P3.03-012 Tumor-Infiltrating Lymphocytes, PDL-1, BAP-1, VEGFR-2 and IGF-1R Expression in Malignant Pleural Mesothelioma: Topic: Mesothelioma Transitional

Abstract

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). 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. 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. 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.