Differential expression of human Dlg in cervical intraepithelial neoplasias.

Objectives: To evaluate the potential role of human discs large (hDlg) protein in the pathogenesis of cervical neoplasia by examining the changes of hDlg protein expression in normal cervical epithelium as well as various stages of cervical dysplasia.

Materials And Method: Archived formalin-fixed, paraffin-embedded cervical tissue sections with known status of human Papillomavirus (HPV) infection were examined for hDlg expression using immunohistochemical staining by a monoclonal antibody generated against hDlg. The specimens include normal epithelium, low-grade and high-grade squamous intraepithelial lesions, and squamous cell carcinoma.

Results: The hDlg protein localized primarily in the basolateral membrane of glandular columnar cells in normal endocervical epithelium. In the squamous epithelium, the hDlg staining is strong in the basal and parabasal layers and rapidly fades away in the superficial layers. Although predominantly membrane-associated, some cytoplasmic staining of hDlg is also detectable that decreases in intensity from basal to superficial layers. In low-grade squamous intraepithelial lesion, there is a moderate increase in the membranous as well as cytoplasmic staining of hDlg in the cells of superficial layer and a modest loss of membranous staining of hDlg in the basal layer. This "reverse staining pattern" for hDlg is more prominent and constant feature of high-grade squamous intraepithelial lesions. The changes of the hDlg expression are, however, invariable regardless the subtypes of HPV infection of the specimens. In the invasive squamous cell carcinoma, membranous staining of hDlg is reduced or absent with some mitotic cells showing evidence of hDlg accumulation in the midbody zone.

Conclusions: These data suggest a functional role of hDlg in the development and progression of cervical neoplasia with implications in cytokinesis, viral trafficking, and metastasis pathways.