Virtual Library
Start Your Search
Toshi Menju
Author of
-
+
P2.03 - Biology (ID 162)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
-
+
P2.03-09 - Arf6-Related Invasive Pathway Deteriorated Patients’ Prognosis in Mutant EGFR Lung Adenocarcinoma (ID 2937)
10:15 - 18:15 | Presenting Author(s): Toshi Menju
- Abstract
Background
Arf6-related pathway has been reported to be activated in the downstream of EGF stimulation and to play pivotal roles in invadopodia formation and integrin recyclying leading to cancer invasion and metastasis. EGFR is well known to be constitutively activated without EGF stimulation in lung cancer harboring the mutations in its kinase domain. Here, we have examined the clinicopathological significance of Arf6-related pathway especially in mutant EGFR (mEGFR) lung adenocarcinomas.
Method
Clinical samples were obtained from the 239 cases of resected lung adenocarcinoma which were consecutively operated from January 2001 to December 2007 in Kyoto University Hospital. Then, tissue microarrays (TMAs) were made from all the cases. Using DNA samples extracted from fresh frozen tumors, EGFR mutations were detected by SSCP or direct sequencing methods as previouly published.
Immunohistochemical stainings were performed on TMAs against the molecules of Arf6-related pathway: Grb2, GEP100, Arf6, AMAP1, EPB41L5. The positivity of all molecules was judged according to their H-scores: intensities multiplied by percentages. Clinicopathological data were integrated and reviewed. Statistical analyses for overall (OS) or disease-free survival (DFS) were performed by Kaplan-Meirer methods and log-rank tests. Categorical data were analysed by Pearson’s test. Cox hazard models were applied for multivariate analyses. P-values less than 0.05 were considered significant.
Result
Among all cases, mEGFR was found in 113 cases, whereas 118 cases had wild type EGFR (wtEGFR) mutations. Common mutations in EGFR were detected in 104 cases (92.0%). Positivity of each molecule in mEGFR cases was the following: Grb2/ GEP100/ Arf6/ AMAP1/ EPB41L5; 11.9/ 27.7/ 48.2/ 52.7/ 56.3%. Positivity in all molecules showed no significant difference between exon 19 and exon21 mutation cases.
Visceral pleural involvments were significantly increased in AMAP1- or EPB41L5-positive groups and lymph node metastases were significantly increased in Grb2- or EPB41L5-positive groups.
Univariate analyses showed that 5-year OS rates were significantly low in Grb2 or AMAP1 positive groups specific to mEGFR cases (Grb2-/+: 89.0 vs 69.2%; p=0.0051, AMAP1-/+: 94.1 vs 80.3%; p=0.0057), whereas it was significantly low in EPB41L5 group specific to wtEGFR cases (-/+: 85.1 vs 62.7%; p=0.017).
For DFS, all molecules were the significant recurrent factors specific to mEGFR cases (Grb2/ GEP100/ Arf6/ AMAP1/ EPB41L5; p=0.0023/ 0.0033/ 0.0411/ 0.0023/ 0.0263), whereas no molecule was significant specifc to wtEGFR cases.
Multivariate analyses specific to mEGFR cases showed that Grb2 and AMAP1 were the independent prognostic factors for OS and Grb2 was the only independent recurrent factor.
Conclusion
Arf6-related invasive pathway was significantly associated with poor prognosis specific to mEGFR adenocarcinoma. Grb2 and AMAP1 were the strong worsening effectors on the prognosis. Inhibition of this pathway should be a novel targeted therapy in mEGFR lung adenocarcinoma.
-
+
P2.17 - Treatment of Early Stage/Localized Disease (ID 189)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
-
+
P2.17-26 - Indocyanine Green Virtual Assisted Lung Mapping (ICG-VAL-MAP): Anyone Can Perform a Successful Preoperative Marking for a Small Lung Nodule (Now Available) (ID 2320)
10:15 - 18:15 | Author(s): Toshi Menju
- Abstract
Background
As a preoperative marking of small pulmonary nodules, we developed Virtual Assisted Lung Mapping (VAL-MAP), which is consisted of preoperative simulation using three-dimensional CT images and transbronchial dye marking using indigocarmine (IC). Between 2012 and 2016, we performed VAL-MAP in more than 200 cases in a single institution; however, we sometimes came across a situation, in which an identification of marked IC was difficult at post-marking CT and/or during surgery. Herein, we have developed a new VAL-MAP (ICG-VAL-MAP) using indocyanine green (ICG) and contrast agent. The purpose of this study was to prospectively evaluate the visibility of newly-developed ICG-VAL-MAP in an identification of ICG at post-marking CT as well as during surgery.
Method
Between January in 2017 and February in 2019, we performed ICG-VAL-MAP, using ICG and contrast agent in addition to IC as a marker for preoperative nodule identification, in 88 patients at our institution. Preoperative marking was performed on the same day as surgery or 1 day before surgery. During surgery, fluorescence endoscope system was used for identification of marked ICG.
Result
Targeted lesions were 105 nodules with the diameter ranging from 2 to 38 mm (median 8 mm). The depth of the lesion from the pleural surface ranged from 0 to 49 mm (median 8 mm). Total marking numbers were 208 (IC: 99, ICG: 109). At post-marking CT, IC was easily identified in 78 markings (78%), difficult to be identified in 10 markings (10%), and unable to be identified in 11 markings (11%). On the other hand, ICG was easily identified in all markings at post-marking CT. During surgery, IC was easily identified in 74 markings (74%), slightly identified in 4 markings (4%), and unable to be identified in 21 markings (21%). On the other hand, ICG was easily identified in 108 markings (99%) during surgery. Only in 1 case, ICG marking was accidentally placed far from a pleural surface, but ICG was slightly identified in a collapsed lung during surgery. In summary, ICG was significantly easily identified than IC during surgery (P<0.0001) as well as at post-marking CT (P=0.0002). There were no significant perioperative complications related to ICG-VAL-MAP. All nodules were identified intraoperatively and an appropriate surgical resection was conducted in each patient. In details, 53 wedge resections, 48 segmentectomies and 2 lobectomies were performed. Furthermore, all nodules were diagnosed pathologically (74 primary lung cancer, 24 metastatic lung cancer, and 7 benign nodule).
Conclusion
We confirmed that ICG-VAL-MAP was a novel and promising technique with better visibility than conventional VAL-MAP for the complete resection of small pulmonary nodules.
