Conclusions: Our results showed the prognostic role of PD-L1, TGF-b and CD8þTILs in patients with advanced TETs, and their potential for development of anti-PD-1/PD-L1 therapies.
Legal entity responsible for the study: Jie Wang. 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 molecular subtypes 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. Dingemans1 1
Pulmonary Diseases, Maastricht University Medical Center (MUMC), Maastricht, Netherlands,2
Pathology, VU Medical Centre, Amsterdam, Netherlands,3 Pathology-DNA, Jeroen Bosch Ziekenhuis, Den Bosch, Netherlands,4
Pathology, Erasmus University Medical Center, Rotterdam, Netherlands,5
Pulmonary Disease, University Hospital Groningen (UMCG), Groningen, Netherlands,6
Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands,7
Research, Comprehensive Cancer Association, Utrecht, Netherlands,8
PALGA foundation, Houten, Netherlands,9
Pathology, Maastricht University Medical Center, Maastricht (MUMC), Netherlands
Background:Pulmonary LCNEC is a rare tumor. Two mutually exclusive subtypes of LCNEC 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 next generation sequencing (TNGS) for genes TP53, RB1, STK11 and KEAP1 and immuno-histochemical (IHC) analysis of RB1, on pretreatment tumor samples of stage IV LCNEC 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 any membranous staining. Overall survival (OS) was evaluated by Kaplan Meier analysis and differences estimated with Log-Rank test. Cox-regression analysis included PD-L1, age and gender.
Results:PD-L1 IHC expression data could be generated in 98/147 confirmed LCNEC samples 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%, n ¼ 11 (11%) having >1-50% and n¼ 82 (82%) with 1% membranous staining, respec-tively. No significant correlation of PD-L1 expression with molecular subtyping of LCNEC was 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 to molecular data PD-L1þ PD-L1 - P-value LCNEC (n¼ 98) 16% 84% -1-5% 7 % - -5-20 4% - ->50 5% - -Rb1 IHC (n¼ 97) RB1 (þ) (n ¼ 29) 10% 90% NS RB1 (-) (n¼ 68) 19% 81% Mutation status (n¼ 76) RB1/TP53 mutated (n¼ 33) 15% 85% NS RB1 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 0.034
Conclusions:L1 expression was positive in 16% of stage IV LCNEC tumors. PD-L1 expression is an independent process from LCNEC molecular subgroups. In LCNEC patients with PD-L1 expression superior OS is observed compared to those with 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 adenocarcinomas with spread through air spaces
Y. Yamada1 , G. Toyokawa2 , T. Tagawa3 , T. Kamitani4 , Y. Yamasaki4 , F. Shoji2 , K. Yamazaki2 , S. Takeo2 , Y. Oda1 1
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan,2
Department of Thoracic Surgery, National Hospital Organization, Kyushu Medical Center, Fukuoka, Japan,3
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, 4
Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Background: Spread through air spaces (STAS) is a recently-recognized invasive pat-tern of lung cancer defined as ‘micropapillary clusters, solid nests or single cells beyond the edge of the tumor into air spaces.’ Since STAS has been shown to be a significant prognosticator 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 with resected lung adenocarcinomas. STAS was defined as tumor cells within air spaces in the lung parenchyma beyond the edge of the main tumor. The association of STAS with CT characteristics, such as vascular convergence, ground glass opacity (GGO), air bronchogram, 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-pospos-itive 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 with STAS-negative ones. In a multivariable analysis, the presence of notch (P¼ 0.01) and the absence of GGO (P < 0.01) were shown to be significantly associated with the STAS phenomenon. 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 GGO were independently asso-ciated with the STAS phenomenon. These results will prove helpful in identifying STAS-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 esophageal squamous carcinoma cells
Y. Dai1 , J. Li2 1
Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Medical University, Fuzhou, China,2
Radiation Oncology, Fujian Cancer Hospital, Fuzhou, China Background: To explore the different expression of proteins and the acetylations between 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 using serum-free culture and serum culture. We measured the CD44 expression levels, CCK8 cell proliferations and plate cloning formation to identify the characteristics of cancer stem cells. Furthermore, Tandem Mass Tags (TMT)-based quantitative proteomics and bioinformatic analysis were used to detect proteomics and bioinformatic analysis. Results: The positive rate of CD44 and CCK8 cell proliferation experience in the CSCs group were higher than ESCCs group (P < 0.05). The plate cloning formation showed that the values of D0, Dq, N and SF2 were significantly higher in the CSCs group, and the radiation sensitization ratio was 1.556. Furthermore, 5,262 proteins were identified in the two groups in total. The up-regulation of 187 proteins and down-regulation of 83 proteins were detected in CSCs group (>1.5 times). Bioinformatic analysis further revealed that those quantifiable proteins were mainly involved in multiple biological functions and metabolic processes, including steroid biosynthesis, protein processing in endoplasmic reticulum, metabolic pathways and oxidative phosphorylation path-ways. In addition, 53 acetylated sites were increased and 67 acetylated sites were decreased in CSCs group (>1.5 times). Those acetylated sites were involved in the regu-lation of DNA metabolic process, the function of cell adhesion, glycolysis and gluco-neogenic pathway.
Conclusions: We provides a global survey of proteins and acetylations in ESCCs and CSCs. These proteins and acetylations may be related to the radiosensitivity, recurrence and metastatic of esophageal squamous carcinoma and could be a potential new target for 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.
