Nectin-1 Expression in the Normal and Neoplastic Human Uterine Cervix

Abstract

Nectin-1 is an immunoglobulin-like adhesion molecule that is widely expressed in epithelial tissues and participates in the formation of adherens junctions. Reduced expression of nectin-1 has been reported in invasive carcinomas of the human skin. To determine the pattern of nectin-1 expression in the normal, dysplastic, and neoplastic human uterine cervix. This retrospective study was performed using immunohistochemistry of specimens of normal mucosa (n = 18) and preneoplastic and neoplastic conditions of the human uterine cervix including squamous dysplasia and invasive uterine cervical squamous carcinoma (n = 23). All specimens were graded according to intensity of cytoplasmic staining (0 = no staining; 4 = strongest intensity). Strong widespread cytoplasmic nectin-1 reactivity was found in normal uterine cervical squamous and endocervical mucosa (mean grade = 2.63). In contrast, uterine cervical and endocervical stroma showed minimal to absent staining (mean grade = 0.58). There was a significant difference in staining intensity between normal mucosa versus stroma (P < .001, Wilcoxon matched pairs- signed ranks test). All squamous dysplasia and carcinoma specimens displayed strong cytoplasmic nectin-1 staining (mean grade = 3.08). The advancing edge of these carcinomas demonstrated significantly decreased or absent expression of nectin-1 (mean grade = 1.39) with significant difference in staining intensity at the center of invasive tumors versus the advancing edge (P = .004, Wilcoxon matched pairs-signed ranks test). Normal squamous mucosa, dysplasia, and invasive carcinomas of the human uterine cervix stain strongly with nectin-1, and this staining is reduced or absent in the advancing edge of invasive tumors. These findings suggest that down-regulation of nectin-1 may be associated with the loss of cell-to-cell adhesion at the advancing edge of invasive squamous carcinomas of the human uterine cervix.