Differential expression of the monocyte chemoattractant protein-1 gene in human papillomavirus-16-infected squamous intraepithelial lesions and squamous cell carcinomas of the cervix uteri.

Monocyte chemoattractant protein (MCP)-1 is an important factor involved in the cross-talk between mononuclear cells and human papilloma-virus (HPV)-infected cervical epithelia. To prove the experimental model of a negative regulatory loop between the expression of the HPV oncogenes E6/E7 and the MCP-1 gene in vivo, we examined HPV-16-infected conization/hysterectomy specimens consisting of 6 low- and 6 high-grade squamous intraepithelial lesions (SILs) and 5 squamous cell carcinomas (SCCs) as well as the adjacent mucosa by isotopic RNA in situ hybridization. Langerhans cells and stromal macrophages were identified by the antibodies S-100 and PG-M1. E6/E7 expression was restricted to dysplastic or neoplastic keratinocytes, whereas MCP-1 transcripts were detectable in normal, dysplastic, and neoplastic epithelia, in endothelia, and in stromal macrophages. Langerhans cells were always negative. MCP-1 expression was predominant at the epithelial-mesenchymal junctions and especially intense when the stromal macrophage reaction was increased. Generally, the synchronous expression of E6/E7 and MCP-1 was very rare in SILs (2 of 12 cases). In high-grade SIL, MCP-1 expression was observed in 1 of 6 cases, whereas all lesions strongly hybridized with E6/E7 probes. In contrast, 4 of 5 SCCs re-expressed MCP-1, and 2 cases revealed marked transcriptional activities for both E6/E7 and MCP-1. Although preliminary, our observations lend support to the suggestion that the experimental model of transcriptional regulation and exclusion of either HPV E6/E7 or MCP-1 expression is especially pertinent to high-grade SIL, whereas in most SCCs, other environmental factors may influence this relationship.