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 stromal cell growth. Loss of responsiveness to TGF-beta 1 or loss of TGF-beta 1 itself may be important in the progression of cervical intraepithelial neoplasia (CIN) to invasive cervical carcinoma. METHODS. To examine the expression of TGF-beta in early stages of malignant transformation of the uterine cervix, paraffin embedded tissue samples from 11 patients with normal cervical epithelium, 15 with CIN I-III, 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-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 positive staining for the extracellular form of TGF-beta 1 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-beta 1 in neoplastic epithelium and increased expression of extracellular TGF-beta 1 in stroma associated with invasive cervical carcinoma suggest that an early event in the neoplastic transformation of cervical epithelia] cells may 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.
Comerci
J T
JT
Department of Obstetrics and Gynecology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York 10461, USA.
Runowicz
C D
CD
Flanders
K C
KC
De Victoria
C
C
Fields
A L
AL
Kadish
A S
AS
Goldberg
G L
GL
D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016212:Transforming Growth Factor beta / Q000032:analysis*; D002578:Uterine Cervical Dysplasia / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000737:chemistry*
D014408:Biomarkers, Tumor; D016212:Transforming Growth Factor beta