Expression of Maspin Protein in Ductal Hyperplasia, Intraductal Carcinoma and Invasive Ductal Carcinoma of the Breast

Chu, Young Chae; Park, In Seo; Kim, Yoon Ju; Kim, Joon Mee; Han, Hye Seung; Han, Jee Young; Kim, Young Bae

Abstract

Maspin is a recently described gene with tumor suppressor activity. The gene product is a 42 kD protein with homology to the serpin family of protease inhibitors and may play a role as an inhibitor of tumor cell invasion. The prior observation that invasive breast cancers and their metastases showed decreased maspin protein expression by immunostaining supports this speculation. However, the role of maspin in breast cancer progression has not been studied in detail. We, therefore, studied maspin protein expression in a series of hyperplasia, atypical ductal hyperplasia, intraductal carcinoma and invasive carcinomas. Immunohistochemical staining (IHC) for maspin was performed on paraffin sections of 136 breast specimens using a commercially available monoclonal antibody. Among the 106 cases studied were 36 moderate/florid ductal hyperplasia, 11 atypical ductal hyperplasia (ADH), 29 intraductal carcinoma (IDC) (4 low grade, 13 intermediate grade, 12 high grade) and 30 invasive ductal carcinomas. Thirty cases of normal breast were also studied as control group. IHC stains were scored using a semiquantitative scoring system. The mean IHC scores for maspin for normal, moderate/florid hyperplasia, atypical ductal hyperplasia, intraductal carcinoma, and invasive carcinoma were 5.51 1.30, 7.36 0.72, 3.82 1.60, 4.48 2.69, 3.97 3.30, respectively. These scores for each category were statistically significant (p<0.05), except between ADH and IDC. Maspin protein expression was increased in most cases of moderate/florid hyperplasia, while maspin expression was more heterogeneous in ADH and IDC. In high grade IDC, maspin protein expression was stronger than low and intermediate grade IDC, and this suggests the possibility of a compensatory cellular response against the forces driving further tumor progression. Two thirds of invasive ductal carcinomas expressed maspin protein weakly and focally. All metastatic carcinomas of lymph nodes were negative for maspin. It is possible that high grade IDC with strong maspin expression may represent a subset less likely to progress to invasive cancer. This speculation merits investigation in clinical outcome studies.