Apoptosis-related proteins and cervical intraepithelial neoplasia in human immunodeficiency virus-seropositive women.
OBJECTIVE
To evaluate the expression of bcl-2, p-53, Ki-67, and apoptosis as evidenced by nuclear DNA fragmentation in cervical biopsies obtained from human immunodeficiency virus (HIV)-seropositive and HIV-seronegative women with a history of intravenous drug abuse.


METHODS
We investigated 109 consecutive cervical biopsies (73 from HIV seropositive and 36 from HIV seronegative patients), including 86 cervical intraepithelial neoplasia (CIN) lesions and 23 normal cervical epithelium. The markers of apoptosis and proliferation were detected using immunostaining methods on paraffin sections. The associations between HIV status and the intensities of immunostaining were tested by univariate and multivariable methods.


RESULTS
The severity of CIN correlated directly with the intensities of p-53 (Spearman Rho = 0.19; P = 0.05) and Ki-67 immunostaining (Spearman Rho = 0.46, P < 0.001) and with apoptosis and Bcl-2 expression (chi-square for trend = 10.6 and 3.91 , P < 0.001 and P = 0.048, respectively).After adjustment, by logistic regression analysis, for the potential confounding effect of severity of CIN and Human Papillomavirus (HPV) infection, apoptosis was five times more common in cervical biopsies of HIV seropositive compared to HIV seronegative patients (27 out of 73 as compared to 4 out of 36, adjusted Odds Ratio = 5.0; 95% confidence intervals = 1.56-16.33, P = 0.007). The adjusted odds ratio of increasing p53 immunodetection was significantly higher in biopsies obtained from HIV-seropositive patients compared to HIV seronegative controls (OR = 8.7; 95% confidence intervals = 2.97-25.3, P < 0.0001).


CONCLUSIONS
Markers of apoptosis such as nuclear DNA fragmentation and p-53 immunoreactivity are more intensely expressed in cervical biopsies of normal and dysplastic epithelium of HIV-seropositive compared to HIV-seronegative women.
Spinillo
Arsenio
A
Department of Obstetrics and Gynecology, IRCCS Policlinico S. Matteo, University of Pavia, Piazzale Golgi 2, 27100 Pavia, Italy. spinillo@smatteo.pv.it
Zara
Francesca
F
Zappatore
Rita
R
Cesari
Stefania
S
Bergante
Carola
C
Morbini
Patrizia
P
D017209:Apoptosis / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006678:HIV / Q000235:genetics; D006679:HIV Seropositivity / Q000150:complications* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D019562:Viral Load; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000821:virology*
D004279:DNA, Viral; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53