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S. Sakiyama
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MINI 32 - Topics in Localized Lung Cancer (ID 166)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:D. Boffa, T. D'Amico
- Coordinates: 9/09/2015, 18:30 - 20:00, 201+203
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MINI32.01 - Computed Tomography Lymphography by Transbronchial Injection of Iopamidol for Preoperative Non-Small Cell Lung Cancer Patients (ID 3009)
18:30 - 18:35 | Author(s): S. Sakiyama
- Abstract
- Presentation
Background:
Sentinel node (SN) is defined as the first node draining a tumor, and should be the first site affected in lymphatic dissemination. Recently, with the increased incidence of small sized non-small cell lung cancer (NSCLC), segmentectomy is again under evaluation for clinical T1a N0 NSCLC patients. In the ongoing trial regarding segmentectomy (JCOG0802), the eligibility criteria for segmentectomy include a prerequisite of no lymph node metastasis by intraoperative findings because node-positive cases have a chance to be locoregionaly controlled and to be correctly staged by converting to lobectomy. Therefore, intraoperative sampling and frozen sectioning of true SNs is important in ensuring the radicality of segmentectomy. The objective of this study was to assess the safety and the feasibility of computed tomography (CT) lymphography by transbronchial injection of a water-soluble extracellular CT contrast agent which was developed as a new method for identifying SNs in patient with NSCLC.
Methods:
Between April, 2010 and January, 2015, clinical stage I NSCLC patients who were candidates for lobectomy or segmentectomy were enrolled in this study. An ultrathin bronchoscope was inserted to the target bronchus under the guidance of virtual bronchoscopic navigation images. CT images of the chest were obtained 30 seconds after 2 or 3ml of iopamidol was injected through a microcatheter. SNs were identified when the maximum CT attenuation value of the lymph nodes in postcontrast CT images increased by 30 Hounsfield units or more compared to precontrast images. Patients underwent video-assisted thoracic surgery lobectomy with standard lymph node dissection. SNs were harvested according to findings of CTLG and to intraoperative findings of near-infrared fluorescence imaging with indocyanine green. All lymph nodes, including SNs, were histopathologically examined by standard hematoxylin and eosin staining.
Results:
The ultrathin bronchoscope could access targeted bronchus, and iopamidol was delivered into the peritumoral area in all 41 patients without any complications. SNs were identified in 38 of 41 patients (92.7%), and the average number of SNs was 1.4 (range: 1-4). Lymph node metastases were found in 6 cases, including one false-negative case. Enlargement of lymphatic vessel was seen in 3 out of 6 (50%) cases with lymph node metastases, whereas it was seen in 6 out of 35 cases (17%) without lymph node metastases.
Conclusion:
CT lymphography by transbronchial injection of iopamidol was a safe and feasible method to identify SNs in clinical stage I NSCLC patients. Lymphatic remodeling including peritumoral lymphangiogenesis and enlargement of lymphatic vessel has been reported to one of the crucial step of lymph node metastasis of cancer. Enlargement of lymphatic vessel seen in CT lymphography may be a risk factor for lymph node metastasis of NSCLC.
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P2.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 225)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.08-033 - DNA Methylation on Promotor Region of RASSF1 Gene in Thymic Neuroendocrine Tumor Is Higher than B3 Thymoma and Thymic Squamous Cell Carcinoma (ID 2544)
09:30 - 09:30 | Author(s): S. Sakiyama
- Abstract
Background:
RASSF1 gene, located in 3p21.3, has eight exons and two promotor regions. RASSF1 is very famous tumor suppressor gene in various cancers. It was reported that DNA methylation on promotor region of RASSF1 in lung cancer, bladder cancer, and breast cancer and so on was higher, additionally low expression of RASSF1 was possible to cause to be poor prognosis. It is few reports about epigenome status in thymic epitherial tumors. We planned to explore DNA methylation in thymic epitherial tumors cyclopedically.
Methods:
①DNA and RNA were extracted from frozen specimen of B3 thymomas (8cases), thymic cancers (8cases), and thymic neuroendocrine tumors(NET)(3cases). ②DNA was treated by bisulfite conversion. ③DNA methylation level in 470000 CpG sites were measured by infinium methylation assay (Human methylation 450K; ILLMINA) exhaustively. ④DNA methylation on promotor regions of RASSF1 was measured by pyrosequencing（PyroMARK[TM]system;QIAGEN）. ⑤Expression level of mRNA was measured by Real time RT-PCR(Thermal Cycler Dice® Real Time System Single; Takara), using TaqMan Gene Expression Assays (Hs00200394_m1；Applied Biosystems). Internal reference gene is GAPDH（Hs02758991_g1；Applied Biosystems). ⑥Expression level of protein was analysed by immunostaining. Anti-RASSF1a antibody（Anti-RASSF1a antibody [3F3] ab23950, Mouse monoclonal, abcam）was used by CSAⅡmethod（DAKO CSA II, Biotin-Free Catalyzed Amplification System）.
Results:
Significant difference of DNA methylation was recognized by analysis of infinium methylation assay. All 11 CpG sites were configured on 1α promotor region of RASSF1 in this assay. This assay showed DNA methylation level was highest in NET group. DNA methylation level were 70.9±4.9% in NET, 22.2±20.0% in thymic cancer, 14.3±12.3% in B3 thymoma. ( NET vs Cancer/B3 t-test：P<0.00001). Pyrosequencing showed DNA methylation level were 24.0±13.1% in NET, 3.0±0.5% in thymic cancer, 3.0±0.9% in B3 thymoma. Real time RT-PCR showed that relative expression level (/normal thymus) were 0.48±0.31 in NET, 1.02±0.82 in carcinoma, 2.13±2.93 in B3 thymoma ( NET vs Carcinoma/B3 t-test：P=0.16). Immunostaining of RASSF1 was scored by stain intensity and stain extend. Immunostaining scoring of RASSF1 showed expression inhibition rate were 66% in NET, 50% in thymic cancer, 14% in B3 thymoma.
Conclusion:
The infinium methylation assay showed that DNA methylation on promotor region of RASSF1 in NET is higher than B3 thymoma and thymic cancer. The pyrosequencing validated this result. It was tendency to suppress the mRNA or protein expression of RASSF1 in NET, compared to other tumors. It is possible that aberrant DNA methylation on promotor region of RASSF1 may be specific change in NET among thymic epitherial tumors. Now we collected 8 formalin-fixed paraffin-embedded samples of thymic NETs to perform pyrosequencing and immunostaining of RASSF1 gene.
