Loss of maspin is a helpful prognosticator in colorectal cancer: a tissue microarray analysis

Mammary serpin (Maspin) belongs to the serine protease inhibitor (serpin) superfamily and has been identified as a tumor suppressor. In addition, a p53-dependent regulatory pathway of maspin in human cancer has been indicated. The role of maspin in the tumorigenesis and progression of colorectal cancer is still unclear. Therefore, the first aim of the present study was to determine the prognostic value of maspin protein expression for the recurrence-free and overall survival of patients with colorectal carcinoma undergoing left- or right-sided colectomy. Secondly, maspin expression was correlated with p53 protein expression to gain additional information about a possible regulatory influence of the wild-type p53 protein on maspin; it was also correlated with further patient and tumor characteristics (age, sex, TNM, disease stage, tumor localization, and grading). An immunohistochemical study was performed on 280 carcinoma specimens using the tissue microarray technique. In addition, 80 colorectal adenomas and 60 tumor-free tissues were investigated. Maspin protein expression was detectable in 88-100% of the adenomas and non-tumorous tissues and in 193 out of 280 carcinoma patients (69%; maspin-positive). After a median follow-up. of 102 months (23-140 months), the median recurrence-free survival was 80 months for maspin-positive cases (M+) and 42 months for maspin-negative cases (M-) (p = 0.02). The median long-term survival was 98 months for M+ and 57 months for M- (p = 0.03). After 5 years, M+ and M- patients had a total survival of 69% and 38%, and, after 10 years, 45% and 9%, respectively. Mutant type p53 expression was detectable in 178 colorectal carcinomas (64%). Mt p53 was positive in 91 out of 193 M+ (47%) compared with 87 of 87 M- (100%, p < 0.001). This study showed that loss of maspin protein correlates with p53 protein activity, with a higher likelihood for the development of tumor relapse, and with a decreased recurrence-free and overall survival in colorectal carcinomas. The determination of the immunohistochemical expression status of maspin might be a helpful independent prognosticator and an applicable tool for the development of therapeutic strategies for patients with this disease. (c) 2004 Elsevier GmbH. All rights reserved.