2928 Laboratory parameters have independent prognostic impact in patients with newly diagnosed brain metastases: analysis of 1201 cases

Abstracts to the aggressive transformation of cancer phenotype. EMT has been reported to have an important clinical implication in cancer progression. Pituitary adenomas are brain tumours with invasive properties. These benign tumours, some having endocrine functions by secreting hormones, are able to cause destruction of surrounding tissues. In the present study, we investigated the expression of a panel of EMT markers, namely E-cadherin, N-cadherin, SLUG, SNA1 and TWIST in a cohort of human pituitary adenomas and explored the relationship between the EMT markers and the clinical and pathological feature of the tumour type. Materials and Methods: A cohort of fresh frozen human pituitary tumours (n = 95) was collected immediately after surgery. Histological and immunohistological investigations were carried for histological typing and endocrine function analysis. Gene transcripts of the EMT markers were quantified using quantitive PCR analysis. Levels of expression was analysed against clinical, pathological, invasion and endocrine functions. Results: There was a significant link between SLUG/TWSIT and the destruction of the sella fosa bones (p < 0.030). Levels of E-cadherin and N-cadherin had a respective negative and positive correlation with the appearance of intratumoral cystic lesions of pituitary tumours. E-cadherin and TWIST are also associated with tumour size and tumour staging. EMT markers also showed links with the endocrine functions of pituitary tumours. In pituitary tumours, SLUG and SNA1 had significant correlation with N-cadherin. It was also interesting to note a highly significant correlations between SLUG and SNA1 with mTORC1 (R = 0.54, p < 0.0001 for SLUG and R = 0.07, p < 0.00001). Conclusion: EMT markers are significant indicators of the appearance of cystic lesions, tumour progression, bone destruction and endocrine functions. These markers are valuable biomarkers in assessing the clinical course of pituitary adenomas. No conflict of interest. 2926 POSTER Tumor-infiltrating lymphocytes (TILs) and PDL1 expression in lung cancer brain metastases A.S. Berghoff1 , I. Cansu1 , O. Rajky1 , G. Ricken2 , G. Widhalm3 , K. Dieckmann4 , P. Birner5 , F. Oberndorfer5 , B. Dome6 , R. Bartsch1 , C. Zielinski1 , M. Preusser1 . 1 Medical University of Vienna, Department of Medicine I, Vienna, Austria; 2 Medical University of Vienna, Institute of Neurology, Vienna, Austria; 3 Medical University of Vienna, Department of Neurosurgery, Vienna, Austria; 4 Medical University of Vienna, Department of Radiotherapy, Vienna, Austria; 5 Medical University of Vienna, Clinical Institute of Pathology, Vienna, Austria; 6 Medical University of Vienna, Department of Surgery, Vienna, Austria Background: Brain metastases (BM) are a frequent and devastating complication occurring in up to 50% of patients with metastatic lung cancer. Immune Checkpoint Inhibitors have shown remarkable response in metastatic non-small cell lung cancer (NSCLC), but data on BM are lacking. We aimed to characterize the inflammatory microenvironment including tumor infiltrating lymphocytes (TIL) and expression of programmed cell death ligand 1 (PD-L1) in lung cancer BM and their matched primary tumors. Methods: We performed immunohistochemistry for CD3 and PDL1 in 97 NSCLC BM, 45 matched NSCLC primary tumor (PT) specimens and 24 SCLC BM specimens. Results: Dense infiltration with CD3+ TILs was observed in 81/97 (83.5%) NSCLC BM, 43/45 (95.6%) NSCLC PT and 12/24 (50.0%) SCLC BM. Strong, membranous PDL1 expression in >5% of tumor cells was observed in 22/97 (22.7%) NSCLC BM, 4/45 (8.9%) NSCLC PT and 10/24 (58.3%) SCLC BM. None of the investigated specimens presented with PDL1 expression in >50% of tumor cells. No correlation of CD3+ TILs density (p = 0.439) or PDL1 expression (p = 0.441) was observed between the NSCLC PT and the matched NSCLC BM. Dense infiltration with CD3+ TILs was significantly more frequently observed in NSCLC BM compared to SCLC BM (p < 0.001). PDL1 expression did not show significant differences between NSCLC BM and SCLC BM (p = 0.059). No significant differences in survival prognosis from diagnosis of BM were observed according to CD3+ TIL density in BM specimens (dense 13 months vs. sparse 8 months; p = 0.140). NSCLC patients with PDL1 expression in >5% of BM tumors cells presented with impaired survival prognosis from diagnosis of BM (8 vs. 15 months: p = 0.037). Conclusions: We found PDL1 expression in approximately 23% of NSCLC BM and 58% of SCLC BM. Dense TIL infiltration was more frequently observed in NSCLC BM. Our data support the notion of an immune active microenvironment in BM and may be relevant for clinical trials with immune checkpoint inhibitors in lung cancer BM. No conflict of interest.

