RESUMO
BACKGROUND: We have shown that colon and breast cancer contains large amounts of urokinase (uPA), and that these cells are the actual sites of its synthesis. We isolated a large complex molecule consisting of the beta-chain of uPA, both chains of haptoglobin (Hp), and part or all of an NCAM-like molecule. The question arose whether it would be possible to show the presence of Hp in the same cells where uPA was found. MATERIALS AND METHODS: Human colon and breast adenocarcinomas were investigated for expression of Hp and uPA by immunohistochemistry. Fluorescence in situ hybridization was used to identify the cells of origin of these antigens. RESULTS: Hp was expressed in 8 of 11 colon adenocarcinomas, and in 10 of 12 breast tumors. uPA was demonstrable on the cell membrane and in the cytoplasm of all 11 colon adenocarcinomas studied, and cytoplasmic uPA-mRNA was found in all cases. While uPA was also detected in some stromal and inflammatory cells, Hp was present abundantly in such cells, as well as in capillary endothelial cells. Hp-mRNA was also found in both colon and breast tumors wherever the antigens were expressed. CONCLUSIONS: uPA and Hp are produced by the cancer cells and are not taken up by stromal elements. While the role of uPA in the malignant process is well documented, that of Hp is largely unexplored. Its ubiquity, shown here, suggests that it is also involved in some aspects of that process.
Assuntos
Neoplasias da Mama/genética , Neoplasias do Colo/genética , Haptoglobinas/genética , Ativador de Plasminogênio Tipo Uroquinase/genética , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Neoplasias do Colo/enzimologia , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Feminino , Humanos , Hibridização In Situ , Hibridização in Situ Fluorescente , Estadiamento de Neoplasias , RNA Mensageiro/genética , RNA Neoplásico/genética , Neoplasias do Colo Sigmoide/enzimologia , Neoplasias do Colo Sigmoide/genética , Neoplasias do Colo Sigmoide/patologia , Neoplasias do Colo Sigmoide/cirurgiaRESUMO
BACKGROUND: The lack of prognostic factors in ductal carcinoma in situ (DCIS) that reliably identifies biologically aggressive tumors adversely affects optimal management. The urokinase-type plasminogen activator (uPA) system, comprised of its receptor, uPAR, and its inhibitor (PAI-1), are critical elements for tumor invasion and their expression in invasive breast cancer can predict clinical outcome. Expression of the uPA system in DCIS may be relevant in defining histological subsets of DCIS with invasive potential. METHODS: Localization of uPA, uPAR, and PAI-1 was investigated immunohistochemically in 60 DCIS tumors. FISH experiments were performed to determine whether uPA was present in cancer cells themselves or derived from stromal elements. RESULTS: uPA was ubiquitously expressed in the malignant ductal epithelium of 95% (57/60) of DCIS tumors studied. uPA-mRNA was detected in the malignant ductal epithelium but not the adjacent normal ductal epithelium and stromal elements. uPAR was expressed in 27% (6/22) of high-grade and 24% (9/38) of non-high-grade DCIS. In comparing coexpression, uPA and uPAR were coexpressed in only 25% (15/60) of tumors. PAI-1 was infrequently expressed in high grade (3/22) and absent in non-high-grade DCIS. CONCLUSIONS: This study identifies the presence of uPA, uPAR, and PAI-1 in both high-grade and non-high-grade DCIS. It may be speculated that coexpression of uPA and its receptor may identify subsets of DCIS with an increased risk for progression to invasive disease. If so, then expression of uPA system components may have prognostic and therapeutic significance in DCIS.