Expression pattern of the CXCL12/CXCR4-CXCR7 trio in Kaposi sarcoma skin lesions

Summary Background Recent studies have independently implicated the chemokine CXCL12 and its receptors, CXCR4 and CXCR7, in the pathophysiology of Kaposi sarcoma (KS). Objectives We investigated whether the CXCL12/CXCR4–CXCR7 protein trio could constitute KS biomarkers. Methods Endothelial and spindle cells positive for CXCL12/CXCR4–CXCR7, human herpesvirus‐8 latency‐associated nuclear antigen (LANA), Ki67 antigen (proliferation) and vascular endothelial growth factor (VEGF) were quantitated in skin lesions from patients with AIDS‐associated KS, patients with classic KS and patients with angiomas, using immunohistochemistry and quantitative image analysis (16, 21 and 20 skin lesions, respectively). Plasma CXCL12 concentrations were measured by enzyme‐linked immunosorbent assay from 20 patients with AIDS‐KS, 12 HIV‐infected patients without KS and 13 healthy donors' samples. Results Cells positive for CXCL12, CXCR4, CXCR7, LANA, Ki67 and VEGF were significantly enriched in patients with AIDS‐associated KS and classic KS vs. angiomas (P < 0·001), and in nodular vs. macular/papular KS lesions (P < 0·05). CXCL12, CXCR4 and CXCR7 detection correlated with LANA, Ki67 and VEGF detection (r > 0·4; P < 0·05). However, plasma CXCL12 concentrations did not differ between patients with AIDS‐associated KS, HIV‐infected patients without KS, and healthy donors. Conclusions The CXCL12/CXCR4–CXCR7 trio is upregulated in KS and correlates with KS pathophysiological markers and the severity of skin lesions. Histological assessment of the CXCL12 axis could serve as a valuable biomarker for KS diagnosis and progression. What's already known about this topic? Chemokines play important roles in the pathogenesis of Kaposi sarcoma (KS). Recent studies have independently implicated CXCL12, CXCR4 and CXCR7 in KS pathophysiology. What does this study add? We observed a simultaneous CXCL12/CXCR4–CXCR7 upregulation in AIDS‐associated KS and classic KS lesions that correlates with both the lesion severity and detection of latency‐associated nuclear antigen, Ki67 and vascular endothelial growth factor. The detection of the CXCL12/CXCR4–CXCR7 trio could be used as a tissue biomarker for KS lesions. What is the translational message? The CXCL12 axis has been shown to be involved in chronic skin inflammation and inflammatory angiogenesis; two components of KS pathogenesis. Histological detection of the CXCL12 axis could allow KS classification, patient stratification or KS progression predi