Endobronchial ultrasound doppler image features correlate with mRNA expression of HIF1-α and VEGF-C in patients with non-small-cell lung cancer.
BACKGROUND
We attempted to assess the correlation between the Doppler mode image patterns during endobronchial ultrasound-guided (EBUS) transbronchial needle aspiration and the expression of angiogenesis-related molecules within lymph nodes in patients with non-small-cell lung cancer.


METHODS
Thirty-eight archived EBUS- transbronchial needle aspiration samples of lymph nodes (27 metastatic and 11 nonmetastatic) in patients with non-small-cell lung cancer with Doppler mode ultrasound image were analyzed. The Doppler mode image of the vasculature of the targeted lymph node was categorized into the following groups: normal blood flow, low blood flow (LBF), and high blood flow (HBF). Vascular index ratio (vascular area/lymph node area) of each metastatic lymph node was calculated. Total RNA and protein was extracted and analyzed for expression of HIF-1α, VEGF-A, and VEGF-C by quantitative RT-PCR and enzyme-linked immunosorbent assay.


RESULTS
Within the 27 metastatic lymph nodes, eight were categorized into the LBF group and 19 into the HBF group. Vascular index ratio was significantly higher in HBF than LBF (p = 0.0003). mRNA expression of HIF-1α and VEGF-A was significantly higher in metastatic lymph nodes than in benign lymph nodes (p < 0.0001). Compared with LBF and HBF, HIF-1α mRNA expression was significantly higher in LBF (p = 0.01) and VEGF-C mRNA expression was significantly higher in HBF (p = 0.0315). There was no significant difference in protein expression by enzyme-linked immunosorbent assay analysis.


CONCLUSIONS
The vascularity of metastatic lymph nodes observed by EBUS correlates with the mRNA expression of HIF-1α and VEGF-C (not VEGF-A). This correlation is a clinical utility that needs to be evaluated further.
Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Canada. nakajii@fc.med.miyazaki-u.ac.jp
Takahiro
T
Nakajima
Takashi
T
Anayama
Terumoto
T
Koike
Masato
M
Shingyoji
Lianne
L
Castle
Hideki
H
Kimura
Ichiro
I
Yoshino
Kazuhiro
K
Yasufuku
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001999:Bronchoscopy; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019160:Endosonography; D004797:Enzyme-Linked Immunosorbent Assay; D005500:Follow-Up Studies; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D060787:Neoplasm Grading; D009389:Neovascularization, Pathologic; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics* / Q000378:metabolism
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C