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S. Sakashita
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P2.02 - Biology/Pathology (ID 616)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 2
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.02-025 - Histological Difference of Tumor-Infiltrate Lymphocytes in Non-Small Cell Lung Cancer (ID 7506)
09:30 - 09:30 | Author(s): S. Sakashita
- Abstract
Background:
Lymphocytes play important roles in cancer immunity. Tumor-infiltrate lymphocytes (TILs) are seen in non-small cell lung cancer (NSCLC) and generally classified according to their localization (epithelial area and stromal area). The distribution and the number of TILs are quite different. Cancer cells have an ability to evade from cancer immunity, and the several mechanisms of the ability have been reported; decreased expression of tumor antigen, inhibition of immune response, induction of immunosuppressive cells, and secretion of immunosuppressive cytokines. We hypothesized that the mechanisms of evasion from cancer immunity would influence TIL representation. In this study, we investigated the differences of TILs in histological differentiation, since we considered that histological difference could affect cancer immunity.
Method:
We retrospectively investigated surgical specimens between 2009 and 2015. Consecutive 20 cases with minimally invasive adenocarcinoma (MIA), lepidic adenocarcinoma (Ad lepidic), acinar or papillary adenocarcinoma (Ad aci/pap), solid adenocarcinoma (Ad solid) and squamous cell carcinoma (Sq) were selected (total 100 cases). We checked all fields of the tumors in the slice with maximum tumor-diameter microscopically at 100-fold magnification. TILs in the field were judged as positive when more than 10 lymphocytes flocking in tumor epithelial area or stromal area were observed. TILs of the tumors were assessed as the rate of the TIL positive fields in all, and separately evaluated in epithelial area and stromal area. Then, analysis of variance was used to assess the histological differences of TILs. Significant difference was considered as p-value was less than 0.05.
Result:
The average rates of TIL positive fields in epithelial area of MIA, Ad lepidic, Ad aci/pap, Ad solid and Sq were 11.2 ± 20.4%, 15.8 ± 20.4%, 26.9 ± 20.9%, 52.4 ± 30.0% and 27.8± 28.8%, respectively. The rate of Ad solid was significantly higher than those of MIA, Ad lepidic and Ad aci/pap, and the rate of Sq was also significantly higher than those of MIA and Ad lepidic. The average rates of TIL positive fields in stromal area of MIA, Ad lepidic, Ad aci/pap, Ad solid and Sq were 41.9 ± 26.1%, 51.2 ± 28.3%, 57.6 ± 23.2%, 67.7 ± 25.4% and 67.8 ± 30.0%, respectively. The rate of MIA was significantly lower than Ad solid and Sq.
Conclusion:
TILs were significantly different representation depending on the histology. Especially in adenocarcinoma, the TILs differed according to the grade of differentiation. These results might show that highly differentiated lung adenocarcinoma has low expression of tumor antigen.
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P2.02-073 - Cytoplasmic Mislocalization of ECT2 Protein Is Associated with Poor Prognosis in Lung Adenocarcinoma (ID 8430)
09:30 - 09:30 | Author(s): S. Sakashita
- Abstract
Background:
Lung cancer is the most lethal malignancy in worldwide. We have previously compared genetic abnormality profiles in early-stage lung adenocarcinoma using array-comparative genomic hybridization (CGH) and found that Epithelial cell transforming sequence 2 (ECT2) amplification and overexpression a new prognostic marker in early-stage lung adenocarcinoma (Cancer Science, 2014). ECT2 is an oncogene that is overexpressed in several types of human cancer and has tumorigenic activity. ECT2 is localized in the nucleus of normal cells, and its function is associated with cytokinesis. In cancer cells, ECT2 exists in not only nucleus but also cytoplasm. However, cytoplasmic ECT2 is thought to promote tumor growth and invasion. In the present study, we aimed to explore the expression of cytoplasmic ECT2 and to assess its functional and prognostic significance in lung adenocarcinoma. First, we examined the subcellular localization of the ECT2 protein in lung adenocarcinoma cells. Subsequently, we investigated the biological significance of cytoplasmic ECT2 that mediated its phosphorylation state. Finally, we examined the clinicopathological attributes of cytoplasmic ECT2 in terms of patient outcome.
Method:
ECT2 expression was evaluated in an immortalized lung epithelial cells (PL16B) and eight lung adenocarcinoma cell lines Calu-3, A549, RERF-LC-KJ, NCI-H1650, PC-9, NCI-H23, NCI-H1975, and HCC827 using Immunoblotting, RT-PCR, Immunofluorescence, and Immunohistochemistry. In order to assess the clinicopathologic characteristics of cytoplasmic ECT2, we examined 50 cases of surgical specimens lung adenocarcinoma by immunohistochemistry. Twenty fresh scraping samples of lung adenocarcinoma were also used to evaluate the expression of Phosho-ECT2 (T790). The Kaplan–Meier method and Cox regression analyses represent the prognostic significance of cytoplasmic ECT2 in lung adenocarcinoma.
Result:
We found that ECT2 expressed in eight lung adenocarcinoma at variable degree levels. In PL16B cells, ECT2 was localized in the nucleus, whereas in lung adenocarcinoma cell lines ECT2 distributed in both the cytosol and the nucleus. Importantly, overexpression of ECT2 leads to aberrant cytoplasmic localization in lung adenocarcinoma cells. We also found that cytoplasmic ECT2 was phosphorylated and accumulated at the cell membrane in lung adenocarcinoma cell lines and surgical specimens. The phosphorylated form of ECT2 was reported to correlate with malignant attributes of lung adenocarcinoma and our clinical analysis showed that cytoplasmic ECT2 expression was significantly associated with poor outcome (OS; P=0.002, DFS; P =0.001), and was an independent prognostic factor in lung adenocarcinoma.
Conclusion:
We demonstrate that aberrant localization of ECT2 to the cytoplasm is a specific feature of lung adenocarcinoma, and provide a new potential prognostic biomarker in lung adenocarcinoma.
