Analysis of paired primary lung and lymph node tumor cells: a model of metastatic potential by multiple genetic programs.

Background: The current paradigm of metastasis proposes that rare cells within primary tumors acquire metastatic capability via sequential mutations, suggesting that metastases are genetically dissimilar from their primary tumors. We tested this hypothesis by examining the molecular differences, if any, between primary tumor cells and matched lymph node metastatic cells in human non-small-cell lung carcinoma specimens.

Methods: We performed transcriptional profiling studies on malignant cells from 11 pairs of stage III tumors and their tumor-positive lymph nodes using multiple, complementary analytic techniques.

Expression profiling of non-small cell lung carcinoma identifies metastatic genotypes based on lymph node tumor burden.

Objective: This study hypothesized that non-small cell lung carcinoma cells from primary tumors isolated by laser capture microdissection would exhibit gene expression profiles associated with graded lymph node metastatic cell burden.

Methods: Non-small cell lung carcinoma tumors (n = 15) were classified on the basis of nodal metastatic cell burden by 2 methods, obtaining 3 groups: no metastasis, micrometastasis, and overt metastasis. We then performed microarray analysis on microdissected primary tumor cells and identified gene expression profiles associated with graded nodal tumor burden using a correlation-based selection algorithm coupled with cross-validation analysis.