Over-Expression of Topoisomerase II[alpha] is Related to the Grade of Cervical Intraepithelial Neoplasia (CIN) and High-Risk Human Papillomavirus (HPV), but does not Predict Prognosis in Cervical Cancer or HPV Clearance after Cone Treatment

Branca, Margherita, Giorgi, Colomba, Ciotti, Marco, Santini, Donatella, Di Bonito, Luigi, Costa, Silvano, Benedetto, Arrigo, Bonifacio, Daniela, Di Bonito, Paola, Paba, Pierpaulo, Accardi, Luisa, Mariani, Luciano, Ruutu, Merja, Syrjänen, Stina, Favalli, Cartesio and Syrjänen, Kari (2006) Over-Expression of Topoisomerase II[alpha] is Related to the Grade of Cervical Intraepithelial Neoplasia (CIN) and High-Risk Human Papillomavirus (HPV), but does not Predict Prognosis in Cervical Cancer or HPV Clearance after Cone Treatment. International Journal of Gynecological Pathology, 25 4: 383-392. doi:10.1097/01.pgp.0000209573.54457.32


Author Branca, Margherita
Giorgi, Colomba
Ciotti, Marco
Santini, Donatella
Di Bonito, Luigi
Costa, Silvano
Benedetto, Arrigo
Bonifacio, Daniela
Di Bonito, Paola
Paba, Pierpaulo
Accardi, Luisa
Mariani, Luciano
Ruutu, Merja
Syrjänen, Stina
Favalli, Cartesio
Syrjänen, Kari
Title Over-Expression of Topoisomerase II[alpha] is Related to the Grade of Cervical Intraepithelial Neoplasia (CIN) and High-Risk Human Papillomavirus (HPV), but does not Predict Prognosis in Cervical Cancer or HPV Clearance after Cone Treatment
Journal name International Journal of Gynecological Pathology   Check publisher's open access policy
ISSN 0277-1691
1538-7151
Publication date 2006-10-01
Year available 2006
Sub-type Article (original research)
DOI 10.1097/01.pgp.0000209573.54457.32
Open Access Status
Volume 25
Issue 4
Start page 383
End page 392
Total pages 10
Editor Mark H. Stoler
Place of publication Hagerstown, Maryland
Publisher Lippincott Williams & Wilkins
Language eng
Subject 111203 Cancer Genetics
Formatted abstract
Objective: One of the pathways leading to cervical cancer is a loss of normal cell cycle control. Topoisomerase II[alpha] and II[beta] are important nuclear proteins controlling the G2/M checkpoint, and shown to be over-expressed in many human cancers. Their links to oncogenic human papillomavirus (HPV) types and their prognostic value in cervical cancer are practically unexplored.

Material and Methods: As part of our HPV-PathogenISS study, a series of 150 squamous cell carcinomas (SCC) and 152 CIN lesions were examined using immunohistochemical (IHC) staining for topoisomerase II[alpha] (topo II[alpha]), and tested for HPV using PCR with three primer sets (MY09/11, GP5+/GP6+, SPF). Follow-up data were available from all SCC patients, and 67 CIN lesions had been monitored with serial PCR for HPV clearance/persistence after cone treatment.

Results: Topo II[alpha] expression increased with increasing grade of CIN (p = 0.0001), with the most dramatic up-regulation upon progression from CIN2 to CIN3 and peaking in SCC (OR 16.23; 95%CI 7.89-33.38). Topo II[alpha] up-regulation was also significantly associated with HR-HPV detection in univariate analysis (OR = 3.07; 95%CI 1.70-5.52), but was confounded by the histological grade (Mantel-Haenszel common OR = 1.622; 95%CI 0.782-3.365), and by entering both p16INK4a ( 9) and Survivin ( 33) in the multivariate regression model. Topo II[alpha] did not predict clearance/persistence of HR-HPV after treatment of CIN, and it was not a prognostic factor in cervical cancer in either univariate or multivariate analysis.

Conclusions: Over-expression of topo II[alpha] is significantly associated with progression from CIN2 to CIN3, being a late marker of cell proliferation. Its close association with HR-HPV is plausibly explained by the fact that E7 oncoproteins of these HR-HPV (but not LR-HPV) block the normal pRb-mediated inhibition of topo II[alpha] by degrading the wild-type Rb.

(C) 2006 International Society of Gynecological Pathologists

Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
UQ Diamantina Institute Publications
 
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Created: Sat, 06 Jun 2009, 00:06:35 EST by Mary-Anne Marrington on behalf of UQ Diamantina Institute