Can tissue microarray-based analysis of protein expression predict recurrence of stage Ta bladder cancer?

Being able to predict the recurrence or progression of non-muscle-invasive bladder cancer would facilitate effective planning of treatments and follow-up. Biomarkers are needed that can supply prognostic information beyond that provided by clinical and pathological parameters. Tissue microarray (TMA)-based analysis of Ta bladder tumours was used to investigate the prognostic value of expression of several proteins involved in bladder carcinogenesis.

Tumour tissue from 52 patients with Ta bladder cancer was investigated. At least three 0.6 mm punch cores from each tumour were placed in a paraffin array block. Tumour expression of tumour protein 53 (TP53), CDH1 (E-cadherin), proliferating cell nuclear antigen (PCNA), cyclooxygenase-2 (COX2), fibroblast growth factor receptor-3 (FGFR3) and epidermal growth factor receptor (EGFR) was quantified by immunohistochemistry (IHC) and correlated with time to recurrence. Median follow-up time was 3.1 years. Whole-section IHC analysis was performed to validate significant findings.

Of all patients, 69% (36/52) experienced recurrence. In univariate analysis, recurrence was associated with multifocality, number of earlier recurrences and a low quantity score for EGFR. In a multivariate model, a low EGFR quantity score was correlated with early recurrence (hazard ratio = 5.5, p = 0.003). However, whole-section IHC results for EGFR differed markedly from the TMA findings (κ = 0.07) and no association with time to recurrence was found (p = 0.65).

Expression of EGFR measured by TMA-IHC, but not by whole-section IHC, was associated with early recurrence. The results suggest that the proteins assessed have no predictive value for recurrences. Concerns are raised regarding the methodology and generalization of results obtained with TMA-IHC.