title: Aminopeptidase A expression in cervical neoplasia and its relationship to neoplastic transformation and progression.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Fujimura
authors.forename: K
authors.initials: K
authors.lastname: Ino
authors.forename: T
authors.initials: T
authors.lastname: Nagasaka
authors.forename: N
authors.initials: N
authors.lastname: Nakashima
authors.forename: H
authors.initials: H
authors.lastname: Nakazato
authors.forename: F
authors.initials: F
authors.lastname: Kikkawa
authors.forename: S
authors.initials: S
authors.lastname: Mizutani
mesh_terms: D000328:Adult; D000368:Aged; D000626:Aminopeptidases / Q000032:analysis*; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002584:Cervix Uteri / Q000201:enzymology; D018450:Disease Progression; D004848:Epithelium / Q000201:enzymology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D043384:Glutamyl Aminopeptidase; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000201:enzymology* / Q000473:pathology
chemical_list: D000626:Aminopeptidases; D043384:Glutamyl Aminopeptidase