Virtual Library

Start Your Search

Anja C Roden



Author of

  • +

    GR01 - Thymic Malignancies Tumor Board (ID 777)

    • Event: WCLC 2018
    • Type: Grand Rounds Session
    • Track: Thymoma/Other Thoracic Malignancies
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 10:30 - 12:00, Room 206 F
    • +

      GR01.01 - Pathology (ID 11386)

      10:30 - 10:45  |  Presenting Author(s): Anja C Roden

      • Abstract

      Abstract not provided

  • +

    MA24 - Genomic Evolution, KEAP 3 and More Non-Coding RNA (ID 928)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Biology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 10:30 - 12:00, Room 205 BD
    • +

      MA24.02 - Genomic Alterations in Lung Adenocarcinoma Precursor Lesions (ID 13037)

      10:35 - 10:40  |  Author(s): Anja C Roden

      • Abstract
      • Presentation
      • Slides

      Background

      Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are thought to be precursor lesions of invasive disease. Genomic alterations in these lesions have not been described.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Genomic analysis including whole genome and exome sequencing, and SNP array analysis were performed on 9 AIS and 18 MIA pathologically confirmed samples to identify single nucleotide variants (SNVs), structural variations and copy number variations. Mutation significance and signature analysis were determined by MutSig and NMF analyses. Pathway analysis was performed using ingenuity IPA.

      4c3880bb027f159e801041b1021e88e8 Result

      The range of mutation burden for AIS and MIA was 0.7 to 12/Mb with a median of 1.7/Mb. This compared to a mean of 7.2/Mb for invasive lung adenocarcinoma. Significantly mutated genes identified in AIS and MIA were ELAVL4, LIN37, XCL1, ELK3, RPS9, FBXO2, HLA-B and MYOG, which affected pathways regulating ESR1, ELAVL1 and TP53. Genes with recurrent mutations included MTPN, CDC27, GGT2, CTBP2, EGFR, NCOR1 and TGIF1 and implicated EGFR, MYC and MAPK1 pathways. Somatic mutations were characterized by C>T and T>C transition signature, whereas CNV analysis found high concentrations of copy number amplifications at 6p21.3 to 6p22.1, 8q24.12 to 8q24.3 and at 21q22.3. There were comparable structural variations in the AIS cases compared to MIA.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In contrast to hypothesized models of tumor progression, AIS and MIA can harbor significant genomic alterations and tumor mutation burden. These observations challenge the notion of accumulating mutation burden during the progression to invasive disease. The finding of high mutation burden in some of these precursor lesions also suggests the intriguing concept of immunotherapeutic options for either treatment or chemoprevention.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    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
    • +

      P3.09-05 - Significance of the Expression of PD-L1/PD-1 by Tumoral and Immune Cells in Non-Small Cell Lung Cancer.  (ID 14241)

      12:00 - 13:30  |  Author(s): Anja C Roden

      • Abstract
      • Slides

      Background

      Non-Small Cell Lung Cancer (NSCLC) accounts for approximately 85% of all cases of lung cancer, including adenocarcinoma, squamous cell carcinoma and large cell carcinoma. There is solid evidence that demonstrates the existence of anti-tumor adaptive T-cell mediated immunity activation in lung tumors, indicating that lung cancers are immunogenic. PD-L1and PD-1 expression level in lung cancer may be a predictive biomarker for the use of PD1/PD-L1 inhibitors. However, the reproducibility of PD-L1 staining using different antibodies and platforms is still a matter of debate. We assessed whether PD-L1 expression in non-small cell lung cancer is associated with specific clinical features or survival using four different antibodies and if the expression of PD-1 in TILs correlates with the expression of PD-L1 in same group of cells.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      PD-L1 and PD-1 status was assessed with IHC (AB clone SP142 and SP263 - Ventana, 22C3, 28-8 – Dako and PD-1) on archival FFPE surgical tumor specimens, arrayed on tissue microarrays (TMAs) with duplicate 1 mm cores, from Karolinska University Hospital. All patients (n = 598) underwent curative surgery between 1987 and 2015. The following cases were excluded from survival analysis (n = 89): R1 resection, early post-operative mortality, adjuvant chemo- or radiotherapy. PD-L1 staining was scored as positive if present in > 1% of tumor cells, independently of staining intensity.

      4c3880bb027f159e801041b1021e88e8 Result

      Patient and tumor characteristics were as follows. Median age (IQR): 68 years (27-89); gender: male/female 54%/46%; histology: squamous-cell carcinoma (SCC)/Non-squamous (N-Sq)-NSCLC/carcinoid 219 (32%)/394 (58%)/45(7%); p-stage: IA/IB/IIA/IIB/IIIA/IIIB 50%/26%/10%/10%/2%/0.2%. PD-L1 28-8 was positive in 11% of cases, Pearson Chi-square p<0.0001). PD-L1 positivity 22C3/SP263/SP142 was 10%/13%/3%. All carcinoids were negative for PD-L1. In NSCLC, PD-L1 positivity for each antibody was associated with tumor size (T1/T2-4; Fisher’s exact test, p<0.001) and grade of differentiation (G1, G2 and G3; p<0.0002). Statistically significant association between PD-L1 expression and OS was only observed using the clone SP263 (log-rank p=0.013). PD-1 expression in TILs correlates with those of PD-L1 (clone 28-8).

      8eea62084ca7e541d918e823422bd82e Conclusion

      In this surgical series, the clone SP142 showed less PD-L1 expression in the tumor cells. PD-L1 status was associated with tumor size, grading and only the clone SP263 showed association between its expression and survival ratio. PD-1 expression in TILs correlates with those of PD-L1.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.