J Cancer 2017; 8(18):3868-3875. doi:10.7150/jca.21444

Research Paper

Clinical Significance of CD163+ and CD68+ Tumor-associated Macrophages in High-risk HPV-related Cervical Cancer

Xiao-Jing Chen1*, Ling-Fei Han4*, Xiang-Guang Wu1*, Wen-Fei Wei1, Lan-Fang Wu5, Hong-Yan Yi1, Rui-Ming Yan1, Xiang-yang Bai1, Mei Zhong1, Yan-hong Yu1, Li Liang3✉, Wei Wang1,2✉

1. Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University/The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China
2. Department of Obstetrics and Gynecology, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, People's Republic of China
3. Department of Pathology, Nanfang Hospital, Southern Medical University/The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China
4. Department of Minimally Invasive Gynecologic Surgery, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China
5. Department of Obstetrics and Gynecology, the Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China
* Xiao-Jing Chen, Ling-Fei Han, and Xiang-Guang Wu contributed equally to this work.

Abstract

Objective. To explore the influence of M2-polarized tumor-associated macrophages (TAMs) on high-risk human papillomavirus (hr-HPV)-related cervical carcinogenesis and metastasis.

Methods. CD68+ and CD163+ macrophages were examined immunohistochemically in a series of 130 samples, including 26 cases of normal cervical tissues, 59 cases of cervical intraepithelial neoplasia (CIN), and 45 cases of squamous cell carcinoma (SCC), and the results were statistically analyzed. The macrophage count was corrected for the epithelial and stromal compartments respectively. Clinical data were also obtained.

Results. High counts of CD68+ and CD163+ macrophages were associated with hr-HPV infection (both p < 0.05) and positively correlated with cervical carcinogenesis (Spearman's rho = 0.478, p = 0.000; Spearman's rho = 0.676, p =0.000, respectively). The immunostaining pattern of CD163 exhibited clearer background than that of CD68. CD163+ macrophages showed a more obviously increasing migration into the epithelium along with the progression of CIN to invasive cancer. Notably, a high index of CD163+ macrophages was significantly associated with higher FIGO stages (p = 0.009) and lymph node metastasis (p = 0.012), but a similar finding was not found for CD68+ macrophages (p = 0.067, p = 0.079, respectively).

Conclusions. Our study supported a critical role of TAMs as a prospective predictor for hr-HPV-related cervical carcinogenesis. CD163, as a promising TAMs marker, is superior to CD68 for predicting the malignant transformation and metastatic potential of cervical cancer.

Keywords: CD68, CD163, cervical cancer, human papillomavirus (HPV), tumor-associated macrophages (TAMs), tumor microenvironment (TME)

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How to cite this article:
Chen XJ, Han LF, Wu XG, Wei WF, Wu LF, Yi HY, Yan RM, Bai Xy, Zhong M, Yu Yh, Liang L, Wang W. Clinical Significance of CD163+ and CD68+ Tumor-associated Macrophages in High-risk HPV-related Cervical Cancer. J Cancer 2017; 8(18):3868-3875. doi:10.7150/jca.21444. Available from http://www.jcancer.org/v08p3868.htm