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. To confirm the overall validity of microarray data, we used real-time polymerase chain reaction.


RESULTS
The molecular signature of nodal metastasis was a composite of two paradoxical, but not mutually exclusive, expression patterns: metastatic cells are: (1) different from their primary tumor cells based on a few genes and (2) genetically similar, overall, to their primary tumor cells. Consequently, we found a 27-gene subset sufficient to differentiate nodal metastatic cells from primary tumor cells.


CONCLUSIONS
Thus, we concluded that a more accurate model of metastatic potential is based on a global primary tumor expression pattern along with the appearance of distinct metastatic variants. The 27-gene signature differentiating primary tumors from their metastatic cells may define non-small-cell lung carcinoma nodal metastatic potential.
Hoang
Chuong D
CD
Division of Cardiovascular and Thoracic Surgery, Department of Surgery, USA.
Guillaume
Tenner J
TJ
Engel
Sean C
SC
Tawfic
Sherif H
SH
Kratzke
Robert A
RA
Maddaus
Michael A
MA
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007834:Lasers; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics*; D008297:Male; D042282:Microdissection; D008954:Models, Biological; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction