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S.B. Yoo



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    P1.10 - Poster Session 1 - Chemotherapy (ID 204)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.10-003 - Alteration of the E-cadherin/β-catenin complex predicts poor response to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment (ID 161)

      09:30 - 09:30  |  Author(s): S.B. Yoo

      • Abstract

      Background
      Epidermal growth factor receptor (EGFR) mutation alone may be insufficient to predict clinical outcomes in the response to EGFR-tyrosine kinase inhibitor (TKI) therapy. The secondary mutation T790M and MET amplification are mechanisms of acquired resistance to EGFR-TKI in approximately 50% of patients, but the remaining mechanisms are unknown.

      Methods
      Eight metastatic lesions and specimens from 41 non-small cell lung carcinoma (NSCLC) patients harbouring activating EGFR mutations who underwent surgical resection and EGFR-TKI therapy were available. Immunohistochemistry was used to evaluate E-cadherin, β-catenin, and PTEN. Chromogenic in situ hybridisation and silver-enhanced in situ hybridisation were used to evaluate EGFR and MET amplification.

      Results
      Patients with E-cadherin/β-catenin alteration showed a poor objective response rate (ORR) (p=0.005) and shorter overall survival (p=0.059). Additionally, β-catenin alteration was associated with a poor ORR (p=0.012). In the metastatic tumours, 3 cases (37.5%) showed the acquisition of altered E-cadherin/β-catenin and PTEN loss, and 2 cases (25.0%) demonstrated MET/EGFR amplification.

      Conclusion
      Altered E-cadherin/β-catenin expression in NSCLC harbouring EGFR mutations was associated with a poor response to EGFR-TKI. During metastatic progression, changes in E-cadherin/β-catenin were found. These results may suggest that E-cadherin/β-catenin alteration is related to poor TKI response and resistance.

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    P2.18 - Poster Session 2 - Pathology (ID 176)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 1
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      P2.18-002 - A comprehensive comparative analysis of the histomorphological features of ALK-rearranged lung adenocarcinoma based on driver oncogene mutations : frequent expression of epithelial-mesenchymal transition markers than other genotype (ID 221)

      09:30 - 09:30  |  Author(s): S.B. Yoo

      • Abstract

      Background
      Molecular classification of lung cancer correlates well with histomorphologic features. However, detailed histomorphologic features which differentiate ALK rearranged tumors from ALK wild type has not been fully evaluated. To investigate histomorphologic features of tumors harboring ALK rearrangement to evaluate the predictive significance of morphologic characterization, we compared the histomorphological analysis between ALK-rearranged and ALK negative lung adenocarcinomas based on driver oncogene mutations.

      Methods
      Eighty resected ALK rearranged lung adenocarcinomas and two hundred thirteen resected ALK negative adenocarcinomas (91 EGFR mutated, 29 K-ras mutated and 93 triple-negative) were analyzed for several histomorphological parameters and histologic subtype based on newly proposed IASLC/ATS/ERS classification.

      Results
      ALK rearranged tumors were associated with a younger age at presentation, frequent nodal metastasis and higher stage at diagnosis, compared with patients with other genotypes. ALK rearranged tumors were more likely to show solid predominant pattern (43.8%, 35/80) than other genotypes (p<0.001) and a lepidic predominant histology was not observed in ALK rearranged tumors (p<0.001). In ALK rearranged tumors, considerable number of the tumors (67.5% , 54/80) contained at least 5% solid pattern but only small number of the tumors (12.5%, 12/80) contained at least 5% lepidic pattern, compared with other genotypes (p<0.001). The most significant morphological features distinguishing ALK rearranged tumors from ALK negative tumors were cribriform formation (OR: 3.253, p=0.028), presence of mucin-containing cells (OR: 4.899, p=0.008), close relation to adjacent bronchioles (OR: 5.361, p=0.001), presence of psammoma body (OR: 4.026, p=0.002) and solid predominant histological subtype (OR: 13.685, p=0.023). ALK-rearranged tumors exhibited invasive histomorphological features, aggressive behavior and frequent expression of epithelial-mesenchymal transition markers (loss of E-cadherin and expression of vimentin) compared with other genotype (p =0.015). Spatial proximity between bronchus and ALK-rearranged tumors and frequent solid histologic subtype with p63 expression may cause diagnostic difficulties to differentiate squamous cell carcinoma in the small biopsy, whereas p40 was rarely expressed in ALK-rearranged adenocarcinoma.

      Conclusion
      Knowledge of these features may improve the diagnostic accuracy and lead to a better understanding of the characteristic behavior of ALK-rearranged tumors.