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M. Goldoni
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P3.03 - Poster Session with Presenters Present (ID 473)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.03-012 - Tumor-Infiltrating Lymphocytes, PDL-1, BAP-1, VEGFR-2 and IGF-1R Expression in Malignant Pleural Mesothelioma (ID 4142)
14:30 - 14:30 | Author(s): M. Goldoni
- Abstract
Background:
to investigate whether there was any relationship between survival and the expression of tumor infiltrating lymphocytes (TILs), programmed cell-death-ligand-1 (PDL-1), BAP-1 (BRCA1-Associated Protein 1), VEGFR-2 (vascular endothelial growth factor receptor 2) and IGF-1R (Insulin-Like Growth Factor 1 Receptor) in malignant pleural mesothelioma (MPM).
Methods:
63 cases of MPM were identified. All tissues were obtained at the time of diagnosis. There were 40 males; mean age was 70.4 years. 34 patients were smokers and 40 had a certain history of asbestos exposure. All histological slides were revised; there were 30 epithelioid subtypes, 20 biphasics and 13 sarcomatoids. The presence of TILs was scored as absent, weak, moderate and strong according to a quantitative assessment on hematoxylin and eosin slides. The expression of BAP-1, VEGFR-2, PDL-1 and IGF-1R was analyzed by immunohistochemistry. The impact of asbestos exposure, tobacco consumption and histological subtypes on survival were also assessed. The survival analysis was analyzed by Kaplan Meier curve.
Results:
TILs were present in 89% of cases and were found to be a favorable prognostic factor (p=0.009) although related with histological subtypes (p=0.008). The absence of TILs was higher in biphasic and sarcomatoid subtypes (90.9%, 30/33) compared to epithelioid MPM (53.3%, 16/30 p<0.001). Median survival in TILs and non-TILs patients was 28 months and 11 months, respectively. The expression of PDL-1 in tumor cells (cut-off: 10%, p=0.028) and VEGFR-2 in TILs (p=0.003) were related with survival, but they were differently expressed in histological subtypes. Using a logistic regression model, TILs, PDL-1 and VEGFR-2 in TILs correctly classified 21/30 epithelioid subtypes (70%) and 29/33 biphasic and sarcomatoid subtypes (87.9%). IGF-1R was overexpressed in 82% of the tumors (21 epitheliods and 31 sarcomatoids) and in 25% of TILs (7 epitheliods and 3 sarcomatoids) and was a favorable prognostic factor (p=0.023) independently of the histological subtype. Median survival was 4 and 13 months in patients not overexpressing and overexpressing IGF-1R, respectively. In a Cox regression model including both IGF-1R and histological subtype, IGF-1R remained significant [p=0.006, HR=0.41 (0.20-0.84)]. Tobacco, asbestos exposure, age and BAP-1 expression were not significantly related with survival.
Conclusion:
the histological subtype is an important prognostic factor in MPM and it’s related to different histological markers: the presence of TILs, PDL-1 and VEGFR-2 in TILs. Moreover, the overexpression of IGF-1R is an independent favorable prognostic factor. Therefore, histological markers may improve the prognostic assessment of MPM and provide mechanistic clues for new therapeutic strategies.
