title: Lung cancer lymph node micrometastasis detection using real-time polymerase chain reaction: correlation with vascular endothelial growth factor expression.
abstract: OBJECTIVE
  Lymph node staging provides critical information in patients with non-small cell lung cancer (NSCLC). Lymphangiogenesis may be an important contributor to the pathophysiology of lymphatic metastases. We hypothesized that the presence of lymph node micrometastases positively correlates with vascular endothelial growth factors (VEGFs) A, C, and D as well as VEGF-receptor-3 (lymphangiogenic factors) expression in lymph nodes.
  
  
  METHODS
  Forty patients with NSCLC underwent preoperative positron emission tomography-computed tomography and mediastinoscopy. Real-time polymerase chain reaction (RT-PCR) assays for messenger RNA expression of epithelial markers (ie, cytokeratin 7; carcinoembryonic antigen-related cell adhesion molecule 5; and palate, lung, and nasal epithelium carcinoma-associated protein) were performed in selected fluorodeoxyglucose-avid lymph nodes. VEGF-A, VEGF-C, VEGF-D, and VEGF receptor-3 expression levels were measured in primary tumors and lymph nodes. Wilcoxon rank sum test was run for the association between the RT-PCR epithelial marker levels and VEGF expression levels in the lymph nodes.
  
  
  RESULTS
  RT-PCR for cytokeratin 7; carcinoembryonic antigen-related cell adhesion molecule 5; or palate, lung, and nasal epithelium carcinoma-associated protein indicated lymph node micrometastatic disease in 19 of 35 patients (54%). There was a high correlation between detection of micrometastases and VEGF-A, VEGF-C, VEGF-D, or VEGF receptor-3 expression levels in lymph nodes. Median follow-up was 12.6 months.
  
  
  CONCLUSIONS
  RT-PCR analysis of fluorodeoxyglucose-avid lymph nodes results in up-staging a patient's cancer. Micrometastases correlate with the expression of VEGF in lymph nodes in patients with NSCLC. This may reflect the role of lymphangiogenesis in promoting metastases.
authors: Department of Thoracic Surgery, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. chumy.nwogu@roswellpark.org
authors: Chukwumere E
authors: CE
authors: Nwogu
authors: Sai
authors: S
authors: Yendamuri
authors: Wei
authors: W
authors: Tan
authors: Eric
authors: E
authors: Kannisto
authors: Paul
authors: P
authors: Bogner
authors: Carl
authors: C
authors: Morrison
authors: Richard
authors: R
authors: Cheney
authors: Elisabeth
authors: E
authors: Dexter
authors: Anthony
authors: A
authors: Picone
authors: Mark
authors: M
authors: Hennon
authors: Alan
authors: A
authors: Hutson
authors: Mary
authors: M
authors: Reid
authors: Alex
authors: A
authors: Adjei
authors: Todd L
authors: TL
authors: Demmy
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D053552:Keratin-7 / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology*; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D061206:Neoplasm Micrometastasis / Q000473:pathology*; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D060888:Real-Time Polymerase Chain Reaction; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D018709:Statistics, Nonparametric; D014057:Tomography, X-Ray Computed; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D053552:Keratin-7; D019275:Radiopharmaceuticals; D042461:Vascular Endothelial Growth Factor A; D019788:Fluorodeoxyglucose F18; D040262:Receptors, Vascular Endothelial Growth Factor