Monocyte-chemo-attractant-protein-1 (mcp-1)-gene expression in cervical intra-epithelial neoplasias and cervical carcinomas

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Abstract
Chemokines play a central role in the chemotactic activation of immunological effector cells. One of the currently best characterized chemokines is the monocyte‐chemo‐attractant protein‐1 (MCP‐1), which is involved in the cross‐talk with cells of the monocyte‐macrophage lineage. Since macrophages and macrophage‐derived cytokines appear to be important in the transcriptional regulation of “high‐risk” types of human papillomaviruses (HPV), we monitored MCP‐1 expression by in situ hybridization (ISH) in histologically distinct stages of cervical intra‐epithelial neoplasms (CIN), cervical cancer and non‐HPV‐associated cases of erosive endocervicitis. Here, we demonstrate that high‐grade dysplasia (CIN III, n = 9) completely lacks both MCP‐1 expression and CD68+‐macrophage infiltration, while MCP‐1‐specific signals were occasionally detectable in one out of 5 CIN‐II and in one out of 3 CIN‐I lesions. Inspection of hyperplastic squamous epithelium adjacent to cervical carcinomas reveals high MCP‐1 expression and accumulation of infiltrating macrophages. In contrast, no macrophages could be detected in corresponding hyperplastic tissue areas surrounding CIN‐II and CIN‐III lesions, although MCP‐1 was found to be highly expressed. Finally, in agreement with our earlier in vitro data, invasive carcinomas of the cervix uteri showed MCP‐1‐specific hybridization signals and macrophage infiltration only in the stroma surrounding the carcinoma cells and in endothelial cells of capillaries, especially at the invasion front of the tumor, while the inner mass of the carcinomas was completely negative. On the other hand, ISH and histochemical evaluation of inflammatory, non‐HPV‐associated cases of erosive endocervicitis indicate strong MCP‐1 expression, which is regularly accompanied by chemotactic appearance of macrophages. These observations indicate that dysregulation of MCP‐1‐gene expression may represent an important step during HPV‐linked carcinogenesis, allowing the escape of virus‐positive cells from local immune response. Int. J. Cancer 82:6–11, 1999.