The expression of TUCAN, an inhibitor of apoptosis protein, in patients with advanced non-small cell lung cancer treated with chemotherapy.
BACKGROUND
TUCAN is a caspase recruitment domain (CARD)-containing protein involved in tumor biology by regulating apoptosis and the NFkappaB pathway. Inhibition of caspase-9 may cause drug resistance. The pattern of expression, localization and prognostic value of TUCAN in the tumors of patients with non-small cell lung cancer (NSCLC) treated with chemotherapy were assessed in this study.


METHODS
Using immunohistochemistry, the expression and localization of TUCAN was evaluated in forty-nine tumor specimens from patients with NSCLC who underwent neoadjuvant chemotherapy (32 stage IIB or IIIA), or palliative chemotherapy (17 stage IIIB or IV). The correlation between TUCAN expression and subcellular localization, major patient characteristics, response to the treatment and overall survival were assessed.


RESULTS
TUCAN expression was detectable in 34 out of 49 (69%) tumor specimens. Among the positively-stained specimens, three patterns of localization were observed: 5 samples (11%) showed exclusive nuclear localization, 13 samples (27%) contained only cytoplasmic staining and 15 (31%) showed both cytoplasmic and nuclear localization. There was no significant correlation between the localization of TUCAN and response to chemotherapy. Although TUCAN expression was not correlated with outcome, interestingly, exclusive cytoplasmic localization of TUCAN predicted shorter survival (p = 0.027).


CONCLUSIONS
Our results suggest that differential localization of TUCAN may be a prognostic factor for NSCLC, despite the lack of predictive value for response to chemotherapy.
Checinska
Agnieszka
A
Departments of Medical Oncology , VU University Medical Center, 1081 HV Amsterdam, The Netherlands.
Oudejans
Joost J
JJ
Span
Simone W
SW
Rodriguez
Jose A
JA
Kruyt
Frank A E
FA
Giaccone
Giuseppe
G
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D053468:CARD Signaling Adaptor Proteins / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D013347:Subcellular Fractions / Q000378:metabolism
D000970:Antineoplastic Agents; D053468:CARD Signaling Adaptor Proteins; C455623:CARD8 protein, human; D009363:Neoplasm Proteins