Characterization and functional analysis of the expression of vascular adhesion molecules in human papillomavirus-related disease of the cervix.

BACKGROUND

Cervical intraepithelial neoplasia (CIN) is associated with changes in local immune cell populations, although the role of vascular adhesion molecules in mediating such changes by controlling the traffic of mononuclear cells to the cervix has not been investigated previously.

METHODS

The authors used immunohistochemistry to examine the expression of three vascular adhesion molecules--ICAM-1, VCAM-1 and E-selectin--in the normal cervix and in biopsies of CIN Grade 1 (CIN-1) (low grade squamous intraepithelial lesions [LG-SIL]) and CIN-2/3 (high grade squamous intraepithelial lesions[HG-SIL]). In addition, the authors examined the functional role of these molecules by adapting the frozen section adhesion assay of Stamper and Woodruff to investigate in vitro the molecular basis of the interaction between cervical endothelial cells and activated T-lymphocytes.

RESULTS

Whereas there was no difference in adhesion molecule expression between normal cervix and CIN-1 (LG-SIL), all three molecules investigated were significantly up-regulated in CIN-2/3 (HG-SIL), an observation that correlated with an enhanced ability of stromal endothelial cells in CIN-2/3 (HG-SIL) biopsies to bind activated peripheral blood lymphocytes in vitro. Monoclonal antibodies blocking ICAM-1 function were able to reduce such adhesion significantly in three of three experiments, and antibodies blocking VCAM-1 produced a significant reduction in one of three experiments. No inhibition was seen with antibodies against E-selectin.

CONCLUSIONS

The enhanced expression of vascular adhesion molecules in CIN-2/3 (HG-SIL) appears to be functionally important in enabling the local recruitment of immunocompetent cells and supports the notion of a local antineoplastic immune response in high grade cervical intraepithelial lesions.