Cell-cycle and suppressor proteins expression in uterine cervix in HIV/HPV co-infection: comparative study by tissue micro-array (TMA).
BACKGROUND
The oncoproteins of human papillomavirus (HPVs) directly effect cell-cycle control. We hypothesize that regulatory and cell cycle protein expression might be additionally modified in the cervix of HIV/HPV co-infected women.


METHODS
We analyzed the expression of Rb, p27, VEGF and Elf-1 transcriptor factor by immunohistochemistry in 163 paraffin-embeded cervical samples using Tissue Micro-Array (TMA) and correlated this to HIV-1 and HPV infection.


RESULTS
HIV/HPV co-infection was associated with a significant increase in expression (p < 0.001) of VEGF and p27 in both low and high grade CIN when compared to the cervices of women infected by HPV alone. Decreased Rb expression was evident with increased CIN grade in the cervices of women infected with HPV alone (p = 0.003 average of cells/mm2 in CIN I: 17.9, CIN II/III: 4.8, and tumor 3.9). Rb expression increased 3-fold for both low and high grade CIN with HPV/HIV-1 co-infection compared to HPV infection alone but did not reach statistical significance. There was a significant increase in Elf-1 expression in HPV+/HIV- women with CIN II/III and tumor (average of cells/mm2 in CIN I: 63.8; CIN II/III: 115.7 and tumor: 112.0, p = 0.005), in comparison to controls.


CONCLUSIONS
Co-infection of HPV and HIV leads to significant increase in the VEGF and p27 expression when compared to HPV+/HIV-negative infection that could facilitate viral persistence and invasive tumor development.
Nicol
Alcina F
AF
Laboratory of Immunopathology, Instituto Oswaldo Cruz - FIOCRUZ, Rio de Janeiro, Brazil. nicol@ioc.fiocruz.br
Pires
Andréa Rodrigues Cordovil
AR
de Souza
Simone R
SR
Nuovo
Gerard J
GJ
Grinsztejn
Beatriz
B
Tristão
Aparecida
A
Russomano
Fabio B
FB
Velasque
Luciane
L
Lapa e Silva
José R
JR
Pirmez
Claude
C
D018791:CD4 Lymphocyte Count; D002584:Cervix Uteri / Q000378:metabolism* / Q000473:pathology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D052162:Human papillomavirus 16; D052161:Human papillomavirus 18; D006801:Humans; D007150:Immunohistochemistry; D009687:Nuclear Proteins / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D016160:Retinoblastoma Protein / Q000378:metabolism*; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D002578:Uterine Cervical Dysplasia / Q000378:metabolism / Q000473:pathology
C512897:ELF1 protein, human; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D050760:Cyclin-Dependent Kinase Inhibitor p27