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

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 ×200 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.