ALTERED EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA-1 IN CERVICAL NEOPLASIA AS AN EARLY BIOMARKER IN CARCINOGENESIS OF THE UTERINE CERVIX

BACKGROUND. Transforming growth factor-beta 1 (TGF-beta 1) is a potent growth inhibitor of epithelial cell growth, but can also stimulate st romal cell growth. Loss of responsiveness to TGF-beta 1 or loss of TGF -beta 1 itself may be important in the progression of cervical intraep ithelial neoplasia (CIN) to invasive cervical carcinoma. METHODS. To e xamine the expression of TGF-beta in early stages of malignant transfo rmation of the uterine cervix, paraffin embedded tissue samples from 1 1 patients with normal cervical epithelium, 15 with CIN I-III, 12 with microinvasive, and 18 with invasive squamous cell carcinoma were exam ined using an immunohistochemical technique. Tissues were immunostaine d with polyclonal antibodies that react with intracellular and extrace llular forms of TGF-beta 1. RESULTS. Percent positive staining for the intracellular form of TGF-beta 1 was 100% for normal epithelium, 73.3 % for CIN, and 44.1% for invasive carcinomas (P = 0.002). Percent posi tive staining for the extracellular form of TGF-beta 1 was 63.6% for s troma underlying normal epithelium, 60% for stroma associated with GIN , and 94.1% for stroma surrounding invasive cancer (P = 0.007). CONCLU SIONS. Decreased expression of intracellular TGF-beta 1 in neoplastic epithelium and increased expression of extracellular TGF-beta 1 in str oma associated with invasive cervical carcinoma suggest that an early event in the neoplastic transformation of cervical epithelial cells ma y involve the loss of TGF-beta 1. Tumor progression may be indirectly promoted by TGF-beta 1 secreted into or produced by supporting stromal elements. (C) 1996 American Cancer Society.