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T. Nakanishi
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P1.02 - Poster Session with Presenters Present (ID 454)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.02-068 - The Impact of TP53 Overexpression on EMT and the Prognosis in Lung Adenocarcinoma Harboring Driver Mutations (ID 4489)
14:30 - 14:30 | Author(s): T. Nakanishi
- Abstract
Background:
Epithelial-mesenchymal transition (EMT) and p53 mutations are known to be pivotal for driving metastasis and recurrence in lung cancer, but the nature of these factors is not completely understood. Some papers have previously described the relationship between EMT and TP53 in other carcinomas, however there have been few reports about the impact of TP53 on EMT and prognosis in lung adenocarcinoma harboring driver mutations such as EGFR or K-ras.
Methods:
The aim of the present study is to clarify the impact of TP53 overexpression in lung adenocarcinoma with driver mutations. A total of 282 lung adenocarcinoma specimens were collected from patients who had undergone surgery in our institute from January 2001 to December 2007. Both EMT markers (E-cadherin, vimentin) and TP53 were analyzed through immunostaining of tumor specimens. The association between EMT and TP53 as well as the patients’ clinical information was integrated and statistically analyzed. EGFR and K-ras mutation were determined by single stranded conformational polymorphism and direct sequencing. Correlations were compared using Pearson's chi-square test and overall survival were compared using the log-rank test.
Results:
Both mesenchymal type (E-cadherin negative, vimentin positive) and TP53 overexpression were significantly correlated with poor prognosis (P=0.0001, P=0.0019). A positive correlation was found between EMT activation level and TP53 overexpression (P=0.017). TP53 overexpression was significantly correlated with poor prognosis in the subgroup of lung adenocarcinoma with driver mutation (EGFR or K-ras) (P=0.011, P=0.026), whereas there was no significant correlation between TP53 overexpression and the prognosis in adenocarcinoma without driver mutations (P=0.359).
Conclusion:
TP53 overexpression is supposed to be the key factor that affects EMT and the prognosis, and also might be an additional therapeutic target for lung adenocarcinoma with driver mutations.
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P2.02 - Poster Session with Presenters Present (ID 462)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.02-036 - Double Plasty Operation; A Procedure with Pulmonary Arterioplasty and Bronchoplasty against Centrally Located Non-Small Cell Lung Cancer (ID 5683)
14:30 - 14:30 | Author(s): T. Nakanishi
- Abstract
Background:
Against non-small cell lung cancer (NSCLC) centrally located and involving both artery and bronchus, resection with pulmonary arterioplasty and bronchialplasty are effective to avoid pneumonectomy and keep activity of daily life of patients. To elucidate the complications, prognosis, association with induction therapy and surgical technique of this complex operation with double plasty, we report the series in our institute.
Methods:
45 patients underwent bronchoplastic lobectomy due to NSCLC in our institute from January 2002 to December 2012 and 18 patients of these were received double plasty surgery (40.0%). As preoperatively, 4 received chemoradiotherapy (22.2%), 2 received chemotherapy (11.1%) and 1 received radiationtherapy (5.6%).
Results:
17 patients (94.4%) were added pedicled flap attachment on the bronchial anastomosis for reinforcement and prevention of contacting artery and bronchus. 10 of 16 patients (62.5%) who needed total pulmonary artery clamp were heparinized during clamping. No intraoperative and 30-day postoperative mortality was observed. Complications occurred in 7 patients (38.9%) and 1 patient died in 3 months after the surgery due to empyema which was induced by lung fistula developed with the influence of preoperative radiation therapy. Other 6 patients were all recovered from the complications without any sequel. There were no complications about bronchial anastomosis and the site of arterio-plasty. During observation period, 5 patients developed lung cancer recurrence and they all died. The overall 5-year survival rate was 66.7% although advanced stage.
Conclusion:
For locally advanced NSCLC, double plasty surgery can be valuable alternative to resect NSCLC completely and preserve lung function. Complications and overall survival rate are acceptable.
