EXPRESSION OF TRANSFORMING GROWTH FACTOR-BETA-1 AND FACTOR-BETA-2 IN HUMAN PAPILLOMAVIRUS (HPV)-ASSOCIATED LESIONS OF THE UTERINE CERVIX

Human papillomaviruses (IBV) are implicated in the multistep process o f cervical carcinogenesis. Transforming growth factor beta(TGF-beta) i nhibits the proliferation of epithelial cells, and it has also been fo und to inhibit HPV gene expression in nontumorigenic epithelial cell l ines. In the present study, we examined the expression of TGF-beta 1 a nd TGF-beta 2 protein immunohistochemically (IHC) in a series of 95 HP V-positive and HPV-negative lesions of the uterine cervix, with specia l emphasis on HPV type, grade of cervical intraepithelial neoplasia (C IN), 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 epithe lial layers higher than that of TGF-beta 1, which showed also some nuc lear 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 wa s present slightly more frequently in HPV-CIN lesions (23/41, 56%) tha n in HPV-NCIN (HPV without CIN) specimens (13/27, 48%). TGF-beta 2 exp ression was detected in 39/41 (95%) of HPV-CIN and in 24/27 (89%) of H PV-NCIN specimens. TGF-beta 2 expression was not related to the clinic al course of the disease. TGF-beta 1 expression was most frequent in r egressed and persistent lesions (>60%), compared to 45% in progressed and 33% in the recurred lesions. The results suggest that TGF-beta (es pecially TGF-beta 2) expression is common in CIN lesions, but the patt ern and intensity of TGF-beta expression examined by IHC are not clear ly related to the grade of the lesions or their clinical course. Asses sment of the biological activity of TGF-beta s and their influence on HPV genes may shed more light on HPV-associated carcinogenesis. (C) 19 94 Academic Press, Inc.