title: Both cell proliferation and apoptosis increase with lesion grade in cervical neoplasia but do not correlate with human papillomavirus type.
abstract: Recent molecular studies suggest that the expression of high-risk but not low-risk human papillomavirus (HPV) oncoproteins E6 and E7 can significantly alter normal cell cycle regulation. The alterations in cell cycle regulation may be reflected by changes in the balance between cell growth and cell loss through apoptosis in cell populations expressing E6 and/or E7. We evaluated the kinetic indices of cell proliferation and apoptosis in a histopathological spectrum of cervical neoplasia and compared low-versus high-risk HPV-associated lesions. The cell proliferation index, as determined by detection of the nuclear antigen Ki67, increased with increasing lesion grade. Apoptotic cells were identified with terminal deoxynucleotidyl transferase-labeling of the 3'-hydroxyl ends of DNA nucleosomes. No apoptosis was observed in normal epithelium, and only occasional apoptotic cells were seen in low-grade lesions. However, there was a low but measurable apoptotic index in the higher grade lesions, which increased with lesion grade. There was no significant difference in the proliferative and apoptotic indices in similar grade lesions when stratified into low-versus high-risk HPV types. These findings suggest that apoptosis in HPV-infected lesions correlates with proliferative activity rather than HPV type.
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: C
authors.initials: C
authors.lastname: Isacson
authors.forename: T D
authors.initials: TD
authors.lastname: Kessis
authors.forename: L
authors.initials: L
authors.lastname: Hedrick
authors.forename: K R
authors.initials: KR
authors.lastname: Cho
mesh_terms: D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000821:virology; D002453:Cell Cycle; D002455:Cell Division; D002584:Cervix Uteri / Q000166:cytology / Q000473:pathology / Q000821:virology; D003218:Condylomata Acuminata / Q000473:pathology / Q000821:virology; D004253:DNA Nucleotidylexotransferase / Q000032:analysis; D004847:Epithelial Cells; D004848:Epithelium / Q000473:pathology / Q000821:virology; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen; D007700:Kinetics; D009363:Neoplasm Proteins / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis; D009856:Oncogene Proteins, Viral / Q000032:analysis / Q000096:biosynthesis; D027383:Papillomaviridae / Q000302:isolation & purification*; D002583:Uterine Cervical Neoplasms / Q000473:pathology* / Q000821:virology*
chemical_list: D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D004253:DNA Nucleotidylexotransferase