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S. Watanabe
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P1.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 224)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.08-028 - PD-L1 Expression in Neuroendocrine Tumors of the Lung (ID 2217)
09:30 - 17:00 | Author(s): S. Watanabe
- Abstract
Background:
The World Health Organization (WHO) classification recognizes four major types of neuroendocrine tumors of the lung: typical carcinoid, atypical carcinoid, small cell lung cancer (SCLC), and large-cell neuroendocrine carcinoma (LCNEC). These diagnostic categories have different prognostic implications and require distinct treatment strategies. The PD-1/PD-L1 pathway is a major target of anti-tumor immunotherapy. PD-L1 expression has been reported to cause local immune suppression and is considered as a predictive marker of immune checkpoint therapeutics. In order to clarify any differences in the expression of PD-L1 according to the type of neuroendocrine tumor in the lung, we investigated the expression levels of PD-L1 by immunohistochemistry in neuroendocrine tumors of the lung.
Methods:
The subjects of this study were patients who were diagnosed as having lung neuroendocrine tumors and were treated at the National Cancer Center Hospital from 1982 to 2010. A tissue microarray (TMA) made from the surgical specimens was analyzed. After the rabbit monoclonal PD-L1 antibody was validated (clone E1L3N, Cell Signaling Technology, Danvers, MA), the TMA was stained and the tumor PD-L1 expression score was calculated by a semiquantitative method (by multiplying the intensity [0–3] by the staining area [0–100%]). To determine the PD-L1 expression, 3 (1%) was used as the cutoff score.
Results:
A total of 227 patients were included in this study. The characteristics of the entire patient population were as follows; median age, 65 years (range: 19-84 years); gender, male 168 (74.0%) / female 59 (26.0%); smoking status, smokers 191 (84.1%)/non-smokers 36 (15.9%); pStage: IA 79 (34.8%)/IB 36 (15.9%)/IIA 25 (11.0%)/IIB 29 (12.8%)/IIIA 47 (20.7%)/IIIB 6 (2.6%)/IV 5 (2.2%); histology, typical carcinoid 46 (20.3%)/atypical carcinoid 6 (2.6%)/SCLC 69 (30.4%)/LCNEC 106 (46.7%). Of the 227, samples from 15 (6.6%) showed positive staining for PD-L1. The characteristics of the patients showing positive staining for PD-L1 were as follows; median age, 71 years (range: 37-84 years); gender, males 12 (7.1%)/females 3 (5.1%); smoking status, smokers 13 (6.8%)/non-smokers 2 (5.6%); pStage, IA 3 (3.8%)/IB 2 (5.6%)/IIA 2 (8.0%)/IIB 5 (17.2%)/IIIA 2 (4.3%)/IIIB 0 (0%)/IV 1 (20.0%); histology, typical carcinoid 0 (0%)/atypical carcinoid 0 (0%)/SCLC 4 (5.8%)/LCNEC 11 (10.4%). In 31 of the 69 cases of SCLC who were treated by surgery, the disease recurred; of these 31 patients who developed disease recurrence, positive expression for PD-L1 was noted in 2 patients (6.5%). Furthermore, the disease recurred in 33 of the 106 cases of LCNEC treated by surgery; of the 33, 2 (6.1%) showed expression of PD-L1.
Conclusion:
None of the tumors in the patients with typical or atypical carcinoid in our study showed expression of PD-L1. Only the tumors in 4 of the 69 patients (5.8%) with SCLC and 11 of the 106 patients (10.4%) with LCNEC showed positive staining results for PD-L1. The data suggest that drugs directed against PD-1/PD-L1 might be potentially useful in the immunotherapy of SCLC and LCNEC.
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-110 - PTPRH Hypomethylation as a Prognostic Factor in Non-Small Cell Lung Cancer (ID 759)
09:30 - 17:00 | Author(s): S. Watanabe
- Abstract
Background:
Tyrosine phosphorylation is an important signaling mechanism in cancer. PTPRH is a receptor-type protein tyrosine phosphatase thought to be a potential regulator of tumorigenesis. The aim of this study is to clarify the significance of PTPRH expression and its regulation by DNA methylation in non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma.
Methods:
PTPRH mRNA expression was examined in 89 NSCLC and corresponding non-cancerous tissues. The correlation between DNA methylation and PTPRH gene expression was investigated in another cohort that consisted of 145 patients with lung adnocarcinoma. Gene regulation by DNA methylation was assessed using a DNA methylation inhibitor. Statistic analysis was performed to clarify whether the DNA methylation status of PTPRH is a prognostic factor for patients with lung adenocarcinoma.
Results:
PTPRH mRNA expression was significantly up-regulated in NSCLC. PTPRH DNA methylation was reduced in lung ademocarcinomas and inversely correlated with mRNA expression. 5-aza-2'-deoxycytidine treatment of lung cancer cell lines with low PTPRH expression, restored mRNA PTPRH expression levels. Furthermore, low PTPRH methylation was associated with shorter recurrence-free survival (P < 0.0002) and overall survival (P < 0.0001). Multivariate analysis revealed that PTPRH DNA methylation was an independent prognostic factor (P < 0.01).
Conclusion:
We confirmed that PTPRH is overexpressed in NSCLC. In addition, we determined that hypomethylation of PTPRH is a poor prognostic factor in lung adenocarcinoma.
