Bakker, M.A. (Michael) den

Damhuis, R.A. (Ronald)

Derks, J.L. (Jules L.)

Dingemans, A.-M.C. (A-M C)

Groen, H.J.M. (Henk)

Hermans, B.C.M. (B. C.M.)

Palga-Group, P. (P.)

Roemen, G.M. (G. M.)

Smit, E.F. (E. F.)

Speel, E.J. (Ernst-Jan)

Stallinga, C.M. (C. M.)

Suylen, R-J. (Robert-Jan) van

Thunissen, E. (E.)

van den Broek, E.C. (E. C.)

English

Erasmus University Digital Repository

Conclusions:Our results showed the prognostic role of PD-L1, TGF-b and CD8þ TILsin patients with advanced TETs, and their potential for development of anti-PD-1/PD-L1 therapies.Legal entity responsible for the study: JieWang.Funding:Has not received any funding.Disclosure: All authors have declared no conflicts of interest.1813P Prevalence and prognostic value of PD-L1 expression in molecularsubtypes of metastatic large cell neuroendocrine carcinoma (LCNEC)B.C.M. Hermans1, J.L. Derks1, E. Thunissen2, R.J. van Suylen3, M.A. den Bakker4,H.J.M. Groen5, E.F. Smit6, R.A. Damhuis7, E.C. van den Broek8, P. PALGA-group8,C.M. Stallinga9, G.M. Roemen9, E.J. Speel9, A-M.C. Dingemans11Pulmonary Diseases, Maastricht University Medical Center (MUMC), Maastricht,Netherlands, 2Pathology, VU Medical Centre, Amsterdam, Netherlands, 3Pathology-DNA, Jeroen Bosch Ziekenhuis, Den Bosch, Netherlands, 4Pathology, Erasmus UniversityMedical Center, Rotterdam, Netherlands, 5Pulmonary Disease, University HospitalGroningen (UMCG), Groningen, Netherlands, 6Thoracic Oncology, Netherlands CancerInstitute, Amsterdam, Netherlands, 7Research, Comprehensive Cancer Association,Utrecht, Netherlands, 8PALGA foundation, Houten, Netherlands, 9Pathology, MaastrichtUniversity Medical Center, Maastricht (MUMC), NetherlandsBackground: Pulmonary LCNEC is a rare tumor. Twomutually exclusive subtypes ofLCNEC are recognized, the co-mutated TP53 and RB1 and the STK11/KEAP1 (pre-dominantly RB1 wildtype) group.We investigated PD-L1 expression in a well charac-terized stage IV LCNEC cohort and compared expression in the two subtypes.Methods: Panel-consensus pathology revision was performed along with targeted nextgeneration sequencing (TNGS) for genes TP53, RB1, STK11 and KEAP1 and immuno-histochemical (IHC) analysis of RB1, on pretreatment tumor samples of stage IVLCNEC treated with chemotherapy (Derks et al. CCR 2018). IHC staining for PD-L1(DAKO 28-8) was performed according to standard protocols on the DAKO autos-tainer and evaluated by an experienced screener. Tumors were scored positive if> 1%of tumor cells showed anymembranous staining. Overall survival (OS) was evaluatedby KaplanMeier analysis and differences estimated with Log-Rank test. Cox-regressionanalysis included PD-L1, age and gender.Results: PD-L1 IHC expression data could be generated in 98/147 confirmed LCNECsamples along with RB1 IHC (n¼ 97) of which 77 passed quality control for TNGS.PD-L1 expression was positive in 16/98 cases (16%); n¼ 5 (5%) with>50%, n¼ 11(11%) having>1-50% and n¼ 82 (82%) with1%membranous staining, respec-tively. No significant correlation of PD-L1 expression with molecular subtyping ofLCNECwas identified (Table). PD-L1 expression was correlated with a superior OS,hazard ratio (HR) 0.54 ((95%Confidence interval (CI), 0.31-0.96) P¼ 0.034.Table: 1813P Expression of PD-L1 in LCNEC, correlated tomolecular dataPD-L1 þ PD-L1 - P-valueLCNEC (n¼ 98) 16% 84% -1-5% 7 % - -5-20 4% - ->50 5% - -Rb1 IHC (n¼ 97)RB1 (þ) (n¼ 29) 10% 90% NSRB1 (-) (n¼ 68) 19% 81%Mutation status (n¼ 76)RB1/TP53 mutated (n¼ 33) 15% 85% NSRB1 wildtype (n¼ 43) 16% 84%OS in months (95% CI) 8.9(4.2-13.6)6.6(5.7-7.6)HR 0.54(0.31-0.96) P¼ 0.034Conclusions: PD-L1 expression was positive in 16% of stage IV LCNEC tumors. PD-L1 expression is an independent process from LCNECmolecular subgroups. InLCNEC patients with PD-L1 expression superior OS is observed compared to thosewith negative PD-L1 tumors.Legal entity responsible for the study:Maastricht University Medical Centre,Department of Pulmonary Disease.Funding: Bristol-Meyers Squibb.Disclosure: All authors have declared no conflicts of interest.1814P Computed tomography features of resected lung adenocarcinomaswith spread through air spacesY. Yamada1, G. Toyokawa2, T. Tagawa3, T. Kamitani4, Y. Yamasaki4, F. Shoji2,K. Yamazaki2, S. Takeo2, Y. Oda11Department of Anatomic Pathology, Graduate School of Medical Sciences, KyushuUniversity, Fukuoka, Japan, 2Department of Thoracic Surgery, National HospitalOrganization, Kyushu Medical Center, Fukuoka, Japan, 3Department of Surgery andScience, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan,4Department of Clinical Radiology, Graduate School of Medical Sciences, KyushuUniversity, Fukuoka, JapanBackground: Spread through air spaces (STAS) is a recently-recognized invasive pat-tern of lung cancer defined as ‘micropapillary clusters, solid nests or single cells beyondthe edge of the tumor into air spaces.’ Since STAS has been shown to be a significantprognosticator for the postoperative survival, predicting STAS preoperatively by com-puted tomography (CT)might help determine the optimum surgical procedures.Methods: Information on STAS and preoperative CT were availablen 327 patients withresected lung adenocarcinomas. STAS was defined as tumor cells within air spaces inthe lung parenchyma beyond the edge of the main tumor. The association of STAS withCT characteristics, such as vascular convergence, ground glass opacity (GGO), airbronchogram, notch, pleural indentation, spiculation, and cavitation, was analyzed.Results: Among the 327 patients with resected adenocarcinoma, 191 (58.4%) were pos-itive for STAS. A univariable analysis demonstrated that STAS-positive adenocarcino-mas were significantly associated with a larger radiological tumor diameter (P¼ 0.02),the presence of vascular convergence (P< 0.01), notch (P< 0.01), pleural indentation(P¼ 0.03), spiculation (P< 0.01), and the absence of GGO (P< 0.01) compared withSTAS-negative ones. In amultivariable analysis, the presence of notch (P¼ 0.01) andthe absence of GGO (P< 0.01) were shown to be significantly associated with the STASphenomenon. The odds ratio for STAS of notch-positive and GGO-negative adenocar-cinomas against notch-negative and GGO-positive ones was 5.01 (P< 0.01).Conclusions: The presence of notch and the absence of GGOwere independently asso-ciated with the STAS phenomenon. These results will prove helpful in identifyingSTAS-positive adenocarcinoma by CT prior to surgical resection.Legal entity responsible for the study:Gouji Toyokawa.Funding:Has not received any funding.Disclosure: All authors have declared no conflicts of interest.1815P Comparative proteomic analysis of acetylation profiles in esophagealsquamous carcinoma cellsY. Dai1, J. Li21Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian MedicalUniversity, Fuzhou, China, 2Radiation Oncology, Fujian Cancer Hospital, Fuzhou, ChinaBackground: To explore the different expression of proteins and the acetylationsbetween esophageal squamous carcinoma cells (ESCCs) and cancer stem-like cells(CSCs) by proteomic analysis.Methods: The Eca109 cells were divided into CSCs group and ESCCs group by usingserum-free culture and serum culture. Wemeasured the CD44 expression levels, CCK8cell proliferations and plate cloning formation to identify the characteristics of cancerstem cells. Furthermore, TandemMass Tags (TMT)-based quantitative proteomicsand bioinformatic analysis were used to detect proteomics and bioinformatic analysis.Results: The positive rate of CD44 and CCK8 cell proliferation experience in the CSCsgroup were higher than ESCCs group (P< 0.05). The plate cloning formation showedthat the values of D0, Dq, N and SF2 were significantly higher in the CSCs group, andthe radiation sensitization ratio was 1.556. Furthermore, 5,262 proteins were identifiedin the two groups in total. The up-regulation of 187 proteins and down-regulation of83 proteins were detected in CSCs group (>1.5 times). Bioinformatic analysis furtherrevealed that those quantifiable proteins were mainly involved in multiple biologicalfunctions and metabolic processes, including steroid biosynthesis, protein processingin endoplasmic reticulum, metabolic pathways and oxidative phosphorylation path-ways. In addition, 53 acetylated sites were increased and 67 acetylated sites weredecreased in CSCs group (>1.5 times). Those acetylated sites were involved in the regu-lation of DNAmetabolic process, the function of cell adhesion, glycolysis and gluco-neogenic pathway.Conclusions:We provides a global survey of proteins and acetylations in ESCCs andCSCs. These proteins and acetylations may be related to the radiosensitivity, recurrenceandmetastatic of esophageal squamous carcinoma and could be a potential new targetfor esophageal squamous carcinoma.Legal entity responsible for the study: Jiancheng Li.Funding:Has not received any funding.Disclosure: All authors have declared no conflicts of interest.Annals of Oncology abstractsVolume 29 | Supplement 8 | October 2018 doi:10.1093/annonc/mdy301 | viii643This is an Open Access article under the  CC-BY-NC license.-ND

Prevalence and prognostic value of PD-L1 expression in molecular subtypes of metastatic large cell neuroendocrine carcinoma (LCNEC)

https://repub.eur.nl/pub/125535/Repub_125535_O-A.pdf

Prevalence and prognostic value of PD-L1 expression in molecular subtypes of metastatic large cell neuroendocrine carcinoma (LCNEC)

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