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Misa Noguchi



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    P1.04 - Immunooncology (Not CME Accredited Session) (ID 936)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.04-06 - Clinicopathological Analysis of Pulmonary Pleomorphic Carcinoma (ID 12488)

      16:45 - 18:00  |  Presenting Author(s): Misa Noguchi

      • Abstract
      • Slides

      Background

      Pulmonary pleomorphic carcinoma (PC) is a histological type of poorly differentiated non-small cell lung carcinoma (NSCLC) which consists of both sarcomatous and carcinomatous components. Except for its aggressive behavior and resistance to chemoradiotherapy, clinicopathological characteristics remain elusive due to its rarity. Recently, immunotherapy targeting the programmed death-1 (PD-1)/PD ligand 1 (PD-L1) pathway has demonstrated favorable clinical outcomes in NSCLC. However, the expression patterns of PD-L1 in pulmonary PC are still unknown. We reviewed the results of clinicopathological characteristics and PD-L1 expression of 46 cases of pulmonary PC resected in our institution.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Forty-six patients with pulmonary PC consecutively underwent lung resections for the treatment in our institution between 2002 and 2017. Various clinical and pathological data were reviewed retrospectively to analyze prognostic factors for overall survival (OS) after surgery. OS was compared among patient groups by log-rank tests. For multivariate analyses, Cox hazard models were applied. P-value less than 0.05 was considered significant. Tissue samples were collected from the paraffine-embedded tumor blocks of these patients. Then, PD-L1 expression levels of the tumor were examined by immunohistochemical staining method using anti PD-L1 antibody (clone 28-8).

      4c3880bb027f159e801041b1021e88e8 Result

      Patients were 40 male and 6 female, and their median age was 68 years (range: 36 to 83 years). The majority of patients with pulmonary PC were smokers (87.0%, 40/46). Forty-five tumors contained identifiable carcinomatous components, and the other 1 consisted of only spindle cell component. An adenocarcinoma component was found in 27 cases, a squamous cell carcinoma component in 5, and the other components in 14. OS rate was 50.8% at 5 years. Univariate analysis revealed that tumor size over 3 cm, the presence of necrosis and pathological T factor were significantly associated with poorer overall survival. Lymphatic invasion was not statistically significant, but tended to be associated with poorer overall survival. Multivariate analysis showed that lymphatic invasion tended to be associated with poorer overall survival.

      PD-L1 was highly expressed in pulmonary PC (62.5%, 10/16). The proportion of PD-L1 expression was significantly higher in the sarcomatous component than in the carcinomatous component.

      8eea62084ca7e541d918e823422bd82e Conclusion

      We found that lymphatic invasion suggested a worse prognosis for resection of pulmonary PC. Moreover, our study demonstrates that pulmonary PCs very frequently express PD-L1. Thus, targeting the PD-1/PD-L1 pathway may represent a potential therapeutic candidate for this aggressive tumor especially in its sarcomatous component.

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    P2.03 - Biology (Not CME Accredited Session) (ID 952)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.03-29 - Prognostic Significance of Phosphorylated Fyn in Patients with Lung Adenocarcinoma (ID 12824)

      16:45 - 18:00  |  Author(s): Misa Noguchi

      • Abstract

      Background

      Src family tyrosine kinases, including Fyn, are non-receptor tyrosine kinases and they are known to drive malignancy in various kinds of cancers. Some papers have reported that Fyn is an effector of EGFR signaling. Additionally, Fyn is recognized as an additional therapeutic target. However, little is known about the clinical importance of phosphorylated Fyn (pFyn) in lung adenocarcinoma. The purpose of the present study is to clarify the prognostic significance of pFyn in lung adenocarcinoma.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A total of 251 lung adenocarcinoma specimens were collected from patients who underwent surgery in our institute. Tissue microarrays (TMA) were assembled from paraffin-embedded tumor blocks. We analyzed pFyn expression through immunostaining of TMA and classified them as 0, +1, +2, +3. The association between pFyn expression as well as the patients’ clinical information was statistically analyzed. Correlations were compared using Pearson's chi-square test and overall survival (OS) were compared using the log-rank test after propensity score matching (age, gender, smoking history, pathological stage, EGFR mutation status, and p53 mutation status). The Institutional Review Board approved this study and informed consent for tumor tissue usage was obtained pre-operatively.

      4c3880bb027f159e801041b1021e88e8 Result

      Unadjusted pathologic stage distributions by TNM classification (WHO, 7th edition) were as follows: Stage 1A: 128 patients, Stage 1B: 73, Stage 2A: 23, Stage 2B: 4, Stage 3A: 23. pFyn was positive in 118 cases (47.6%). There was a significant correlation between pFyn expression and gender, pathological stage, p53 mutation status, and poor OS. The propensity score adjusted analysis revealed that the prognosis of pFyn positive group was significantly worse compared to the pFyn negative group (p=0.046), which was observed only in the patients with mutant EGFR.

      pfyn.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      pFyn expression may affect the prognosis of patients with lung adenocarcinoma in a EGFR mutation dependent manner.

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    P2.09 - Pathology (Not CME Accredited Session) (ID 958)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.09-23 - A Combination of Podoplanin and E-Cadherin Expression in Lung SqCC may be a Poor Prognostic Indicator: A Propensity Score-Matched Analysis. (ID 12889)

      16:45 - 18:00  |  Author(s): Misa Noguchi

      • Abstract
      • Slides

      Background

      The combination of clinicopathological prognostic factors for lung squamous cell carcinoma (SqCC) has not been still advocated. The aim of this study is to analyze the combination of prognostic markers of SqCC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Retrospective chart review was performed to identify patients undergoing resection for SqCC between 2003 and 2015 (Ethical approval #: E2235). We examined the expressions of E-cadherin, vimentin, and podoplanin in cancer cells on tissue microarray to evaluate their prognostic value. Survival outcomes were analyzed with Kaplan-Meier method and log-rank test. To eliminate selection bias, propensity score-matched analysis on the basis of clinicopathological factors was performed.

      4c3880bb027f159e801041b1021e88e8 Result

      Two hundred and two patients underwent complete resection with curative intent were identified (Median follow-up: 50.0 months, range: 0.67-150, 5y-OS: 67.5%, 5y-DFS: 53.4%). There was no significant difference in the prognosis of patients with low E-cadherin expression alone (OS: p=0.242 and DFS: p=0.401) and podoplanin-positive alone (OS: p=0.389 and DFS: p=0.874). However, OS and DFS in the combination of podoplanin-positive and low E-cadherin expression group was significantly lower than those in another group (OS; 75.0% vs 57.0%, respectively, p=0.034, DFS; 65.2% vs 44.2%, respectively, p=0.031.).

      figure_12889.tif

      8eea62084ca7e541d918e823422bd82e Conclusion

      A combination of podoplanin-positive and low E-cadherin expression in lung SqCC may be a poor prognostic indicator.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P3.09 - Pathology (Not CME Accredited Session) (ID 975)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.09-13 - Molecular Profiling Suggests the Different Mechanisms Among Local Invasiveness in Resected Human Lung Adenocarcinoma (ID 14060)

      12:00 - 13:30  |  Author(s): Misa Noguchi

      • Abstract

      Background

      Local invasive factors are pathologically defined as pleural or lymphovascular invasion in lung cancer. Accumulating evidences have shown that these factors are associated with metastatic activity finally leading to poor survival of the patients. Here we examined the correlations of cancer-progressive molecular markers with local invasiveness in resected human adenocarcinoma.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Clinical samples were obtained from the 256 cases of lung adenocarcinoma which were consecutively operated to treat from January 2001 to December 2007 in our institution. Pathological stage distribution of the cases by TNM classification was below: 1A: 118, 1B: 71, 2A: 22, 2B: 4, 3A: 23, 3B: 1, 4:17.

      Tissue microarrays were immunohistochemically (IHC) stained. The previously published IHC data of molecular markers and DNA mutation data of EGFR and K-ras using our same cohorts were integrated. These markers included TP53, E-cadherin, vimentin, TWIST, CD133, CD44, Aldehyde dehydrogenase (ALDH), Carbonic anhydrase (CA)-9, Lactate dehydrogenase (LDH)-A, Glucose transporter (GLUT)-1, Hypoxia inducible factor (HIF) 1α, Ubiquitin C-terminal hydrolase (UCH)-L 1, Grb2, GEP100, Arf6, AMAP1, EPB41L5, phosphorylated receptor tyrosine kinases (EGFR, HER2, cMet, VEGFR2).

      Statistical analyses were performed by chi-square test or log-rank test. For survival data analyses, stage4 cases were excluded.

      4c3880bb027f159e801041b1021e88e8 Result

      Positive rates for these markers were from 9.6~63.4% as shown in the table.

      The most significant correlations with pleural, lymphatic, and vascular invasion were found in EPB41L5 (p=0.0005), LDH-A (p<0.0001), and, p53 (p<0.0001) and GLUT-1 (p<0.0001), respectively.

      The probable markers predicting both the nodal metastases and the occurrence of events were associated with EMT, glycolytic, hypoxia, and Arf6-related pathways.

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      8eea62084ca7e541d918e823422bd82e Conclusion

      The pivotal markers were different among the types of local invasiveness. Pathways commonly used in local invasiveness, nodal and distant metastases were suggested to be EMT, glycolysis, hypoxia-related.

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