Assessment of IAP (inhibitor of apoptosis) proteins as predictors of response to chemotherapy in advanced non-small-cell lung cancer patients.
BACKGROUND
Expression of inhibitor of apoptosis family proteins (IAPs) has been shown in vitro to decrease chemosensitivity through caspase inhibition. However, the role of IAPs as predictors of response to chemotherapy in cancer patients remains to be determined.


METHODS
Using immunohistochemistry, we assessed the expression of the IAP proteins c-IAP1, c-IAP2, and XIAP on tumors from 55 patients with advanced non-small-cell lung cancer (NSCLC) treated with chemotherapy, and correlated that with the observed response to chemotherapy, time to progression 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. whereas c-IAP1 also displayed nuclear staining. The median expression of tumor 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 between the expression of these proteins and sex, age, tumor size, stage, histology and grade of differentiation. Interestingly, expression of c-IAP1, c-IAP2, and XIAP did not predict response to chemotherapy. In addition, the expression of IAPs had no impact on the time to progression or overall survival of this group of patients.


CONCLUSIONS
Our results indicate that: 1) there are differences in the level 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 with advanced NSCLC. 3) The relation between expression of IAPs and chemosensitivity in cancer patients may be more complex than anticipated by in vitro data.
Ferreira
C G
CG
Department of Medical Oncology, Academic Hospital Vrije Universitiet, Amsterdam, The Netherlands.
van der Valk
P
P
Span
S W
SW
Jonker
J M
JM
Postmus
P E
PE
Kruyt
F A
FA
Giaccone
G
G
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011506:Proteins / Q000378:metabolism; D013223:Statistics as Topic; D016019:Survival Analysis; D044767:Ubiquitin-Protein Ligases; D051636:X-Linked Inhibitor of Apoptosis Protein
D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins; D011506:Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C494833:BIRC2 protein, human; D044767:Ubiquitin-Protein Ligases