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Alexander Marx



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    P1.14 - Thymoma/Other Thoracic Malignancies (Not CME Accredited Session) (ID 946)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.14-11 - The Expression Pattern of Programmed Death-Ligand 1 According to the Pathological Type of Malignant Thymic Epithelial Tumors (ID 12665)

      16:45 - 18:00  |  Author(s): Alexander Marx

      • Abstract
      • Slides

      Background

      Malignant thymic epithelial tumors (TETs) have pathological types ranging from low-grade to high-grade malignancy, while the pattern of PD-L1 expression remains unclear. We investigated PD-L1 expression in TETs and verified the pattern of expression associated with the pathological type.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We examined 66 malignant TETs. Immunohistochemical evaluation of PD-L1 expression was performed using anti-PD-L1 antibody (SP263). We calculated the tumor cell positive rate (Total Proportion Score: TPS) of PD-L1 expression. The discrimination of the tumor region was confirmed by immunostaining with anti-pan-cytokeratin antibody (AE1AE3). PD-L1 expression was examined for each type of histological classification of TETs. We classified a High TPS group (H group) and Low TPS group (L group) using a TPS cut-off value of 25% and examined the correlation with clinical background and prognosis. We classified Type B2, B3, and thymic carcinomas into a high-malignancy group. PD-L1 expression was also digitally analyzed based on Whole Slides Imagings (WSI) for objective analysis as Digital TPS.

      4c3880bb027f159e801041b1021e88e8 Result

      We identified WHO histological types (Type A/AB/B1/B2/B3/metaplastic tumor/thymic carcinomas = 8/19/5/15/6/2/11). In Type A, PD-L1 expression was low in most cases and the median of TPS was 22%. In Type AB, Type A and B regions showed low and high TPS, respectively, and the median was 23%. In Type B1, TPS was low in most cases and the median was 26%. In Type B2, TPS was higher than that in Type B1, and the median was 69%. In Type B3, TPS was high (>50%) in all cases and the median was 86%. The PD-L1 expression of thymic carcinomas ranged from low to high and the median was 28%. Metaplastic tumors showed scanty PD-L1 expression. The High PD-L1 group showed more advanced disease stages according to the Masaoka stage and TMN classification, and the TPS of Type B2 and B3 was significantly higher than that of Type A, AB and B1. The disease-free survival rate was significantly lower in the H group than that in the L group. When we examined the prognosis in high-malignancy group, there were no significant differences in the disease-freel and overall survival rates by TPS. Based on measurements using WSI, Digital TPS correlated with visual TPS (correlation coefficient=0.85,pvalue<0.001).

      8eea62084ca7e541d918e823422bd82e Conclusion

      TETs had the characteristic features of the PD-L1 expression according to histological types. Type B2 and B3 thymomas was higher PD-L1 expression than the other types of TETs.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.14-12 - GTF2I Mutation in Thymomas: Indian and German Study (ID 14314)

      16:45 - 18:00  |  Author(s): Alexander Marx

      • Abstract
      • Slides

      Background

      Point mutation (L404H) of GTF2I gene on chromosome 7 has been identified in thymic epithelial tumors; most predominantly in A and AB histotypes and associated with good prognosis. The objective of this retrospective analysis was to assess the frequency of GTF2I mutation in Indian and German thymomas and correlate with WHO histotypes.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A cohort of Indian and German thymomas of different histotypes was retrieved from the archives. Clinicopathological details were obtained from case files. Hematoxylin-eosin stained slides were reviewed and histopathological subtypes along with Masaoka-Koga staging were determined. The available blocks were selected for DNA extraction. Tumors rich in cancer cells (>50%) were evaluated for GTF2I mutation using Sanger sequencing. Primer for Exon 15 of GTF2I gene was designed using NCBI and Primer 3 (v.0.4.0) software. Results were compiled and analysed.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 126 resection specimens were retrieved comprising 23 (18.2%) Type A, 30 (23.8%) Type AB 16 atypical A/AB (12.6%) and 30 (23.8%) Type B thymomas. Remaining 27 cases belonged to 18 thymic carcinomas, 2 sclerosing mediastinitis, 2 metaplastic thymomas, 1 thymolipoma, and 4 non-thymomatous lesions.

      Out of a total of 69 A/AB thymomas, 53 (76.8%) were positive including 88% (22/25) Indian and 65.9 % (29/44) German cases. 26% (18/69) A/AB were negative. All Indian B histotypes (n=9) were negative, whereas 4 German B thymomas (4/21; 19%) were positive for GTF2I mutation. No mutations were found in non-thymomatous pathologies.

      Among 34 Indian cases, there was equal gender distribution, median age was 48 years and 31 were in lower stage groups (Stage I and II). Clinical details and follow up available in 17 of 34 cases had a median follow up of 14 months and revealed presence of myasthenia gravis in 76.5% cases. Recurrence seen in 3 cases revealed high risk morphology (2 Type B histotypes and 1 atypical A) and one death of Type A was due to myasthenic crisis.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The similarity of Indian and German (and previously published American) cohorts of A/B and type B thymomas in term of GTF2I mutation frequencies suggests a thymus-specific microenvironmental mutagenic mechanism and argues against a relevant impact of environmental or ethnic (germ line) factors. The unusually high prevalence of Myasthenia gravis among the Indian thymomas warrants further analysis to exclude referral bias.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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