Hammes Luciano S, Tekmal Rajeshwar Rao, Naud Paulo, Edelweiss Maria Isabel, Kirma Nameer, Valente Philip T, Syrjänen Kari J, Cunha-Filho João Sabino
Department of Obstetrics and Gynecology, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Gynecol Oncol. 2007 Apr;105(1):157-65. doi: 10.1016/j.ygyno.2006.11.023. Epub 2007 Jan 16.
To evaluate the population of macrophages during the cervical malignant transformation and its influence in CIN outcome.
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.
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).
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.
评估宫颈恶性转化过程中巨噬细胞的数量及其对宫颈上皮内瘤变（CIN）转归的影响。
对26例正常宫颈、28例低级别（LSIL）、30例高级别鳞状上皮内病变（HSIL）和28例鳞状细胞癌（SCC）的活检组织进行苏木精-伊红（H&E）染色以评估炎症情况，并用抗CD68免疫组织化学法检测巨噬细胞。使用适当软件对上皮和间质成分中的巨噬细胞计数进行校正。同时还获取了临床和前瞻性随访数据。
我们发现巨噬细胞计数随疾病进展呈线性增加（x200放大倍数下每例中位数计数：正常为5.1；LSIL为5.5；HSIL为9.9；SCC为14.5；P<0.001），炎症也增加（正常、LSIL、HSIL和SCC中分别有25%、46.1%、58.4%和89.3%存在中度至重度炎症；P<0.001），且巨噬细胞计数与病变级别独立相关（P<0.001）。此外，随着CIN进展为浸润癌，巨噬细胞向上皮的迁移增加。在有可用信息的24例LSIL病例中，随访805±140天，16例消退，6例持续存在，2例进展。在我们的队列中，年龄、高危型人乳头瘤病毒（HPV）或炎症不是LSIL持续存在/进展的危险因素。然而，持续存在或进展的LSIL的巨噬细胞计数（中位数为10.．8）高于消退的病变（7；P=0.031）。
对巨噬细胞的研究为宫颈癌治疗提供了一种潜在方法, 因为巨噬细胞与CIN进展密切相关，可作为这种风险的适用标志物。
