Expression of maspin in non-muscle invasive bladder carcinoma: Correlation with tumor angiogenesis and prognosis

Objectives: Maspin is a member of the serpin (serine protease inhibitor) family and has been shown to be a suppressor of tumor growth and an inhibitor of angiogenesis as well as metastasis in several types of tumors. We studied expression patterns of Maspin in pTa/pT1 urothelial carcinoma of the bladder and compared them with microvessel density (MVD) for two vascular markers (CD34 and CD105) and correlated the findings with clinical outcome. Material and Methods: We investigated tumor samples of 110 patients undergoing transurethral resection for pTa/pT1 bladder carcinoma (pTa, n = 84; pT1, n = 26; grade 1, n = 22; grade 2, n = 81; grade 3, n = 7). Immunohistochemical studies were performed using the monoclonal antibodies, anti-human Maspin (NCL Maspin), anti-CD34 Class II and anti-CD105. Maspin expression level was classified according to the staining intensity (- to+++). The blood vessels (CD34) and specifically proliferating bloodvessels (CD105) were counted as vessels per field (microvessel density, MVD). Results: Of the 110 tumors, 27 showed a negative immunostaining for Maspin, 46 tumors stained +, 29 stained ++, and 8 stained +++. Maspin expression correlated inversely with CD34 reactivity. In tumors with loss of or only weak Maspin expression, the MVD for CD34 was 21.7 vessels per field, and 4.2 vessels per field for proliferating vessels (CD 105), whereas Maspin-positive tumors had an MVD of 17.7 vessels per field (CD34), and of 6.0 vessels per field (CD105). Complete follow-up data are available in 92 patients. After a median follow-up of 25 months, 18 of the 92 patients (19.6%) had tumor recurrences. Tumors with decreased Maspin expression (-/+) had a shorter disease-free interval (23 months) than patients with stronger Maspin (++/+++.) expression (29 months), whereas a Kaplan-Meier analysis and the log-rank test showed no significant difference in disease-free survival between the patients. Conclusion: The clinical importance of Maspin has been mainly investigated regarding tumor progression or metastasis. We found a decreased Maspin expression in a large portion of pTa/pT1 bladder tumors. Even if patients with decreased Maspin expression have a slightly shorter disease-free survival Maspin does not appear to be a promising prognostic marker. (C) 2003 Elsevier B.V. All rights reserved.