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INTRODUCTION: We hypothesized an important role for stroma in non-small cell lung cancer (NSCLC) and investigated 34 samples with a special stroma focus using laser microdissection and Affymetrix U-133A arrays. The importance of stroma as a compartment which is variable in composition and often low in cell mass has often been underestimated. In an average bulk sample stroma makes only up for 10-30% of the material and in many studies stroma is even removed intentionally by microdissection. This traditional focus on the tumor epithelium may contribute to the difficulties in identifying survival markers.

METHODS: In this study we measured the transcriptome of 34 NSCLC bulk samples (12 adeno, 12 squamous cell, 5 large cell and 5 large cell neuroendocrine carcinomas) using Affymetrix U-133A gene chips. In addition, 4 squamous cell carcinomas were separated quantitatively by laser microdissection into the epithelial and the stromal fractions which were analyzed separately. On the basis of their expression ratios between the two compartments we assigned typical tumor and stroma genes.

RESULTS: This tumor-stroma gene spectrum was used to identify the predominant expression compartment of: a) typical cell marker genes e.g. keratins and collagens to test the approach, b) metabolic modules and pathways and c) 175 survival-relevant genes (survival >60 months vs. survival =2fold increase in the good prognosis group) are predominantly expressed in the stroma, and only 4 good markers are characteristic for the tumor fraction.

CONCLUSION: NSCLC diagnostics can significantly profit from a comprehensive transcriptome analysis of the stroma compartment of a cancer sample. Microdissection is a useful tool to extract from the stroma prognostically relevant information that often remains undetected in typical tumor bulk samples due to the low stroma content.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA