Aminopeptidase A expression in cervical neoplasia and its relationship to neoplastic transformation and progression.

Aminopeptidase A (AP-A) is a cell surface metallopeptidase which specifically cleaves the amino-terminal acidic residue from peptide substrates such as angiotensin II. AP-A is identical to the differentiation-related antigen, murine BP-1 or human kidney gp160, and is involved in regulating cell differentiation and/or neoplastic transformation of certain normal and transformed cells. We examined expression of AP-A in premalignant and malignant lesions of the uterine cervix, and investigated whether its expression was related to disease progression and neoplastic transformation. Formalin-fixed, paraffin-embedded tissue sections including 14 cervical intraepithelial neoplasms (CIN) and 23 invasive squamous cell carcinomas (SCC) were immunohistochemically evaluated. AP-A was localized in the basal cell layer in normal squamous epithelium. In CIN, AP-A expression was found on dysplastic cells, and increased with the severity of the precancerous lesions. In invasive cancer, 18 of 19 non-keratinizing-type SCCs and none of 4 keratinizing-type SCCs expressed AP-A. In addition, AP-A immunoreactivity was significantly correlated with proliferating cell nuclear antigen expression in both CIN and SCC cases. Furthermore, angiotensin II type 1 receptor was present in all AP-A-positive SCCs. These results indicate that AP-A is upregulated as the lesion progresses toward carcinoma in the cervical epithelium, and suggest that AP-A may play a regulatory role in neoplastic transformation and disease progression in cervical neoplasms and may serve as a potential tumor marker during cervical neoplasia development.