PMID- 14694518
OWN - NLM
STAT- MEDLINE
DCOM- 20040209
LR  - 20221207
IS  - 0022-3417 (Print)
IS  - 0022-3417 (Linking)
VI  - 202
IP  - 1
DP  - 2004 Jan
TI  - Transition of high-grade cervical intraepithelial neoplasia to micro-invasive 
      carcinoma is characterized by integration of HPV 16/18 and numerical chromosome 
      abnormalities.
PG  - 23-33
AB  - Cervical intraepithelial neoplasia (CIN I, II, and III) and cases of CIN III 
      associated with micro-invasive cervical carcinoma (CIN III & mCA) were analysed 
      for evidence of episomal or integrated human papillomavirus (HPV) 16/18 DNA by 
      fluorescence in situ hybridization (FISH). In parallel, numerical aberrations of 
      chromosomes 1, 17, and X were determined in these lesions as indicators of 
      genomic instability. HPV 16/18 DNA was present in 2 of 12 CIN I, 19 of 23 CIN 
      II/III, and 10 of 12 CIN III & mCA. None of the CIN I and only two of the 19 HPV 
      16/18-positive solitary CIN II/III showed an integrated HPV pattern. However, all 
      ten cases of HPV-positive CIN III & mCA showed this pattern. Transition of CIN 
      II/III to CIN III & mCA therefore correlates strongly with viral integration 
      (p<0.001). Chromosomal aberrations were detected in 23 of 31 HPV 16/18-positive 
      lesions (14 solitary CIN I-III and nine CIN III & mCA) and 5 of 16 HPV-negative 
      lesions. Nine of 21 HPV 16/18-positive solitary CIN I-III showed tetrasomy for 
      all chromosomes tested, while trisomies for a single chromosome were seen in a 
      further five of these HPV-positive lesions. In eight of ten HPV-positive CIN III 
      & mCA, predominantly aneusomies and/or polysomies were detected. A significant 
      correlation (p<0.02) was found between the chromosome copy number and the 
      physical status of HPV, indicating that in its episomal form HPV induces genomic 
      changes such as tetrasomies and single trisomies, while HPV integration 
      correlates with aneusomies and polysomies, predominantly detected in CIN III & 
      mCA. These data indicate that integration of HPV 16/18 DNA is a pivotal step in 
      the transition of CIN to micro-invasive carcinoma.
CI  - Copyright 2004 John Wiley & Sons, Ltd.
FAU - Hopman, Anton H N
AU  - Hopman AH
AD  - Department of Molecular Cell Biology, Research Institute Growth and Development 
      (GROW), University of Maastricht, The Netherlands. hopman@molcelb.unimaas.nl
FAU - Smedts, Frank
AU  - Smedts F
FAU - Dignef, Wendy
AU  - Dignef W
FAU - Ummelen, Monique
AU  - Ummelen M
FAU - Sonke, Gabe
AU  - Sonke G
FAU - Mravunac, Marcel
AU  - Mravunac M
FAU - Vooijs, G Peter
AU  - Vooijs GP
FAU - Speel, Ernst-Jan M
AU  - Speel EJ
FAU - Ramaekers, Frans C S
AU  - Ramaekers FC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
RN  - 0 (DNA Probes, HPV)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (DNA, Viral)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Cell Transformation, Neoplastic/*pathology
MH  - *Chromosome Aberrations
MH  - Chromosomes, Human, Pair 1/genetics
MH  - Chromosomes, Human, Pair 17/genetics
MH  - Chromosomes, Human, X/genetics
MH  - DNA Probes, HPV
MH  - DNA, Neoplasm/analysis
MH  - DNA, Viral/*analysis
MH  - Female
MH  - Humans
MH  - Immunohistochemistry/methods
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Middle Aged
MH  - Papillomaviridae/*genetics
MH  - Papillomavirus Infections/genetics/pathology
MH  - Plasmids/genetics
MH  - Uterine Cervical Neoplasms/*genetics/pathology
MH  - Virus Integration
MH  - Uterine Cervical Dysplasia/*genetics/pathology
EDAT- 2003/12/25 05:00
MHDA- 2004/02/11 05:00
CRDT- 2003/12/25 05:00
PHST- 2003/12/25 05:00 [pubmed]
PHST- 2004/02/11 05:00 [medline]
PHST- 2003/12/25 05:00 [entrez]
AID - 10.1002/path.1490 [doi]
PST - ppublish
SO  - J Pathol. 2004 Jan;202(1):23-33. doi: 10.1002/path.1490.