Lung cancer lymph node micrometastasis detection using real-time polymerase chain reaction: Correlation with vascular endothelial growth factor expression

Chukwumere E. Nwogu, Sai Yendamuri, Wei Tan, Eric Kannisto, Paul Bogner, Carl Morrison, Richard Cheney, Elisabeth Dexter, Anthony Picone, Mark Hennon, Alan Hutson, Mary Reid, Alex Adjei, Todd L. Demmy

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Objectives: 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.

Original languageEnglish (US)
Pages (from-to)702-708
Number of pages7
JournalJournal of Thoracic and Cardiovascular Surgery
Volume145
Issue number3
DOIs
StatePublished - Mar 1 2013
Externally publishedYes

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Neoplasm Micrometastasis
Vascular Endothelial Growth Factor A
Real-Time Polymerase Chain Reaction
Lung Neoplasms
Lymph Nodes
Vascular Endothelial Growth Factor D
Vascular Endothelial Growth Factor Receptor-3
Vascular Endothelial Growth Factor C
Vascular Endothelial Growth Factors
Non-Small Cell Lung Carcinoma
Keratin-7
Lymphangiogenesis
Nasal Mucosa
Palate
Carcinoembryonic Antigen
Cell Adhesion Molecules
Nonparametric Statistics
Mediastinoscopy
Lymphatic Metastasis
Carcinoma

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Lung cancer lymph node micrometastasis detection using real-time polymerase chain reaction : Correlation with vascular endothelial growth factor expression. / Nwogu, Chukwumere E.; Yendamuri, Sai; Tan, Wei; Kannisto, Eric; Bogner, Paul; Morrison, Carl; Cheney, Richard; Dexter, Elisabeth; Picone, Anthony; Hennon, Mark; Hutson, Alan; Reid, Mary; Adjei, Alex; Demmy, Todd L.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 145, No. 3, 01.03.2013, p. 702-708.

Research output: Contribution to journalArticle

Nwogu, CE, Yendamuri, S, Tan, W, Kannisto, E, Bogner, P, Morrison, C, Cheney, R, Dexter, E, Picone, A, Hennon, M, Hutson, A, Reid, M, Adjei, A & Demmy, TL 2013, 'Lung cancer lymph node micrometastasis detection using real-time polymerase chain reaction: Correlation with vascular endothelial growth factor expression', Journal of Thoracic and Cardiovascular Surgery, vol. 145, no. 3, pp. 702-708. https://doi.org/10.1016/j.jtcvs.2012.12.023
Nwogu, Chukwumere E. ; Yendamuri, Sai ; Tan, Wei ; Kannisto, Eric ; Bogner, Paul ; Morrison, Carl ; Cheney, Richard ; Dexter, Elisabeth ; Picone, Anthony ; Hennon, Mark ; Hutson, Alan ; Reid, Mary ; Adjei, Alex ; Demmy, Todd L. / Lung cancer lymph node micrometastasis detection using real-time polymerase chain reaction : Correlation with vascular endothelial growth factor expression. In: Journal of Thoracic and Cardiovascular Surgery. 2013 ; Vol. 145, No. 3. pp. 702-708.
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abstract = "Objectives: 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.",
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T2 - Correlation with vascular endothelial growth factor expression

AU - Nwogu, Chukwumere E.

AU - Yendamuri, Sai

AU - Tan, Wei

AU - Kannisto, Eric

AU - Bogner, Paul

AU - Morrison, Carl

AU - Cheney, Richard

AU - Dexter, Elisabeth

AU - Picone, Anthony

AU - Hennon, Mark

AU - Hutson, Alan

AU - Reid, Mary

AU - Adjei, Alex

AU - Demmy, Todd L.

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N2 - Objectives: 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.

AB - Objectives: 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.

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