Cg. Ferreira et al., Assessment of IAP (inhibitor of apoptosis) proteins as predictors of response to chemotherapy in advanced non-small-cell lung cancer patients, ANN ONCOL, 12(6), 2001, pp. 799-805
Background: Expression of inhibitor of apoptosis family proteins (IAPs) has
been shown in vitro to decrease chemosensitivity through caspase inhibitio
n. However, the role of IAPs as predictors of response to chemotherapy in c
ancer patients remains to be determined.
Patients and methods: Using immunohistochemistry, we assessed the expressio
n of the IAP proteins c-IAP1, c-IAP2, and XIAP on tumors from 55 patients w
ith advanced non-small-cell lung cancer (NSCLC) treated with chemotherapy,
and correlated that with the observed response to chemotherapy, time to pro
gression and overall survival.
Results: Differences were observed in the pattern of staining among the IAP
proteins. The expression of c-IAP2 and XIAP was exclusively cytoplasmic, w
hereas c-IAP1 also displayed nuclear staining. The median expression of tum
or cells for c-IAP1, c-IAP2, and XIAP was 70%, 45%, and 25%, respectively,
and a correlation was observed between c-IAP1 and c-IAP2 (P = 0.004), and c
-IAP1 and XIAP expression (P = 0.013). However, no association was seen bet
ween the expression of these proteins and sex, age, tumor size, stage, hist
ology and grade of differentiation. Interestingly, expression of c-IAP1, c-
IAP2, and XIAP did not predict response to chemotherapy. In addition, the e
xpression of IAPs had no impact on the time to progression or overall survi
val of this group of patients.
Conclusions: Our results indicate that: 1) there are differences in the lev
el of expression and in the subcellular distribution of c-IAP1, c-IAP2, and
XIAP in tumors derived from NSCLC patients. 2) The expression of c-IAP1, c
-IAP2 and XIAP does not predict the response to chemotherapy in patients wi
th advanced NSCLC. 3) The relation between expression of IAPs and chemosens
itivity in cancer patients may be more complex than anticipated by in vitro
data.