title: The association of vascular proliferation with HPV status and epithelial PCNA positivity in cervical intraepithelial lesions.
abstract: In this study we investigated the number of blood vessels and vascular proliferation in subepithelial areas of 80 cervical condylomas and cervical intraepithelial neoplasias (CIN). The number of blood vessels was determined by counting factor VIIIRAg-positive vascular channels in areas beneath the epithelial lesions. Vascular proliferation was evaluated by determining the number of proliferating cell nuclear antigen (PCNA)-positive endothelial cells in the subepithelial connective tissues. The results were compared with the expression of human papillomavirus (HPV) DNA subgroups (6/11 (low-risk) and 16/18/31/33/35 (high-risk) of the lesions, as determined by dot-blot and in situ hybridization, and with epithelial cell proliferation as determined by immunohistochemistry for PCNA. Also p53 immunohistochemistry of the lesions was performed. Even though CIN II-III lesions on average contained more factor VIIIRAg-positive blood vessels compared to condylomas and CIN I lesions, no significant association was found between their number and the degree of dysplasia. However, moderate or strong PCNA staining in vascular endothelial cells was seen significantly more often in CIN II-III lesions than in condylomas and CIN I lesions (p = 0.008): 34/80 (45%) cases contained detectable HPV DNA as determined by dot-blot or in situ hybridization. There was no correlation between the presence or absence of HPV DNA and the number of PCNA-positive endothelial cells. Nine cases showed p53-positive cell nuclei and in three cases there was more than 1% positive nuclei in the lesion. No association was found between the vascularity or the number of PCNA-positive endothelial cells and the p53 immunoreactivity. The increased proliferative activity of endothelial cells in CIN II-III lesions suggests that they are angiogenically more active than condylomas and CIN I lesions. This activity does not, however, depend on the HPV or p53 status. This is the first report in which endothelial cell PCNA positivity was used as a marker for vascular proliferation.
authors.affiliation: Department of Pathology, University of Oulu, Finland.
authors.forename: Y
authors.initials: Y
authors.lastname: Soini
authors.forename: R
authors.initials: R
authors.lastname: Pöllänen
authors.forename: S
authors.initials: S
authors.lastname: Kemppainen
authors.forename: P
authors.initials: P
authors.lastname: Pääkkö
authors.forename: V P
authors.initials: VP
authors.lastname: Lehto
mesh_terms: D000951:Antigens, Neoplasm / Q000032:analysis*; D015415:Biomarkers; D002455:Cell Division; D003218:Condylomata Acuminata / Q000378:metabolism / Q000821:virology; D015344:DNA Probes, HPV; D004279:DNA, Viral / Q000302:isolation & purification; D004730:Endothelium, Vascular / Q000737:chemistry; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins / Q000032:analysis; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000821:virology; D009687:Nuclear Proteins / Q000032:analysis; D027383:Papillomaviridae / Q000145:classification / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000378:metabolism / Q000821:virology*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D014412:Tumor Virus Infections / Q000378:metabolism / Q000821:virology*; D002583:Uterine Cervical Neoplasms / Q000098:blood supply* / Q000737:chemistry / Q000821:virology; D002575:Uterine Cervicitis / Q000378:metabolism / Q000821:virology; D014841:von Willebrand Factor / Q000032:analysis; D002578:Uterine Cervical Dysplasia / Q000098:blood supply* / Q000737:chemistry / Q000821:virology
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D015344:DNA Probes, HPV; D004279:DNA, Viral; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; D014841:von Willebrand Factor