervix, 28 low-grade (LSIL), 30 high grade squamous intraepithelial lesions (HSIL) and 28 squamous cell carcinomas (SCC) were stained by H&E to assess inflammation and by immunohistochemistry with anti-CD68 to detect macrophages. The macrophage count was corrected for the epithelial and stromal compartments using appropriate software. Clinical and prospective follow-up data were also available.

Results: We identified that macrophage count increased linearly with disease progression (median count per case at x200 magnification: normal, 5.1; LSIL, 5.5; HSIL, 9.9; SCC, 14.5; P<0.001), that inflammation also increased (moderate-intense inflammation present in 25%, 46.1%, 58.4% and 89.3% of normal, LSIL, HSIL and SCC, respectively; P<0.001) and that macrophage count was independently associated with the lesion grade (P<0.001). Moreover, macrophages showed an increasing migration into the epithelium along with the progression of CIN to invasive cancer. Of the 24 LSIL cases with information available, followed-up for 805+/-140 days, 16 regressed, 6 persisted and 2 progressed. Age, high-risk HPV or inflammation were not risk factors for persistent/progressed LSIL in our cohort. However, LSIL that persisted or progressed showed a higher macrophage count (median of 10.8) than lesions that regressed (7; P=0.031).

Conclusions: The study on macrophages offers a potential approach for cervical cancer treatment, since macrophages are closely related to progression of CIN, and can be used as an applicable marker of such a risk.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / chemistry
  • Antigens, Differentiation, Myelomonocytic / chemistry
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / pathology*
  • Cell Transformation, Neoplastic / immunology
  • Cell Transformation, Neoplastic / pathology*
  • Cervical Intraepithelial Neoplasia / immunology
  • Cervical Intraepithelial Neoplasia / pathology*
  • Female
  • Humans
  • Immunohistochemistry
  • Inflammation / immunology
  • Inflammation / pathology
  • Macrophages / immunology
  • Macrophages / pathology*
  • Risk Factors
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / pathology*

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human