Differential expression of uninary plasminogen activator, its receptor and inhibitor in ductal carcinoma in situ assessed by immunohistochemistry and in situ hybridization

T. Hurd, S. Sait, H. Lankes, R. Penetrante, S. Harvey

Research output: Contribution to journalArticle

Abstract

The urinary plasminogen activator (u-PA) system comprised of u-PA, its receptor (u-PAR) and inhibitor (PAI-1) has been implicated in the progression of invasive breast cancer. Its role in non-invasive breast cancer is not well understood. We hypothesize that expression of u-PA is an early event in the progression of breast tumors. To test this hypothesis, we examined the expression of u-PA, u-PAR and PAI-1 in ductal carcinoma in situ (DCIS). Paraffin-embedded sections of 36 DC1S tumors (18 comedo and 18 non-comedo) were stained with monoclonal antibodies against u-PA (3689), u-PAR (3932) and PAI-1 (3785) using a biotin - avidin - HRP system in a Ventana automated staining system. Fluorescein in situ hybridization (FISH) to detect u-PA-mRNA was performed on five tumors. u-PA was expressed in 34/36 (94%) tumors, whereas u-PAR was only expressed in 14 (39%). PAJ-1 on the other hand was expressed in 3/36 (8%) of in situ carcinomas all of which were comedo. u-PA and u-PAR were co-expressed in the tumor ductal epithelium of 13/36 in situ tumors (five comedo, eight non-comedo). Of 36 DCIS tumors, 28 lacked peritumoral stromal staining for u-PA, 3 3 for u-PAR and 28 for PAI-1. Only eight tumors demonstrated peritumoral strornal staining for u-PA. Surprisingly, peritumoral staining for u-PA was strong in low-grade and weak in highgrade tumors. Peritumoral stromal staining for PAI-1 was lost in 28/36 tumors, although the tumors strongly expressed u-PA and to a lesser extent u-PAR. Stroma surrounding the normal ducts stained strongly for PAI-1 (n= 28/36). Of the five tumors evaluated by FISH, u-PA-mRNA was found in the tumor epithelial cytoplasm but not in the surrounding stroma. Neither normal ducial epithelium nor its surrounding stroma expressed u-PA-mRNA. We conclude that: (1) Expression of u-PA appears to be an early event in DCIS progression followed by a later expression of u-PAR, (2) PAI-1 expression is down-regulated in the peritumoral stroma but not in the stroma surrounding the normal ducts, during this early event, (3) in situ hybridization studies with u-PA c-DNA suggest that tumor progression of DCIS occurs by an autocrine mechanism.

Original languageEnglish (US)
Number of pages1
JournalFibrinolysis and Proteolysis
Volume14
Issue numberSUPPL. 1
StatePublished - Dec 1 2000

ASJC Scopus subject areas

  • Hematology

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