Evaluation of expression of apoptosis-related proteins and their correlation with HPV, telomerase activity, and apoptotic index in cervical cancer.
OBJECTIVE
The aim of this study was to examine the expression of apoptosis-related proteins in cervical cancer, and investigate their correlation with the apoptotic index (AI), telomerase activity, human papilloma virus (HPV) infection and clinicopathological characteristics.


METHODS
Fifty cervical cancer samples and 20 normal cervical tissues were assessed for the protein expression of survivin, Bcl-2, Cox-2, p53 and p73 by immunohistochemistry. HPV DNA was detected by PCR, telomerase activity by PCR-ELISA, and AI by TUNEL assay.


RESULTS
46/50 cervical tumors (92%) showed an increased telomerase activity as compared to 3/20 (15%) controls. 45/50 (90%) cervical tumors were positive for HPV, of which 30 were HPV-16 positive and 5 were HPV-18 positive. 24/50 (48%) tumors were positive for survivin, 14 (28%) for Bcl-2, 13 (26%) for Cox-2, 19/45 (42%) for p73, 10/45 (24%) for p53. Telomerase activity was highest in tumors with the poorest grade. A positive correlation was seen between survivin and Bcl-2, survivin and tumor stage, Bcl-2 and Cox-2, p73 and p53 and p73 and the AI. Despite the overexpression of various antiapoptotic proteins, no significant difference was observed in the AI between tumors and controls.


CONCLUSIONS
Since deregulation of the apoptotic pathway appears to occur in cervical cancer, some apoptosis-related proteins could be assessed as potential markers for progression/prognosis in cervical cancer. Additionally, newer proteins such as p73 may play a compensatory role for the nonfunctional proteins such as p53.
Singh
A
A
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi-110029, India.
Sharma
H
H
Salhan
S
S
Gupta
S Datta
SD
Bhatla
N
N
Jain
S K
SK
Singh
N
N
D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D051546:Cyclooxygenase 2; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051034:Inhibitor of Apoptosis Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D008875:Middle Aged; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000096:biosynthesis; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications*; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D000077022:Survivin; D019098:Telomerase / Q000378:metabolism*; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D025521:Tumor Suppressor Proteins; D014412:Tumor Virus Infections / Q000150:complications*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000821:virology
C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D051034:Inhibitor of Apoptosis Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D019098:Telomerase