Tissue microarray analysis of the prognostic value of E-cadherin, Ki67, p53, p27, survivin and MSH2 expression in upper urinary tract transitional cell carcinoma.

OBJECTIVES: Invasive upper urinary tract transitional cell carcinoma (UUT-TCC) has a poor prognosis (survival <50% at 5 years), and tumor stage and grade often fail to predict outcome. Our purpose was to establish whether the expression of Ki67, p53, p27, E-cadherin, survivin or MSH2 can provide prognostic information in UUT-TCC.

METHODS: The following data from the files of 62 patients treated for UUT-TCC over 12 years were collated: age at diagnosis, prior history of cancer, tobacco consumption, tumor stage (including surgical margins) and grade, and disease progression. Immunohistochemistry (IHC) for Ki67, p53, p27, E-cadherin, survivin and MSH2 was performed on tissue microarray sections from tumor tissue.

RESULTS: Overall, 31 patients died with metastasis from UUT-TCC. Mean survival was 20+/-16 months (range 2-83). In a univariate analysis, advanced age (>68 years), high stage, and loss of E-cadherin and high Ki67 expression were associated with a poor prognosis and disease recurrence. In a multivariate analysis, the independent factors of prognosis and recurrence were E-cadherin (p=0.001; p=0.004), age (p=0.022; p=0.008), and high stage (p=0.023; p=0.008).

CONCLUSIONS: E-cadherin is a useful independent prognostic factor in UUT-TCC, for use in addition to age and tumor stage. It is of particular interest to predict recurrence in patients with low grade non-invasive tumors. Ki67 expression is informative but less significant. Survivin, p53, p27 and MSH2 have no prognostic value.