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.


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.
Seddighzadeh
M
M
Cancer Center Karolinska, R8:03, Karolinska Institute and Hospital, SE-171 76, Stockholm, Sweden. gunnar.ssteineck@onkpat.ki.se
Larsson
P
P
Ulfgren
A-C
AC
Onelöv
E
E
Berggren
P
P
Tribukait
B
B
Torstensson
A
A
Norming
U
U
Wijkström
H
H
Linder
S
S
Steineck
G
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001707:Biopsy, Needle; D002423:Cause of Death; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D013548:Sweden; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology
D007375:Interleukin-1; D012333:RNA, Messenger