Decline in the expression of the serine proteinase inhibitor maspin is associated with tumour progression in ductal carcinomas of the breast

Abstract

Maspin is an inhibitor of serine proteinases with tumour suppressor activity. Its expression appears to be reduced in advanced stages of breast cancer. A large series of archival breast tissue specimens has been examined, including normal glands (n=7), fibrocystic change (n=22), ductal carcinoma in situ (DCIS, n=12), infiltrating carcinomas (n=128) and their lymph node metastases (n=65), using a specific monoclonal antibody. Myoepithelium invariably showed strong maspin expression. In epithelial cells, the strongest expression was found in normal breast and fibrocystic change. A significant stepwise decrease in maspin expression (p<0.0001) occurred in the sequence DCIS - invasive cancer - lymph node metastasis. However, a subset of infiltrating carcinomas showed strong maspin expression, significantly associated with a lower rate of lymph node metastasis at the time of diagnosis (p<0.01). This was independent of tumour size and grade. The in vivo observations presented here are in keeping with data obtained in prior in vitro experiments. Maspin emerges as an indicator of tumour progression and metastatic potential, and might be exploited to predict breast cancer prognosis. According to in vitro data, its tumour suppressor activity is likely to involve both the modulation of cell motility/invasiveness and the inhibition of angiogenesis.

Clinical significance of Maspin promoter methylation and loss of its protein expression in invasive ductal breast carcinoma: correlation with VEGF-A and MTA1 expression

“…Some earlier studies on Maspin demonstrate its tumor-suppressive properties [47][48][49]. Overall, our study supports previous clinical studies which have shown that Maspin plays an important tumor-suppressor role in breast tumorigenesis.…”

Prognostic significance of the maspin tumor suppressor gene in pulmonary adenocarcinoma

“…3 Survival of patients with respect to maspin expression and P-stage by the Cox-Mantel statistic. The difference between groups became more evident in P-stage II patients in whom the 5-year survival rates of the maspin-positive and maspin-negative groups were 69% and 17%, respectively (P = 0.048), whereas those in P-stage I patients were 73% for maspin-positive and 68% for maspin-negative (P = 0.75) and those in P-stage III patients were 25% for maspin-positive and 18% for maspin-negative (P = 0.73) A stepwise reduction in maspin levels in conjunction with tumor progression as seen in breast cancer (Maass et al 2001c) was not observed in the present study. However, bronchial basal cells in the surrounding tissues usually expressed maspin, and this was occasionally accompanied by maspin expression in surface bronchial epithelial cells.…”

“…The maspin gene has been mapped to human chromosome 18q21.3-q23 and was originally isolated from normal mammary epithelium by subtractive hybridization (Zou et al 1994;Seftor et al 1998). Recently, it was reported that downregulation of maspin expression correlates with progression and poor prognosis in breast, prostate (Luppi et al 1996;Maass et al 2001b;Maass et al 2001c;Machtens et al 2001), oral and tongue cancers (Xia et al 2000;Yasumatsu et al 2001). To the best of our knowledge, however, there have been no investigations concerning maspin expression and its relation to prognosis in pulmonary adenocarcinoma.…”

DNA methylation or histone modification status in metastasis and angiogenesis-related genes: a new hypothesis on usage of DNMT inhibitors and S-adenosylmethionine for genome stability

“…It was shown that stepwise reduction of maspin expression occurring along with the progression from ductal mammary carcinoma to invasive carcinoma to lymph node metastasis and also the lack of maspin expression in breast cancer seems to be associated with the short diseasefree survival [98,99]. By contrast, an increase in maspin levels can block the invasion, metastasis, motility, and progression of these cancer types [96,100,101].…”