Decreased expression of human papillomavirus E2 protein and transforming growth factor-beta1 in human cervical neoplasia as an early marker in carcinogenesis.
OBJECTIVE
Human papillomavirus (HPV) is thought to be one of the possible causative factors in cervical carcinogenesis, and cervical carcinoma cells are refractory to tumor transforming growth factor (TGF)-beta1. The purpose of this study is to investigate the possible cause-effect association between HPV and TGF-beta1 during cervical tumorigenesis.


METHODS
We assessed the expression of HPV capsid proteins, HPV-16 E7, HPV-16 E2 (C and N terminals), TGF-beta1, and their receptors TGF-beta RI and RII by immunohistochemistry in 48 paraffin-embedded blocks of tumor tissue derived from patients of cervical neoplasia.


RESULTS
Expression of TGF-beta1 decreased as tumor cells progressed from cervical intraepithelial neoplasia (CIN)1, CIN2, CIN3, to microinvasive carcinoma (P < 0.05). Levels of TGF-betaRI and TGFbeta-RII stayed the same in all cases. HPV was found in 89.6% of the studied sections, and cervical lesions without HPV infection expressed significantly less TGF-beta1 (P < 0.05). By comparing the expression pattern of TGF-beta1 and HPV in the neoplastic cells with that of normal cervical epithelium in each section, we found loss of HPV-16 E2 higher in CIN3 (15/24) than in CIN1 or CIN2 (3/7), and there is a significant trend that loss of HPV-16 E2 expression correlated with a >50% loss of TGF-beta1 at the lesion site (P < 0.05).


CONCLUSIONS
Our result showed co-suppression of HPV and TGF-beta1 expression during progression of cervical squamous cell cancer. Using antibody against HPV-16 E2 may be an auxiliary tool for the investigation of cervical tumor progression.
Torng
Pao-Ling
PL
The Department of Obstetrics & Gynecology, National Taiwan University College of Medicine, Taipei, Taiwan. pltorng@ha.mc.ntu.edu.tw
Chan
Wing-Yee
WY
Lin
Chin-Tang
CT
Huang
Su-Cheng
SC
D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000821:virology; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis*; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1; D014412:Tumor Virus Infections / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000737:chemistry* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000737:chemistry* / Q000821:virology
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1