Relevance of the rates of PCNA, Ki-67 and p53 expression according to the epithelial compartment in cervical lesions.
In order to assess further biological evidence for similarities among the "diagnostic classes" of cervical lesions, which are now a matter of international discussion in the search for a uniform classification, the purpose of this study was to characterize the immunoexpression of cell proliferation markers (proliferating cell nuclear antigen, PCNA and Ki-67) and protein p53. Each marker was individually quantified in basal, intermediate, and superficial epithelial compartments presenting chronic cervicitis (CC) accompanied by the cytopathic effects of infection by human papillomavirus (CCHPV) or not (CC), as well as in cervical intraepithelial neoplasia (CIN) grades I, II, and III. A total of 100 patients were evaluated and the positive nuclei were counted separately, including all extensions of the available epithelium. The percentage of PCNA- and Ki-67-positive cells increased with increasing grade of the cervical lesions, although PCNA immunoreactivity was always greater than the immunoreactivity observed with Ki-67 antigen. The immunoexpression of p53 protein was found to be weak, with no remarkable behavior in any specific "diagnostic class". The differences in cell proliferation markers found herein further emphasize the progressive loss of epithelial layer organization in the course of the development of preneoplastic changes in cervical squamous epithelium. Furthermore, difficulties in morphologically distinguishing "borderline lesions" persist when cell cycle markers are studied, further supporting the suggestion to consider the lesions of CCHPV and CIN I together as only one diagnostic class. Conversely, the different immune profile found between CIN II and III further supports the validity of the subdivision of CIN into three groups.
Maeda
M Y
MY
Division of Pathology, Institute Adolfo Lutz, Av. Dr Arnaldo, 355, 01246-902 São Paulo, Brasil. mysmaeda@ial.sp.gov.br
Simões
M
M
Wakamatsu
A
A
Longatto Filho
A L
AL
Oyafuso
M
M
de Mello
E S
ES
Otta
M M
MM
Alves
V A
VA
D014408:Biomarkers, Tumor; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D002467:Cell Nucleus / Q000737:chemistry; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D002908:Chronic Disease; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis* / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis* / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D014412:Tumor Virus Infections / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002577:Uterine Cervical Diseases / Q000145:classification / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000145:classification / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002575:Uterine Cervicitis / Q000378:metabolism / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000145:classification / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53