Human papillomavirus infection, centrosome aberration, and genetic stability in cervical lesions.
DNA replication and centrosome duplication have to be strictly synchronized to guarantee genomic stability. p53, pRb, cyclin E, and cyclin A are reported to be involved in the synchronizing process. We investigated the relationship between papillomavirus infection, centrosome aberration and aneuploidy during genesis of cervical carcinoma. The number of centrosomes found in cells from normal cervical epithelium (n = 5), condyloma acuminata (n = 5), cervical intraepithelial neoplasia (CIN) I, II, and III (n = 14) and invasive cervical carcinoma (n = 5) was analyzed by gamma tubulin immunofluorescence staining. The nuclear DNA content was investigated by image cytometry and human papillomavirus (HPV) infection was determined by polymerase chain reaction. Normal epithelia and condyloma acuminata showed cells with one or two centrosomes, whereas CIN lesions showed cells with an increasing number of centrosomes. This abnormality was found to be lowest in CIN I lesions, increased with advancing grade of CIN and was highest in lesions of invasive carcinomas. In parallel, an increasing number of cells with aberrant DNA content was seen. All carcinomas and all except one of the CIN III lesions showed aneuploidy. Three CIN II cases were aneuploid and two cases with CIN I were tetraploid. Normal epithelia and condyloma acuminata showed diploidy. All invasive carcinomas and lesions with CIN were positive for high-risk HPV types 16, 18, or 31, except one invasive carcinoma and one CIN II lesion positive for universal primers only. Three condyloma acuminata were HPV 16-positive and one HPV 6-positive. The results suggest that high-risk HPV infection is correlated to a progressive numerical disturbance of centrosome replication followed by progressive chromosomal aberrations in CIN lesions and invasive carcinomas.
Skyldberg
B
B
Division of Cellular and Molecular Tumor Pathology, Cancer Center Karolinska, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden. Skyldberg@impi.ki.se
Fujioka
K
K
Hellström
A C
AC
Sylvén
L
L
Moberger
B
B
Auer
G
G
D000328:Adult; D000368:Aged; D000782:Aneuploidy; D018385:Centrosome; D003218:Condylomata Acuminata / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology; D004273:DNA, Neoplasm / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D019044:Image Cytometry; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000473:pathology / Q000821:virology*; D016133:Polymerase Chain Reaction; D014404:Tubulin / Q000032:analysis; D014412:Tumor Virus Infections / Q000473:pathology / Q000821:virology*; D002583:Uterine Cervical Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000821:virology*
D004273:DNA, Neoplasm; D004279:DNA, Viral; D014404:Tubulin