title: Macrophages, inflammation and risk of cervical intraepithelial neoplasia (CIN) progression--clinicopathological correlation.
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.
authors.affiliation: Department of Obstetrics and Gynecology, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. hammes@cpovo.net
authors.forename: Luciano S
authors.initials: LS
authors.lastname: Hammes
authors.forename: Rajeshwar Rao
authors.initials: RR
authors.lastname: Tekmal
authors.forename: Paulo
authors.initials: P
authors.lastname: Naud
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Edelweiss
authors.forename: Nameer
authors.initials: N
authors.lastname: Kirma
authors.forename: Philip T
authors.initials: PT
authors.lastname: Valente
authors.forename: Kari J
authors.initials: KJ
authors.lastname: Syrjänen
authors.forename: João Sabino
authors.initials: JS
authors.lastname: Cunha-Filho
mesh_terms: D015703:Antigens, CD / Q000737:chemistry; D015214:Antigens, Differentiation, Myelomonocytic / Q000737:chemistry; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000276:immunology / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000473:pathology*; D002578:Uterine Cervical Dysplasia / Q000276:immunology / Q000473:pathology*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C067980:CD68 antigen, human; D000097382:CD68 Molecule