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P2.04 - Poster Session with Presenters Present (ID 466)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.04-018 - Comprehensive Copy Number Alteration and Gene Expression Analysis of Surgically Resected Thymic Carcinoma (ID 4725)
14:30 - 14:30 | Author(s): T. Nakanishi
- Abstract
Background:
Thymic carcinoma is rare and comparatively poor prognostic. Due to its rarity, our knowledge of treatments and prognostic biomarkers available for these tumors is limited. Previous reports revealed low genetic mutation frequency of the tumors, and the inverse correlation between the frequency of genetic mutation and copy number alteration (CNA). Based on these reports, we hypothesized tumorigenesis of thymic carcinomas is mostly caused by copy number and transcriptional alterations. To substantiate the hypothesis, we extracted and analyzed CNA and gene expression data from surgical samples to elucidate driver genes, druggable targets and prognostic factors.
Methods:
Between January 2009 and March 2016, patients underwent surgery for thymic epithelial tumor in our institution were reviewed. RNA and DNA of the tumors were extracted from FFPE operative samples, gene expression data were obtained by GeneChip Human Transcriptome Array 2.0 (affymetrix), and CNA were detected by OncoScan (affymetrix). These results were analyzed using Transcriptome analysis console (affymetrix) and Nexus expression for OncoScan (BioDiscovery). Upregulated genes in copy number gained region and down regulated genes in copy number lost region were selected as a candidate of tumorigenesis of thymic carcinoma.
Results:
We had 10 thymic squamous cell carcinoma samples. As a comparison, we use three samples of type A thymoma. CNA data from thymic squamous cell carcinoma showed similar characteristics, chromosome 1q gain, 6p and q loss, and 16q loss, corresponding with previous reports. Gene expression analysis of thymic carcinoma in comparison with type A thymoma revealed down regulation of the genes, BRD2, HSP90AB1, FOXO3, and MARCKS in chromosome 6, and MTSS1L in chromosome 16q. Figure 1
Conclusion:
We reported the results of genome wide gene expression and CNA analysis. We extracted some candidate genes, but farther validations are needed.
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P3.01 - Poster Session with Presenters Present (ID 469)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.01-048 - Cigarette Smoking is Associated with Epithelio-Mesenchymal Transition in Human Adenocarcinoma (ID 5531)
14:30 - 14:30 | Author(s): T. Nakanishi
- Abstract
Background:
Cigarette smoking (CS) is well known to cause lung cancer. In addition to the mechanisms of tumorigenesis of lung cancer with CS, a lot of evidences are currently accumulating that CS induces epithelio-mesenchymal transition (EMT) in tumor cells. The correlation of CS with the malignant properties of lung cancer remained elusive in clinical settings. Here we examined the clinical significance of CS with regard to EMT and malignant progression in human lung adenocarcinoma.
Methods:
Clinical samples were obtained from the 239 cases of resected lung adenocarcinoma which were consecutively operated from January 2001 to December 2007 in our institution. Pathological stage distribution of the cases by TNM classification (WHO, 7th edition) was below: 1A: 118, 1B: 71, 2A: 22, 2B: 4, 3A: 23, 3B: 1. Smoking history was taken from all the patients, then their smoking status were classified into 3 groups according to the Brinkman Index (Non;0, n=109: Light;1~400, n=29: Heavy;401~, n=101). The samples were immunostained against E-cadherin and Vimentin using tissue microarrays of resected specimens to assess the activation level of EMT. Then, we classified into 3 groups: the group ‘N’, E-cadherin(E+) and Vimentin(V-), “null” EMT activation; the group ‘F’, E-/V+, ‘full’ EMT; the group ‘P’, E-/V- or E+/V+, ‘partial’ EMT. The numbers of the group F/ P/ N were 38/ 93/ 108, respectively. Furthermore, DNA samples were extracted from frozen surgical samples and the mutations for the hot-spot exons of EGFR, K-ras, and p53 were detected by SSCP or direct sequencing methods. The differences of survival duration, pathological invasive factors, DNA mutations and EMT activation level were statistically analysed among smoking groups.
Results:
Significant difference was found in 5-year survival rate among 3 smoking groups: Non, 89.1%; Light, 89.5%; Heavy, 61.7%. Smoking status was significantly associated with EMT activation, DNA mutation status, local invasive factors, and lymph-node metastasis. In the tumors harboring either wild-type K-ras or wild-type p53, heavy smoking was associated with EMT activation (p<0.0001, p=0.0002, respectively), whereas no correlation with regard to EGFR staus.
Conclusion:
Smoking amounts had a significant association with EMT activation level and malignant progression of human adenocarcinoma. Heavy smoking was related with EMT activation of the tumors either with wild-type K-ras or p53.
