Plasminogen activator inhibitor type 2 in breast cancer

Abstract

Summary The serine protease urokinase plasminogen activator (uPA) is causally involved in cancer invasion and metastasis. Activity of this protease in vivo is controlled principally by two inhibitors, one of which is plasminogen activator inhibitor type 2 (PAI-2). In this study, we show that PAI-2 levels were significantly higher in primary breast carcinomas (n = 152) than benign breast tumours (n = 18). In the primary cancers, PAI-2 levels correlated weakly but significantly with those of uPA and PAI-1, but not with tissue type plasminogen activator (tPA) or uPA receptor (uPAR) levels. Using Northern blotting, mRNA for PAI-2 was&found in 28.6% of 49 primary breast cancers. In contrast to findings at the protein level, PAI-2 mRNA levels failed to correlate with those for uPA or PAI-1. After immunocytochemistry with primary cancers, PAI-2 was detected predominantly in the malignant cells of primary carcinomas but was also present in stromal cells. Using the median value as a cut-off point, PAI-2 showed no significant relationship with either disease-free interval or overall survival. However, using an optimum cut-off value, patients with low levels of PAI-2 had a worse outcome than those with a high level. We conclude that, unlike PAI-1, high levels of PAI-2 may be a favourable prognostic marker in breast cancer.

Significance of plasminogen activator inhibitor 2 as a prognostic marker in primary lung cancer: association of decreased plasminogen activator inhibitor 2 with lymph node metastasis

“…Furthermore, in the u-PA-positive cases, the survival rate of patients with negative mRNA expression of PAI-2 was significantly worse than that of patients with positive mRNA expression of PAI-2 in lung cancers. These results support the findings that depressed PAI-2 antigen detected by the immunoenzymic method is correlated with a shortened disease-free survival in breast cancer (Foekens et al, 1995;Duggan et al, 1997) and that the occurrence of lymph node metastasis follows diminished expression of PAI-2 in breast cancer (Ishikawa et al, 1996), non-small-cell lung cancer (Nagayama et al, 1994) and colon cancer (Naitoh et al, 1995). Our previous and present findings and the reports of others suggest that PAI-2 is a more important inhibitor of u-PA activity than PAI-1.…”

High tumor tissue concentration of plasminogen activator inhibitor 2 (PAI‐2) is an independent marker for shorter progression‐free survival in patients with early stage endometrial cancer

“…In contrast, several studies in breast cancer have indicated that high tumor tissue concentrations of PAI-2 are associated with better prognosis. 15,20,21,37 Findings in patients with small cell lung cancer seem to agree with those in breast cancer, since low tumor content of PAI-2 correlated with advanced stage of the disease. 38 PAI-2 is abundant in placental tissue and is also known to be produced by activated human monocytes and certain malignant cells.…”

Maspin – the most commonly-expressed gene of the 18q21.3 serpin cluster in lung cancer – is strongly expressed in preneoplastic bronchial lesions

“…However, high pAI-2 levels are associated with aggressive disease in colorectal cancer (Verspaget et al, 1995) and in bladder cancer cell lines, pAI-2 expression correlates with tumour stage and with a low overall survival (Champelovier et al, 2002). Paradoxically, in breast cancer, high levels of pAI-2 have been reported to be a favourable prognostic marker (Duggan et al, 1997) and in vitro pAI-2 expression can inhibit cancer cell invasion and metastasis (Mueller et al, 1995). In this study, pAI-2 was over-represented in 14/35 NSCLCs compared to corresponding normal lung.…”