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.
Fujimura
H
H
Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Nagoya, Japan.
Ino
K
K
Nagasaka
T
T
Nakashima
N
N
Nakazato
H
H
Kikkawa
F
F
Mizutani
S
S
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
D000626:Aminopeptidases; D043384:Glutamyl Aminopeptidase