Expression of syndecan-1 and expression of epidermal growth factor receptor are associated with survival in patients with nonsmall cell lung carcinoma.
BACKGROUND
Recently, the authors identified molecular signatures and pathways associated with nonsmall cell lung carcinoma histology and lung development. They hypothesized that genetic classifiers of histology would provide insight into lung tumorigenesis and would be associated with clinical outcome when evaluated in a broader set of specimens.


METHODS
Associations between patient survival and immunostaining for 11 representative histologic classifiers (epidermal growth factor receptor [EGFR], CDK4, syndecan-1, singed-like, TTF-1, keratin 5, HDAC2, docking protein 1, integrin alpha3, P63, and cyclin D1) were examined using a tissue microarray constructed from nonsmall cell lung carcinoma specimens.


RESULTS
Sixty-three tumors were examined, including 43 adenocarcinomas, 11 large cell carcinomas, and 9 squamous cell carcinomas. Sixty-three percent of tumors were clinical Stage I lesions, and 37% were Stage II-III lesions. In a multivariate analysis that controlled for age, gender, and race, syndecan-1 expression was found to be associated with a significant reduction in the risk of death (hazard ratio, 0.31 [95% confidence interval, 0.18-0.87]; P < 0.05). Multivariate analysis also indicated that EGFR expression was associated with a significant reduced risk of death.


CONCLUSIONS
The authors demonstrated that expression of either of the nonsmall cell lung carcinoma subtype classifiers syndecan-1 and EGFR was associated with a 30% reduction in the risk of death, with this reduction being independent of histology and other confounders. The results of the current study suggest that loss of expression of these histologic classifiers is associated with biologic aggressiveness in lung tumors and with poor outcome for patients with such tumors. If their significance can be validated prospectively, these biomarkers may be used to guide therapeutic planning for patients with nonsmall cell lung carcinoma.
Shah
Lori
L
Department of Medicine, Columbia University College of Physicians & Surgeons, New York, New York 10032, USA.
Walter
Kristin L
KL
Borczuk
Alain C
AC
Kawut
Steven M
SM
Sonett
Joshua R
JR
Gorenstein
Lyall A
LA
Ginsburg
Mark E
ME
Steinglass
Kenneth M
KM
Powell
Charles A
CA
D000230:Adenocarcinoma / Q000401:mortality; D000368:Aged; D018287:Carcinoma, Large Cell / Q000401:mortality; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality*; D002294:Carcinoma, Squamous Cell / Q000401:mortality; D019938:Cyclin D1 / Q000032:analysis; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000032:analysis; D066246:ErbB Receptors / Q000032:analysis*; D005260:Female; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D039001:Integrin alpha Chains / Q000032:analysis; D053555:Keratin-5; D007633:Keratins / Q000032:analysis; D008175:Lung Neoplasms / Q000401:mortality*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D008565:Membrane Proteins / Q000032:analysis; D015999:Multivariate Analysis; D009687:Nuclear Proteins / Q000032:analysis; D011509:Proteoglycans / Q000032:analysis*; D011518:Proto-Oncogene Proteins / Q000032:analysis; D012097:Repressor Proteins / Q000032:analysis; D053668:Syndecan-1; D053667:Syndecans; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000032:analysis
C081876:CKAP4 protein, human; D039001:Integrin alpha Chains; C503940:KRT5 protein, human; D053555:Keratin-5; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D011509:Proteoglycans; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C508241:SDC1 protein, human; C035026:SRPRA protein, human; D053668:Syndecan-1; D053667:Syndecans; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; C406210:integrin alpha 10; D019938:Cyclin D1; D007633:Keratins; D066246:ErbB Receptors; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases