Expression of interleukin-1 receptor-associated kinase-1 in non-small cell lung carcinoma and preneoplastic lesions.
OBJECTIVE
To identify the pattern of interleukin-1 receptor-associated kinase (IRAK-1) protein expression in non-small cell lung carcinoma (NSCLC) and corresponding preneoplastic lesions.


METHODS
Archived tissue from NSCLC (adenocarcinoma and squamous cell carcinoma; n = 306) and adjacent bronchial epithelial specimens (n = 315) were analyzed for the immunohistochemical expression of IRAK-1, and the findings were correlated with patients' clinicopathologic features. Furthermore, we investigated the correlation between IRAK-1 expression and expression of NF-kappaB and IL-1alpha in tumor specimens.


RESULTS
NSCLC tumors showed significantly higher cytoplasmic and lower nuclear IRAK-1 expression than normal epithelium. Squamous dysplasias had significantly higher cytoplasmic IRAK-1 expression than normal epithelium. In tumors, a significant positive correlation was detected between IRAK-1 expression (nuclear and cytoplasmic; P = 0.011) and IL-1alpha cytoplasmic expression (P < 0.0001). The correlation between the expression of the markers and patients' clinicopathologic features varied according to tumor histologic type and sex. High IRAK-1 cytoplasmic expression correlated with worse recurrence-free survival in women with NSCLC [hazard ratio (HR), 2.204; P = 0.033], but not in men. In adenocarcinoma, combined low level of expression of nuclear IRAK-1 and NF-kappaB correlated significantly with worse overall (HR, 2.485; P = 0.007) and recurrence-free (HR, 3.058; P = 0.006) survivals in stage I/II patients.


CONCLUSIONS
IRAK-1 is frequently expressed in NSCLC tissue specimens, and this expression is an early phenomenon in the sequential development of lung cancer. IRAK-1 is a novel inflammation-related marker and a potential target for lung cancer chemopreventive strategies.
Behrens
Carmen
C
Departmentsof Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4009, USA.
Feng
Lei
L
Kadara
Humam
H
Kim
Hyun-Jung
HJ
Lee
J Jack
JJ
Mehran
Reza
R
Hong
Waun Ki
WK
Lotan
Reuben
R
Wistuba
Ignacio I
II
D000230:Adenocarcinoma; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology*; D002294:Carcinoma, Squamous Cell; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000378:metabolism; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism*; D008175:Lung Neoplasms / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D011230:Precancerous Conditions / Q000201:enzymology*; D020545:Respiratory Mucosa / Q000378:metabolism
D014408:Biomarkers, Tumor; D007375:Interleukin-1; D016328:NF-kappa B; D053592:Interleukin-1 Receptor-Associated Kinases