Aberrant connexin 43 and 26 expression in cervical dysplasia.

Abstract

Objective: To determine whether connexin (Cx) expression is altered in cervical dysplasia.

Study design: Cx proteins form gap junctions and are expressed in squamous epithelia including ectocervix. We used multispectral imaging to perform a quantitative immunohistochemical survey of Cx43 Cx26 in 37 archival human cervical specimens.

Results: Cx43 expression was very low in normal cervix (100%), but was increased in low-grade squamous intraepithelial lesions (LSILs) (64%), primarily in a parabasal distribution. High-grade squamous intraepithelial lesions (HSILs) showed weak full-thickness Cx43 staining (53%) or lacked Cx43 (47%). An aberrant increase in Cx43 expression was often (62%) present in histologically normal areas of specimens that elsewhere harbored dysplasia. Cx26 was highly expressed in the basal layer of normal ectocervix (100%). In LSIL, 57% showed a decrease in Cx26 and the rest showed no change relative to the normal pattern. In HSIL, Cx26 was expressed in the full thickness of the epithelium, at a high level in 80% of cases and a low level in the rest.

Conclusion: Cx alteration is moderately consistent in cervical dysplasia, and for Cx43 can precede histologic changes. The resulting changes in Cx signaling may be important in the pathogenesis of cervical intraepithelial neoplasia.