Urokinase gene expression indicates early invasive growth in squamous celllesions of the uterine cervix

The plasminogen activating system plays a key role in the cascade of tumour -associated proteolysis leading to extracellular matrix degradation and str omal invasion. Changes in the expression of this system, consisting of urok inase- and tissue-type plasminogen activators (uPA and tPA, respectively), plasminogen activator inhibitors (PAI-1, PAI-2) and uPA receptor, have been associated with tumour aggressiveness in a variety of solid malignant tumo urs, This paper describes a study of squamous intraepithelial lesions (SILs , n = 36), squamous cell carcinomas (SCCs, n = 42), and normal mucosa (n = 5) of the uterine cervix by in situ hybridization with S-35-labelled RNA pr obes, uPA transcripts were absent from normal mucosa and non-invasive lesio ns, but present in atypical epithelial cells of all microinvasive carcinoma s (n = 19) and in some of the more advanced invasive carcinomas (n = 11), P AI-1 transcripts were found in stromal cells of most tissue samples with, h owever, significantly increased levels in invasive SCC compared with SIL, m icroinvasive SCC, and normal mucosa, uPA-positive invasive carcinomas often displayed additional PAI-1 expression by tumour cells. At variance with uP A, tPA transcripts were found in atypical epithelial cells of low- and high -grade SILs, In the majority of SCCs tested (27/29 cases), the HPV 16 E6/E7 oncogene and uPA transcription were correlated. uPA and PAI-1 expression i ndicates invasive growth when expressed by atypical epithelial cells of squ amous cervical lesions. Moreover, the presence of uPA transcripts is indica tive of early invasive growth. uPA and tPA seem to have different functions in the development of invasive properties in uterine cervical squamous epi thelium. Copyright (C) 1999 John Wiley & Sons, Ltd.