Low IL-1alpha expression in bladder cancer tissue and survival.

Objective: To investigate whether the previously reported association between IL-1alpha mRNA levels and survival in urinary bladder cancer remains in an extended patient material and to search a mechanism behind a possible antitumoral activity of IL-1alpha.

Patients And Methods: IL-1alpha mRNA levels were determined in 164 tumors with quantitative TaqMan PCR.

Results: A large variation was found in mRNA levels of IL-1alpha. We found, by immunohistochemistry, that IL-1alpha is expressed by tumor rather than stromal cells. In a univariate Cox proportional hazards model, low levels (median split) of IL-1alpha mRNA were associated with a relative hazard ratio (RHR) of 1.7 (95% CI: 1.0-2.9) for cancer-specific death (n=157); a restriction to muscle invasive tumors (n=63) resulted in an RHR of 1.8 (0.9-3.3). In bivariate analyses, adjustment for age, stage and grade respectively, decreased the RHR and the association between IL-1alpha expression and cancer-specific survival was not statistically significant. Which factors to regard as confounders remains unclear.

Conclusions: Low levels of IL-1alpha mRNA expression are associated with an increased risk for cancer-specific death in the investigated material. However, confounding is an issue and to determine whether or not the observed association is causal, we need a defined mechanism and data from other studies.