title: Effect of human papillomavirus on cell cycle-related proteins p16, Ki-67, Cyclin D1, p53, and ProEx C in precursor lesions of cervical carcinoma: a tissue microarray study.
abstract: In-depth study of cell cycle proteins and human papillomavirus (HPV) genotyping can provide useful information about the malignant potential of precursor lesions of cervical carcinoma (CC). Immunostaining of cell cycle-related proteins (p16, cyclin D1, Ki-67, p53, and ProEx C) was evaluated using tissue microarrays, and HPV genotypes were identified in 144 cervical tissue specimens encompassing normal or benign epithelial lesions, low- and high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively), and CC. In addition, 14 cases with atypical immature metaplasia (AIM) were included to compare their immunohistochemical features with those of well-established precursor lesions. Expression of p16, Ki-67, and ProEx C was most associated with the severity of dysplasia. Positive expression of p16, Ki-67, and ProEx C and negative expression of p53 seem to be related to HPV-16 infection. AIM cases show an immunohistochemical pattern more similar to LSIL than to HSIL. Immunohistochemical assessment of cell cycle proteins may help to distinguish normal and benign conditions of the cervix from precursor lesions of CC.
authors.affiliation: Pharmacogenetic and Molecular Pathology Group, Santa María del Rosell University Hospital, 30203 Cartagena, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Conesa-Zamora
authors.forename: Asunción
authors.initials: A
authors.lastname: Doménech-Peris
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Orantes-Casado
authors.forename: Sebastián
authors.initials: S
authors.lastname: Ortiz-Reina
authors.forename: Laura
authors.initials: L
authors.lastname: Sahuquillo-Frías
authors.forename: Jesús
authors.initials: J
authors.lastname: Acosta-Ortega
authors.forename: José
authors.initials: J
authors.lastname: García-Solano
authors.forename: Miguel
authors.initials: M
authors.lastname: Pérez-Guillermo
mesh_terms: D000951:Antigens, Neoplasm / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D019938:Cyclin D1 / Q000096:biosynthesis; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D064111:Minichromosome Maintenance Complex Component 2; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009687:Nuclear Proteins / Q000096:biosynthesis; D030361:Papillomavirus Infections / Q000150:complications / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2; D004250:DNA Topoisomerases, Type II