title: Expression of interleukin-1 receptor-associated kinase-1 in non-small cell lung carcinoma and preneoplastic lesions.
abstract: 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.
authors.affiliation: Departmentsof Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4009, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: Behrens
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.forename: Humam
authors.initials: H
authors.lastname: Kadara
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.forename: Reza
authors.initials: R
authors.lastname: Mehran
authors.forename: Waun Ki
authors.initials: WK
authors.lastname: Hong
authors.forename: Reuben
authors.initials: R
authors.lastname: Lotan
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
mesh_terms: 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
chemical_list: D014408:Biomarkers, Tumor; D007375:Interleukin-1; D016328:NF-kappa B; D053592:Interleukin-1 Receptor-Associated Kinases