The prognostic value of basement membrane morphology, tumour histology and morphometry in superficial bladder cancer

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Abstract
This analysis evaluated the prognostic importance of clinical, histological (WHO grade, papillary status, tumour-infiltrating lymphocytes) and morphometric factors (mitotic index, mean nuclear area, SD of nuclear area) in a cohort of 132 patients with a Ta-Tl transitional cell bladder cancer followed-up for over 8 years. Special attention was given on the state of the subepithelial basement membrane (BM) and subepithelial vascular density as demonstrated by type IV collagen immunostaining. Defects in the BM and dense vascular network were related to nodular growth pattern, high histological grade, rapid cancer cell proliferation and a dense inflammatory cell infiltrate (tumour-infiltrating lymphocytes, TIL) in tumour stroma. The most important predictor of progression was the mitotic index (PP=0.0054), the state of the BM (P=0.0056), density of TIL (P=0.0193), WHO grade (P=0.0356) and papillary status (P=0.0448). In univariate survival analysis the mitotic index (PPP=0.0013) and WHO grade (P=0.01) predicted survival. In a multivariate analysis the mitotic index (PP=0.008) were independent predictors. The results show that the evaluation of the mitotic rate and investigation of the continuity of the BM should be done whenever the prognosis of Ta-Tl tumours of the bladder is assessed invasive (Torti and Lum 1984). At present we are not able to identify accurately those patients who are at an increased risk of an invasive disease. Flow cytometry (Blomjous et al. 1989; Masters et al. 1989) and morphometry (Blomjous et al. 1989; Lipponen et al. 1990, 1992a, b) provide more objective prognostic information than WHO grade in superficial TCC. Recent analyses suggest that the host defence mechanisms play an important role in the modulation of progression of TCC (Lipponen et al. 1992 a). The subepithelial basement membrane (BM) is a mechanical barrier through which the cancer cells must penetrate before TCC becomes invasive, and basement-membrane-degrading proteases play an important part in this process (Liotta 1984). At present, commercially available antibodies against collagen type IV and laminin identify structures related to BM with a high specificity and thus the state of the BM can be easily assessed (Christensen 1992). In TCC the importance of intact BM as a prognostic marker has been previously assessed only in few studies without long clinical follow-up (Conn et al. 1987; Daher et al. 1987; Schapers et al. 1990). The role of the BM has been rarely evaluated in superficial tumours although in these the state of the BM should have importance in preventing invasion. In this study the primary biopsy specimens from 132 superficial TCC were stained with type IV collagen antibody and the staining results were related to clinical, histological, morphometric and follow-up data.