Transforming growth factor-Pl (TGF-Pl) is a potent growth inhibitor of epithelial cell growth, but can also stimulate stromal cell growth. Loss of responsiveness to TGF-/)l or loss of TGF-P1 itself may be important in the progression of cervical intraepithelial neoplasia (CIN) to invasive cervical carcinoma.
METHODS.
To examine the expression of TGF-P in early stages of malignant transformation of the uterine cervix, paraftin embedded tissue samples from 11 patients with normal cervical epithelium, 15 with CIN 1-111, 12 with microinvasive. and 18 with invasive squamous cell carcinoma were examined using an immunohistochemical technique. Tissues were immunostained with polyclonal antibodies that react with intracellular and extracellular forms of TGF-P1.
RESULTS.
Percent positive staining for the intracellular form of TGF-P1 was 100% for normal epithelium, 73.3% for CIN, and 44.1% for invasive carcinomas (P = 0.002). Percent positive staining for the extracellular form of TGF-Pl was 63.6% for stroma underlying normal epithelium, 60% for stroma associated with CIN, and 94.1% for stroma surrounding invasive cancer ( P = 0.007).
CONCLUSIONS. Decreased expression of intracellular TGF-P1 in neoplastic epithelium
and increased expression of extracellular TGF-Pl in stroma associated with invasive cervical carcinoma suggest that an early event in the neoplastic transformation of cervical epithelial cells may involve the loss of TGF-P1. Tumor progression may be indirectly promoted by TGF-PI secreted into or produced by supporting stromal elements. CMCer 1996; 721107-14. 0 1996