Co-expression of p53 and Bcl-2 proteins in human papillomavirus-induced premalignant lesions of the uterine cervix: correlation with progression to malignancy.
OBJECTIVE
To analyze aberrant expression of the apoptotic protein p53 and the anti-apoptotic protein Bcl-2 in premalignant lesions of the uterine cervix induced by human papillomavirus (HPV) infection and its significance for early diagnosis of cervical cancer.


METHODS
Cytological adequate smears (n = 382) from various grades of squamous intraepithelial lesions (SILs; n = 142), 'atypical squamous cells of unknown significance' (ASCUS; n = 128) and normal tissue (n = 112) were investigated immunocytochemically for aberrant expression of p53 and Bcl-2 proteins using the streptavidin-biotin-peroxidase method; HPV status was analyzed in cervical smears using general and type-specific primers.


RESULTS
HPV-DNA of any type was detected in 25.7% (98/382) of cases. HPV16 was seen in 58.2% (57/98), HPV18 in 20.4% (20/98) and other HPV types in 21.4% (21/98). Abnormal nuclear expression of p53 protein and cytoplasmic expression of Bcl-2 protein were noted in cervical dysplasia and an association with the presence of HPV16/HPV18 was noted. The intensity of immunoreactivity for p53 and Bcl-2 proteins varied between different cytological grades of cervical smears. Follow-up data revealed that cases with high-risk HPV and co-induced expression of apoptosis-regulatory proteins presented a trend to progressive disease.


CONCLUSIONS
The detection of both p53 and Bcl-2 proteins in cervical smears can be used as independent diagnostic marker for early-stage HPV-associated cervical cancer.
Singh
Madhulika
M
Proteomics Laboratory, Indian Institute of Toxicology Research, Lucknow, India.
Srivastava
Smita
S
Singh
Uma
U
Mathur
Neeraj
N
Shukla
Yogeshwer
Y
D052685:Alphapapillomavirus / Q000145:classification / Q000235:genetics / Q000502:physiology; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D003581:Cytodiagnosis; D004279:DNA, Viral / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D054884:Host-Pathogen Interactions; D006801:Humans; D007150:Immunohistochemistry; D030361:Papillomavirus Infections / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology; D014626:Vaginal Smears
D014408:Biomarkers, Tumor; D004279:DNA, Viral; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53