Aberrant maspin expression is involved in early carcinogenesis of gallbladder cancer

Mammary serine protease inhibitor (maspin, SERPIN-B5) is expressed in normal human mammary epithelial cells and is known to be down-regulated during cancer progression. Aberrant maspin expression has been reported in a number of cancers, including pancreatic and ovarian cancer. Recently, we identified several genes that may be tumor markers for gallbladder (GB) cancer using a DNA microarray method. There are no published data regarding maspin expression in GB cancer. The aims of this study were to determine maspin expression in normal mucosa, adenoma, dysplasia and carcinoma of GB, and to compare the pattern of maspin expression in early and advanced GB cancers. One hundred one patients with primary GB cancer who underwent resection between March 1999 and May 2008 were included. Twenty-five adenomas and 10 normal GB specimens were also included. We performed tissue microarray construction and immunohistochemical staining to evaluate maspin expression. The immunostaining results were estimated semiquantitatively by one pathologist. The positive rate of maspin expression was 59.4% (60/101) in GB cancer, whereas no maspin was expressed in adenomas and normal mucosa of GB. In case of positive maspin expression, it was gradually increased from dysplasia to carcinoma. No significant difference in the positive rate of maspin expression between early and advanced cancer was detected (49% versus 60%; P = 0.731). This result suggests that maspin expression may be involved in dysplasia-carcinoma sequence and the early steps of GB carcinogenesis.