Decreased synthesis and expression of TGF-β1, β2, and β3 in epithelium of HPV 16-positive cervical precancer: a study by microdissection, quantitative RT-PCR, and immunocytochemistry
✍ Scribed by Amira M. El-Sherif; Rashmi Seth; Patrick J. Tighe; David Jenkins
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 316 KB
- Volume
- 192
- Category
- Article
- ISSN
- 0022-3417
No coin nor oath required. For personal study only.
✦ Synopsis
Cervical carcinogenesis is a multistep process initiated by `high-risk' human papillomaviruses (HR-HPVs), most commonly HPV 16. Transforming growth factor-beta (TGF-b) inhibits epithelial proliferation and down-regulates transcription of E6/E7 genes of HPV. Altered TGF-b expression may be important in carcinogenesis. Quantitative RT-PCR was used to investigate TGF-b1, b2, and b3 mRNA levels in nine specimens of normal cervix and 15 cervical precancers (eight HPV-positive, including ®ve HPV 16-positive). Immunocytochemical expression of TGF-b1, b2, and b3 was examined in cervical intraepithelial neoplasia (CIN) positive for HPV 16 (26), and in HPV-negative, normal ectocervical epithelium (9); reserve cell hyperplasia (12); and immature (7) and mature (15) squamous metaplasia. The intensity of staining for TGF-b1 was measured using grey-scale image analysis. Microdissection was used to investigate epithelial and stromal (excluding crypts) levels of TGF-b1 mRNA in HPV 16-positive cervical precancer. Normal cervix, including reserve cells and immature and mature metaplasia, showed strong immunocytochemical expression of all TGF-b isoforms. Expression was decreased in the basal third of the epithelium in CIN 1, in the basal and middle thirds in CIN 2, and in all layers in CIN 3. Quantitative analysis of TGF-b1 expression showed that the changes in CIN compared with normal ectocervix and mature metaplasia were statistically highly signi®cant ( p<0.001, ANOVA). TGF-b1, b2, and b3 mRNA levels showed a signi®cant decrease only in the ®ve HPV 16-positive CIN samples when compared with normal ( p=0.0034, 0.0033, and 0.029, respectively). TGF-b mRNA levels in HPV 16-positive epithelium also decreased from normal through low-grade to high-grade precancer. Stromal TGF-b1 was absent or very low compared with epithelial production and was not altered in HPV 16 precancer. Progressive loss of epithelial TGF-b expression and synthesis may be important in HPV 16-associated human cervical carcinogenesis.