[Relationship among HPV16 infection and Expression of hTERT, p21waf1, Ki67 in cervical intraepithelial neoplasias and squamous cell carcinomas of cervix uteri].
BACKGROUND
To investigate the relationship among human papillomavirus (HPV)16 infection and the expression of telomerase catalytic protein subunit (hTERT), tumor suppressor gene p21waf1, proliferation antigen Ki67 in cervical intraepithelial neoplasias (CIN) and squamous cell carcinomas (SCC) of cervix uteri and their significance.


METHODS
Tissue microarray combined with in situ hybridization (ISH) and immunohistochemical staining (EliVision plus method) was used to detect the expression of HPV16 RNA, hTERT, Ki67 and p21waf1 proteins in the cervix uteri specimens from 130 subjects, including normal cervical tissue (n=26), CIN (n=46) and SCC (n=58).


RESULTS
(1) The positive rate of HPV16 hybridization signals and expression of hTERT, Ki67 in CINII-III, in situ carcinoma and invasive SCC were all significantly higher than in normal cervical tissue (P < 0.05 for all), and was also higher in SCC than in CIN (P < 0.05 for all). There was a significant difference among CIN I, II and III (P < 0.05 for all). (2) The positive expression of p21waf1 protein only in SCC was significantly lower than in normal cervical tissue (P < 0.05), but there was no significant differences among other groups (all P > 0.05). (3) The positive rate of HPV16 and the expression of Ki67 showed respectively positive being correlated with the expression of hTERT (P < 0.05, r=0.339; P < 0.05, r=0.398); HPV16, hTERT and Ki67 showed respectively negative correlation with the expression of p21waf1 (P < 0.05, r=-0.337; P < 0.05, r=-0.248; P < 0.05, r=-0.446); There was no significant relation between HPV16 and Ki67 (P > 0.05).


CONCLUSIONS
The results suggest that in tissues of CIN and SCC changes in hTERT, p21waf1 and Ki67 expression may be associated with HPV16 infection and they interact with each other, which can influent the progression of CIN and carcinogenesis of SCC. These biomarkers may be analyzed comprehensively to reveal the detailed mechanism by which HPV16 participate in malignant transformation and to provide some informations on the diagnosis of patients with high risk for malignant progression. Tissue microarray is an efficient platform for high-throughput analysis of genes and their expression products in investigations.
Zhao
Fu-xi
FX
Department of Medicine, Datong University, Datong 037008, China. DT2FX@163.com
Sun
Rui-fang
RF
Wang
Jin-fen
JF
Chen
Xiang-wei
XW
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D054884:Host-Pathogen Interactions; D052162:Human papillomavirus 16 / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D019394:Ki-67 Antigen / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics; D019098:Telomerase / Q000096:biosynthesis / Q000235:genetics; D046888:Tissue Array Analysis; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000378:metabolism / Q000821:virology*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019394:Ki-67 Antigen; D010446:Peptide Fragments; C514987:GV1001 peptide; D019098:Telomerase