Histological and immunohistochemical markers for progression prediction in transurethrally resected high-grade non-muscle invasive bladder cancer

Abstract

High-grade non-muscle-invasive bladder cancer (Non-MIBC) has a high risk of stage progression to muscle-invasive bladder cancer (MIBC) and could be managed either conservatively by transurethral resection of bladder tumor (TURBT) or more aggressively by radical cystectomy. The selection of patients who may benefit from early radical intervention is a challenge. To define useful prognostic markers for progression, we analyzed clinicopathological features and immunohistochemical expression patterns of E2F1, p27, survivin, p53, EZH2, IMP3, TSC1/hamartin, fatty acid synthase, androgen receptor, 14-3-3σ, MAGEA4, and NY-ESO-1 on 118 cases of high-grade Non-MIBC. During the mean follow-up period of 64.3 months, progression occurred in 18 patients (15.3%). Histologically, large amount of invasive component (> 50%) was noted in 35 cases (29.7%) and was strongly associated with progression. Among the 12 biomarkers, high expressions of E2F1 and nuclear p27 were noted in 46 cases (40.0%) and 14 cases (12.7%), respectively, and were associated with frequent progression. Using multivariate analysis, the proportion of invasive component and high E2F1 expression were independent prognostic factors for the prediction of progression. Our results indicated that large amount of invasive carcinoma component and high expressions of p27 and E2F1 were predictive markers for progression in Non-MIBC. Therefore, we suggest that these parameters, especially proportion of invasive carcinoma component and E2F1 expression, should be evaluated during pathologic examination and considered during selection of the appropriate management strategy for high grade Non-MIBC patients.

Keywords: Bladder cancer; high-grade; non-muscle-invasive bladder cancer; progression; urothelial carcinoma.

Figure 1

Representative immunohistochemical staining results in urothelial carcinoma: E2F1 (A), EZH2 (B), androgen receptor (C), p53 (D), IMP3 (E), FASN (F), tuberous sclerosis gene 1 (TSC1)/Hamartin (G), MAGEA4 (H), NY-ESO-1 (I), 14-3-3σ (J), nuclear survivin (K), cytoplasmic survivin (L), nuclear p27 (M) and cytoplasmic p27 (N).

Figure 2

Kaplan-Meier analysis for predicting progression. The invasive tumor component (A), E2F1 expression (B), and nuclear p27 expression (C) are associated with frequent progression.