Virtual Library
Start Your Search
M. Tsuboi
Author of
-
+
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
-
+
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): M. Tsuboi
- 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.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
-
+
P1.04-049 - The MRE11/RAD50/NBS1 Complex Was Impaired in Lung Cancer from Chromate-Exposed Workers (ID 2536)
09:30 - 09:30 | Author(s): M. Tsuboi
- Abstract
Background:
Our previous studies demonstrated that one third of lung cancers of chromate-exposed workers (chromate LC) showed high-degree microsatellite instability (MSI), most of which repressed DNA mismatch repair (MMR) hMLH1protein. MMR-deficient tumors are characterized by widespread changes in the number of microsatellites accumulating in both coding and non-coding sequences of many human genes. The MRE11–RAD50–NBS1 complex is essential for DNA double-strand break (DSB) repair performing by homologous recombination (HR) or non-homologous end joining (NHEJ). In gastric and colorectal cancers with MSI, the mono- or biallelic deletions in the poly(T)11 within MRE11 intron 4 and the frameshift mutations in the (A)9 repeat in RAD50 exon 13 were detected and the significant reduction of both proteins were identified.
Methods:
We used formalin-fixed paraffin-embedded materials from 36 chromate LC (28 cases; all male, mean age 56.8, squamous cell ca (SQ) 35, stage I 27, BI=488, mean chromate exposure 24 years) and 28 non-chromate LC (all male, mean age 61, SQ 28, stage I 8, BI=674). DNA was extracted and amplified using nested-PCR. The fragment analysis was performed using a capillary electrophoresis and GeneScan Analysis software (Applied Biosystem, USA).
Results:
In the poly(T)11 within MRE11 intron 4, 8 (29%) of 28 non-chromate LC showed 1bp deletion or insertion and 14 (52%) of 33 chromate LC showed 1bp deletion or insertion. In the (A)9 repeat in RAD50 exon 13, none of 27 non-chromate LC showed deletion or insertion and 4 (16%) of 25 chromate LC showed deletion. 67% of chromate LC with more than 3 MSI had abnormality of MRE11 gene, and 60% of chromate LC with 2 MSI had it. While, 27% of chromate LC with less than one MSI and 28% of non-chromate LC had it. 17% of chromate LC with more than 3 MSI had abnormality of MRE11 gene, and 10% of chromate LC with 2 MSI had it. While, 25% of chromate LC with less than one MSI had it and none of non-chromate LC had it.
Conclusion:
Half of chromate LC had the abnormality of the poly(T)11 within MRE11, which was associated with the degree of MSI. Sixteen percentage of chromate LC had the abnormality of the (A)9 repeat in RAD50. The carcinogenesis of chromate LC may be involved in the abnormality of DNA repair MRE11–RAD50–NBS1 complex.
-
+
P1.06 - Poster Session/ Screening and Early Detection (ID 218)
- Event: WCLC 2015
- Type: Poster
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
-
+
P1.06-005 - The Correlation between Visceral Pleural Invasion in T1a Non-Small Lung Cancer and Lymph Node Metastasis (ID 2638)
09:30 - 09:30 | Author(s): M. Tsuboi
- Abstract
Background:
Visceral pleural invasion (VPI) of non-small cell lung cancer (NSCLC) has been recognized as a poor prognostic factor. Peripheral lung cancers often invade visceral pleura, and positive VPI upstages the T category of tumors from T1a to T2a. In addition, it is possible that peripheral lung cancers with positive VPI causes lymph nodes metastasis because of subpleural lymphovascular invasion. In this study, we statistically analyzed the correlation between VPI and lymph node metastasis.
Methods:
129 patients with NSCLC and a tumor diameter of ≤ 2cm underwent lobectomy or segmentectomy with systematic lymph node dissection in Tokushima University Hospital between January 2008 to December 2013. Excluding 11 patients who were not examined by FDG-PET before the surgery, we reviewed the medical records of 118 patients to obtain information on age, sex, CEA, SUVmax, CT findings, pathological VPI and lymph node metastasis.
Results:
Patient characteristics were as follows: median age of 66.5 (range: 41-86); male/female: 52/66; histologic type adenocarcinoma/squamous cell carcinoma/other: 103/12/3. 13(36.1%) of 36 patients who were suspected to be with visceral pleural invasion by preoperative CT findings were diagnosed with pathological visceral pleural invasion. The mean SUVmax on FDG-PET in patients with VPI was significantly higher than that of patients without VPI(p=0.01). Pathological visceral pleural invasion was identified in 19(16.1%) of 118 patients and associated with high incidence of lymph node metastasis significantly on multivariable analyses (p=0.00).
Conclusion:
VPI is important factors of lymph node involvement in small peripheral lung cancers. It is difficult to identify VPI of peripheral lung cancers by preoperative CT findings. FDG-PET may be useful for diagnose VPI.
-
+
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)
-
+
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): M. Tsuboi
- 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.