S593 2927 POSTER Programmed death ligand 1 (PD-L1) expression and tumor infiltrating lymphocytes in diffuse and anaplastic gliomas A.S. Berghoff1 , B. Kiesel2 , G. Widhalm2 , O. Rajky1 , G. Ricken3 , 3 A. Wohrer ¨ , K. Dieckmann4 , C.C. Zielinski1 , C. Marosi1 , M. Preusser1 . 1 Medical University of Vienna, Department of Medicine I, Vienna, Austria; 2 Medical University of Vienna, Department of Neurosurgery, Vienna, Austria; 3 Medical University of Vienna, Institute of Neurology, Vienna, Austria; 4 Medical University of Vienna, Department of Radiotherapy, Vienna, Austria Background: We investigated the expression of programmed cell death ligand 1 (PD-L1) and infiltration with tumor infiltrating lymphocytes (TILs) in diffuse low-grade and anaplastic gliomas. Methods: We performed immunohistochemical analysis of CD3-positive TILs and PD-L1 expression in 26 diffuse low-grade gliomas (LGG; WHO grade 2) and 21 anaplastic gliomas (WHO grade 3). Histology encompassed 23/47 (48.9%) astrocytoma, 11/47 (23.4) mixed oligoastrocytomas and 13/47 (27.7%) oligodendroglioma. Results: Infiltration by CD3+ TIL was generally sparse and was found in 13/26 (50%) diffuse LGG and 12/21 (57.1%) anaplastic gliomas. PDL1 expression in >25% of tumor cells was found in 22/25 (88.0%) WHO grade 2 and 18/21 (85.7%) WHO grade 3 tumors. Presence of CD3+ TILs (p = 0.626; Chi Square test) or PDL1 expression (p = 0.819; Chi Square test) did not correlate with tumor grade. Further, Presence of CD3+ TILs (p = 0.687; Chi Square test) or PDL1 expression (p = 0.141; Chi Square test) did not correlate with histology. No correlation between CD3+ TIL showed and PDL1 expression was observed (p = 0.819; Chi Square test). Conclusion: We observed sparse infiltration with CD3+ TILs and tumoral PDL1 expression in the majority of WHO grade 2 and 3 diffuse gliomas. Future studies should investigate the value of immune modulatory therapies in these tumor types. No conflict of interest. 2928 POSTER Laboratory parameters have independent prognostic impact in patients with newly diagnosed brain metastases: analysis of 1201 cases A.S. Berghoff1 , R. Koller1 , G. Widhalm2 , K. Dieckmann3 , C.C. Zielinski1 , P. Birner4 , R. Bartsch1 , M. Preusser1 . 1 Medical University of Vienna, Department of Medicine I, Vienna, Austria; 2 Medical University of Vienna, Department of Neurosurgery, Vienna, Austria; 3 Medical University of Vienna, Department of Radiotherapy, Vienna, Austria; 4 Medical University of Vienna, Department of Pathology, Vienna, Austria Introduction: We investigated the prognostic value of laboratory parameters in a large real life cohort of brain metastasis (BM) patients. Methods: 1201 Patients treated for newly diagnosed BM from extracranial solid cancers (472/1201 (39.3%) lung cancer; 266/1201 (22.1%) breast cancer; 163/1201 (13.6%) melanoma; 121/1201 (10.1%) renal cell carcinoma; 101/1207 (8.4%) colorectal cancer; 78/1201 (6.5%) other primary tumor) were included in the analysis. Clinical characteristics including laboratory parameters at diagnosis of BM and survival times were retrieved by chart review. Laboratory parameters with significant impact on overall survival from diagnosis of BM in univariate analysis were entered in multivariable analysis together with known prognostic factors including primary tumor type, graded prognostic assessment (GPA) class and treatment modality for BM. Results: At univariate survival analysis, hemoglobin level upper limit of normal (ULN), serum creatinine concentration >ULN and serum lactate dehydrogenase level (LDH) >ULN correlated with unfavourable overall survival (p < 0.05, log-rank test). At multivariate analysis, hemoglobin (HR 0.8; p = 0.001), platelet count