Expression of transforming growth factor-beta 1 and -beta 2 in human papillomavirus (HPV)-associated lesions of the uterine cervix.

Human papillomaviruses (HPV) are implicated in the multistep process of cervical carcinogenesis. Transforming growth factor beta(TGF-beta) inhibits the proliferation of epithelial cells, and it has also been found to inhibit HPV gene expression in nontumorigenic epithelial cell lines. In the present study, we examined the expression of TGF-beta 1 and TGF-beta 2 protein immunohistochemically (IHC) in a series of 95 HPV-positive and HPV-negative lesions of the uterine cervix, with special emphasis on HPV type, grade of cervical intraepithelial neoplasia (CIN), and the clinical course of the disease. Expression of TGF-beta 1 was found in 56/95 (59%) and that of TGF-beta 2 in 87/95 (92%) of the specimens. Cytoplasmic TGF-beta 2 staining was localized in the epithelial layers higher than that of TGF-beta 1, which showed also some nuclear staining and was located in the basal cells of the epithelium as well. TGF-beta 1 was expressed in 36/68 (53%) of HPV-positive samples and in 16/21 (76%) of HPV-negative samples; TGF-beta 2 expression was detectable in 63/68 (93%) and 18/21 (86%), respectively. TGF-beta 1 was present slightly more frequently in HPV-CIN lesions (23/41, 56%) than in HPV-NCIN (HPV without CIN) specimens (13/27, 48%). TGF-beta 2 expression was detected in 39/41 (95%) of HPV-CIN and in 24/27 (89%) of HPV-NCIN specimens. TGF-beta 2 expression was not related to the clinical course of the disease. TGF-beta 1 expression was most frequent in regressed and persistent lesions (> 60%), compared to 45% in progressed and 33% in the recurred lesions. The results suggest that TGF-beta (especially TGF-beta 2) expression is common in CIN lesions, but the pattern and intensity of TGF-beta expression examined by IHC are not clearly related to the grade of the lesions or their clinical course. Assessment of the biological activity of TGF-beta s and their influence on HPV genes may shed more light on HPV-associated carcinogenesis.