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Cecilia Brambilla



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    MA12 - New Frontiers from Pathology to Genomics (ID 138)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Mesothelioma
    • Presentations: 1
    • Now Available
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      MA12.02 - Growth Patterns in Epithelioid Malignant Pleural Mesothelioma: A Clinicopathological Review of 614 Cases Over 15 Years (Now Available) (ID 1595)

      14:00 - 15:30  |  Author(s): Cecilia Brambilla

      • Abstract
      • Presentation
      • Slides

      Background

      Nuclear grading system has been validated as a powerful prognostic tool for epithelioid malignant pleural mesothelioma (MPM) whilst growth patterns had demonstrated prognostic value in earlier studies. We aim to externally validate the previous findings and evaluate the utility of a composite architecture-nuclear grade scoring system.

      Method

      We retrospectively reviewed 614 consecutive cases of epithelioid MPM diagnosed at our institution over a 15-year period. Clinicopathological information including predominant growth pattern (Solid, Tubulo-papillary, Trabecular, Micropapillary, Microcystic, Discohesive, Pleomorphic) and 2-tier nuclear grade were retrieved from an institutional mesothelioma database. The tumours were categorised into High Grade (Solid, Micropapillary, Score=1) and Low Grade (All others, Score=0). A composite score (0-2) was generated based on growth pattern and 2-tier nuclear grade (0-1). Survival analysis was performed using Kaplan-Meier method.

      Result

      Pleomorphic epithelioid MPM was associated with the worst median overall survival (5.4 months), followed by micropapillary- (6.2 months), solid- (10.5 months), microcystic- (15.3 months), discohesive- (16.1 months), trabecular- (17.6 months) and tubulo-papillary- (18.6 months) patterns. The composite scoring system further improved stratification of overall survival based on 2-tier nuclear grade (19.8 vs. 13.4 vs. 8.1 months, p<0.001).

      growth patterns (except cribriform_wdpm).jpg

      composite architecture-ng score v2.jpg

      Conclusion

      Epithelioid MPM growth patterns predicted survival in our cohort. Composite architecture-nuclear grade scoring system further improved prognostic stratification.

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    P1.04 - Immuno-oncology (ID 164)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.04-63 - Correlation of Mutations in TP53, CDKN2A and PIK3CA with VISTA Expression in Pleomorphic Lung Carcinoma (ID 2248)

      09:45 - 18:00  |  Author(s): Cecilia Brambilla

      • Abstract

      Background

      Pleomorphic Lung Carcinoma (PC) is a rare subtype of NSCLC poorly responsive to systemic therapy. VISTA is an immune checkpoint that negatively regulates T-cells and offers an alternative therapeutic approach to immune checkpoint manipulation. It has increased expression in the tumour microenvironment. We aimed to identify the genomic associations of PC with VISTA immunohistochemistry (IHC) expression and establish its correlation with PD-L1 IHC expression.

      Method

      Histopathological assessment and diagnosis was confirmed for 42 cases of resected PCs from the Royal Brompton Hospital histopathology diagnostic archive. DNA was isolated and a targeted capture panel for next generation sequencing performed. Samples were stained with H&E to confirm diagnosis, VISTA (D1L2G) and PD-L1 (28-8) and scored as the proportion of positively stained cells. Normal lung acted as control.

      Result

      VISTA was increased in tumour infiltrating immune cells compared to background lung and tumour (median: 33% (0-85) vs. 0% (0-15); vs. 0% (0-11); P<0.001). VISTA was upregulated on infiltrating immune cells of cases with variants in TP53 (n=25, median 52.5% vs. 24% P=0.008) and CDKN2A (n=4, median 57.5% vs. 30%; P=0.068) but was reduced in cases with PIK3CA mutations (n=4; median 7% vs. 35%; P=0.029). There was no association of VISTA with PD-L1 expression (spearman rank: -0.19; P=0.22).

      Figure 1: Percent of VISTA staining of immune cells according to tumour mutation

      figure1a.png

      Conclusion

      VISTA is raised in infiltrating immune cells of tumours with TP53 and CDKN2A mutations. This may suggest dampening of the immune reaction to tumours defective in cell cycle control. Conversely, tumours with PIK3CA mutations had reduced VISTA expression by infiltrating immune cells. VISTA and PD-L1 exhibited no association in their levels of expression and therefore offers a therapeutic opportunity.

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    P1.06 - Mesothelioma (ID 169)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Mesothelioma
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.06-08 - WDPM-Like but Not Cribriform as Secondary Growth Patterns Modify Survival in Epithelioid Malignant Pleural Mesothelioma (ID 1609)

      09:45 - 18:00  |  Author(s): Cecilia Brambilla

      • Abstract
      • Slides

      Background

      The presence of well differentiated papillary mesothelioma (WDPM)- like and cribriform growth patterns in otherwise unequivocally invasive, tubulo-papillary-predominant epithelioid malignant pleural mesothelioma (MPM) is recognised in clinical practice, but their prognostic impact is largely uncertain. We hypothesise they modify prognosis as secondary patterns.

      Method

      We retrospectively reviewed the tubulo-papillary-predominant, invasive epithelioid MPM (n=269) as a subset of 614 consecutive epithelioid MPM diagnosed at our institution over a 15-year period. The diagnostic criteria for WDPM-like and cribriform patterns were inferred from those of canonical WDPM and lung adenocarcinoma. Survival analysis was performed using Kaplan-Meier method.

      Result

      We identified 10 cases of tubulo-papillary-predominant epithelioid exhibiting WDPM-like pattern, and one case being predominantly WDPM-like (Estimated incidence 4.1%). They are associated with significantly prolonged median overall survival (78.7 months vs. 18.0 months, p=0.001). On the other hand cribriform neither as predominant (n=9, 3.3%, p=0.672) or secondary growth patterns (n=46, 17.1%, p=0.952) achieved statistical significance in univariate setting compared with tubulo-papillary epithelioid MPM without such pattern.

      wdpm-like.jpg

      cribriform pattern (predominant and secondary).jpg

      Conclusion

      We propose tubulo-papillary-predominant epithelioid MPM with WDPM-like features as a rare and favourable prognostic group. Further molecular analysis is planned. Cribriform pattern does not appear to be prognostically relevant. We recommend external validation of our findings for both growth patterns.

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