The integration of HR-HPV increases the expression of cyclins A and E in cytologies with and without low-grade lesions
MI Zubillaga-Guerrero1, B Illades-Aguiar2, MA Leyva-Vazquez2, E Flores-Alfaro3, E Castañeda-Saucedo4, JF Muñoz-Valle5, LC Alarcón-Romero1
1 Laboratory for Research in Cytopathology and Histoquemical, Academic Unit for Chemical Biological Sciences, Autonomous University of Guerrero, Chilpancingo, Guerrero, Mexico
2 Laboratory for Molecular Biomedicine, Academic Unit for Chemical Biological Sciences, Autonomous University of Guerrero, Chilpancingo, Guerrero, Mexico
3 Laboratory for Chronic-Degenerative Diseases, Academic Unit for Chemical Biological Sciences, Autonomous University of Guerrero, Chilpancingo, Guerrero, Mexico
4 Laboratory for Cancer Cellular Biology, Academic Unit for Chemical Biological Sciences, Autonomous University of Guerrero, Chilpancingo, Guerrero, Mexico
5 Department of Molecular Biology and Genomics, University Center for Health Sciences (CUCS), University of Guadalajara, Jalisco, Mexico
L C Alarcón-Romero
Avenue Lázaro Cárdenas, University City, Chilpancingo, Guerrero
Source of Support: Mixed Fund CONACYT-State Government of Guerrero. Convocation 2008-2 and Former Grantees Reincorporation Program PROMEP/SEP.UAGRO-106-2007-2010.,, Conflict of Interest: None
Background: Cyclin-A and cyclin-E are regulators of G1-S phase of normal cell cycle. Integration of human papilloma virus high-risk (HR-HPV) could alter this mechanism, and its overexpression has been associated with poor prognosis in cervical cancer.
Aim: To determine the expression of cyclin-A and cyclin-E, types of HR-HPV and physical state of DNA in cytologies with the diagnosis of low-grade squamous intraepithelial lesion (LSIL).
Materials and Methods: 115 cytological specimens in liquid base (liquid-PREP™ ) were analyzed. 25 specimens were with no signs of SIL (NSIL) and without HPV; 30 with NSIL with low-risk HPV (LR-HPV); 30 with NSIL with HR-HPV; and 30 with both LSIL and HR-HPV. The expression of cyclins was evaluated by immunocytochemistry; and the detection of viral DNA was done by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLPs) for genotyping or sequencing of HPV. The physical state of HPV was evaluated by in situ hybridization with amplification with tyramide.
Results: In the cytologies NSIL with LR-HPV, the expression of cyclin-A and cyclin-E was found respectively in 23.3% and 33.3% of the specimens. Among the specimens of NSIL with HR-HPV, 33.3% expressed cyclin-A and 40% cyclin-E, while 100% of the LSILs expressed the 2 cyclins. On the other hand, 100% of the samples NSIL with LR-HPV presented an episomal pattern. Of the specimens of NSIL with HR-HPV, 56.6% exhibited an episomal pattern, 23.3% integrated and 20%, mixed. Among the LSILs, 90% were mixed and 10% integrated.
Conclusions: The cyclins A and E are present in the LSILs that occur predominantly in mixed state in the presence of HR-HPV.