Abstract
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, syndecanโ1, singedโlike, TTFโ1, keratin 5, HDAC2, docking protein 1, integrin ฮฑ3, P63, and cyclin D1) were examined using a tissue microarray constructed from nonsmall cell lung carcinoma specimens.
RESULTS
Sixtyโthree tumors were examined, including 43 adenocarcinomas, 11 large cell carcinomas, and 9 squamous cell carcinomas. Sixtyโthree percent of tumors were clinical Stage I lesions, and 37% were Stage IIโIII lesions. In a multivariate analysis that controlled for age, gender, and race, syndecanโ1 expression was found to be associated with a significant reduction in the risk of death (hazard ratio, 0.31 [95% confidence interval, 0.18โ0.87]; 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 syndecanโ1 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. Cancer 2004. ยฉ 2004 American Cancer Society.