Decreased expression of human papillomavirus E2 protein and transforming growth factor‐β1 in human cervical neoplasia as an early marker in carcinogenesis
Journal
Journal of Surgical Oncology
Journal Volume
84
Journal Issue
1
Pages
17-23
Date Issued
2003
Author(s)
Abstract
Background and Objectives: 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)-β1. The purpose of this study is to investigate the possible cause-effect association between HPV and TGF-β1 during cervical tumorigenesis. Methods: We assessed the expression of HPV capsid proteins, HPV-16 E7, HPV-16 E2 (C and N terminals), TGF-β1, and their receptors TGF-β1 RI and RII by immunohistochemistry in 48 paraffin-embedded blocks of tumor tissue derived from patients of cervical neoplasia. Results: Expression of TGF-β1 decreased as tumor cells progressed from cervical intraepithelial neoplasia (CIN)1, CIN2, CIN3, to microinvasive carcinoma (P < 0.05). Levels of TGF-βRI and TGFβ-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-β1 (P < 0.05). By comparing the expression pattern of TGF-β1 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-β1 at the lesion site (P < 0.05). Conclusions: Our result showed co-suppression of HPV and TGF-β1 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. ? 2003 Wiley-Liss, Inc.
SDGs
Other Subjects
transforming growth factor beta receptor; transforming growth factor beta1; unclassified drug; virus e2 protein; virus protein; article; cancer tissue; carcinogenesis; clinical article; disease marker; female; human; human tissue; immunohistochemistry; immunoreactivity; priority journal; protein expression; squamous cell carcinoma; tumor cell; uterine cervix cancer; uterine cervix carcinoma in situ; uterine cervix epithelium; Wart virus; Carcinoma, Squamous Cell; Cervical Intraepithelial Neoplasia; DNA-Binding Proteins; Female; Humans; Oncogene Proteins, Viral; Papillomaviridae; Papillomavirus Infections; Receptors, Transforming Growth Factor beta; Transforming Growth Factor beta; Transforming Growth Factor beta1; Tumor Markers, Biological; Tumor Virus Infections; Uterine Cervical Neoplasms