Intense inflammation in bladder carcinoma is associated with angiogenesis and indicates good prognosis

Abstract

The aim of this study was to investigate the prognostic influence of microvessel density using the hot spot method in 107 patients diagnosed with transitional cell carcinoma of the bladder. In each case, inflammation was found in the invasive carcinoma, therefore we classified the degree of inflammation as minimal, moderate or intense. Microvessel density was then reevaluated in each tumour in areas corresponding to these three categories. Median microvessel density irrespective of degree of inflammation was 71. Areas of minimal, moderate and intense inflammation were found in 48, 92 and 32 tumours. Microvessel density increased significantly with increasing degree of inflammation. Disease-specific survival was improved if areas of intense inflammation were present in the carcinoma (P=0.004). High microvessel density, irrespective of the degree of inflammation, was associated with a significantly better disease-specific survival (P=0.01). Multivariate analysis using death of disease as endpoint demonstrated an independent prognostic value of N-classification (N0, hazard ratio (HR)=1 vs N1, HR=2.89 (range, 1.52-5.52) vs N2, HR=3.61 (range, 1.84-7.08)), and intense inflammation, HR=0.48 (range, 0.24-0.96). Malignancy grade, T classification and microvessel density were not independent significant markers of poor outcome. In conclusion, inflammation was significantly correlated to microvessel density, and areas of intense inflammation were an independent marker of good prognosis.

Figure 1

Disease-specific survival stratified by MVD_max evaluated irrespective of degree of inflammation dichotomised on the median value (MVD_max high ⩾71).

Figure 2

Intraobserver data for the reproducibility of the MVD counts. Left column shows the bivariate scatter plots. In each plot the correlation coefficient r², slope with corresponding 95% confidence interval, and intercept with the Y-axis with corresponding 95% confidence interval are listed. Right column shows the difference plots; solid line : mean intraobserver difference and dotted line : 95% limits of agreement (±2 s.d.).

Figure 3

(A–C) Shows examples of minimal, moderate and intense inflammation, respectively. CD34-positive vessels are highlighted with red and counterstained with haematoxylin. Notice in C carcinoma cells lying in close relation to the inflammatory cells. (D) Shows VEGF staining of an adjacent section to B. Notice the intense staining of inflammatory cells in the stroma and of the carcinoma cells. Bar is 100 μm.

Figure 4

Disease-specific survival stratified by tumours with areas of intense and moderate inflammation in bladder carcinoma.

Figure 5

Distribution of MVD evaluated in areas of different degrees of inflammation. Inflammation group 1 was ‘minimal inflammation’, group 2 was ‘moderate inflammation’, and group 3 was ‘intense inflammation’.