Maspin protein expression correlates with tumor progression in non-muscle invasive bladder cancer

Abstract

Maspin is a 42-kDa protein that belongs to the family of serine protease inhibitors. It is involved in various physiological processes. In cancer tissue, Maspin was found to influence angiogenesis, tumor growth, metastasis and the prognosis of tumor patients. This study was performed to analyze the involvement of Maspin in transitional cell carcinoma of the bladder as well as its prognostic impact in a large patient cohort. Specimens from 162 non-muscle invasive bladder cancer patients (pTa, 91; pT1, 71) treated by transurethral resection with a minimum 3-year follow-up (median 58.5 months) were included in the present investigation. Tissue microarrays were constructed, and the specimens were immunohistochemically stained for Maspin protein expression. Each tissue specimen was assessed on a staining scale ranging from 0 (no staining) to 300 (strong staining) and correlated with various clinicopathological parameters. Maspin protein expression predicted progression with a sensitivity of 95% and a specificity of 70% (p<0.001). In predicting recurrence, Maspin staining showed 52% sensitivity and 67% specificity (p<0.05). Kaplan-Meier analyses were performed, and a low Maspin protein expression was correlated with a higher incidence of tumor progression (p<0.0001). However, expression levels of Maspin protein did not distinguish between pTa and pT1 specimens. Multivariate analyses indicated Maspin expression as an independent factor for predicting progression (p<0.0001) and recurrence (p<0.05). The present results suggest that the Maspin protein expression is an independent prognostic indicator for predicting recurrence and progression to muscle invasive disease. This study further emphasizes a possible clinical role of this novel tumor suppressor gene in transitional cell carcinoma of the bladder.

Figure 1

Maspin protein expression in pTa/pT1 TCC cases in correlation with (A) tumor recurrence (p<0.05) and (B) tumor progression (p<0.0001). The y-axis shows Maspin staining levels.

Figure 2

A decreased Maspin protein expression in pTa/pT1 TCC cases was significantly associated with an increased likelihood of tumor progression and a shorter progression-free survival (group B, Maspin level <175) in the Kaplan-Meier analysis (p<0.0001, Log-rank test). The y-axis shows the probability of non-progression.

Figure 3

Maspin staining in TCC. (A) A strong Maspin protein expression with cytoplasmic and nuclear staining in non-recurrent and non-progressive pTa tumor. (B) Faint Maspin protein expression without nuclear staining in a progressive pTa tumor.