Gene expression levels of epidermal growth factor receptor, survivin, and vascular endothelial growth factor as molecular markers of lymph node involvement in patients with locally advanced rectal cancer.
BACKGROUND
Patients diagnosed with locally advanced rectal cancer usually receive surgical resection and adjuvant chemoradiation therapy. Lymph node involvement is an important clinical prognostic factor affecting recurrence and survival. Few studies have explored molecular markers associated with lymph node involvement of rectal cancer.


METHODS
Tissue was obtained from 59 patients with locally advanced rectal cancer who were treated with adjuvant chemoradiation therapy. We assessed messenger RNA (mRNA) levels of genes involved in pathways of angiogenesis (vascular endothelial growth factor [VEGF], cyclooxygenase-2), apoptosis (survivin), tumor growth and epidermal growth factor receptor (EGFR), DNA repair (ERCC1, Rad51), and the DNA synthesis in tumor tissue and tumor-adjacent normal tissue from paraffin-embedded samples using laser-capture microdissection methods.


RESULTS
Twenty-four patients had no involvement of regional lymph nodes and 35 had lymph node metastases. In univariate analysis, patients with lymph node involvement had higher mRNA levels of VEGF and survivin in tumor tissue and EGFR in tumor-adjacent normal tissue compared with patients with no lymph node involvement (P < 0.1; t test). Multivariate analysis using recursive partitioning showed that mRNA levels of EGFR, survivin, and Rad51 are primarily responsible for delineating node positive from node negative.


CONCLUSIONS
Gene expression of VEGF, survivin, and EGFR could be associated with lymph node involvement in patients with locally advanced rectal cancer. Further independent studies of those gene expression levels and lymph node involvement are warranted to better characterize the associations.
Yang
Dongyun
D
Department of Preventive Medicine, Humboldt-University, Berlin, Germany.
Schneider
Sylke
S
Azuma
Mizutomo
M
Iqbal
Syma
S
El-Khoueiry
Anthony
A
Groshen
Susan
S
Agafitei
Dana
D
Danenberg
Kathleen D
KD
Danenberg
Peter V
PV
Ladner
Robert D
RD
Lenz
Heinz-Josef
HJ
D000328:Adult; D000368:Aged; D015415:Biomarkers; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008207:Lymphatic Metastasis; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D012004:Rectal Neoplasms / Q000235:genetics / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
C107489:BIRC5 protein, human; D015415:Biomarkers; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000077022:Survivin; D042461:Vascular Endothelial Growth Factor A; D066246:ErbB Receptors