P2.04-026 Expression Patterns of PD-L1 in Esophageal Adenocarcinomas: Comparison between Primary Tumors and Metastases: Topic: Esophageal Cancer and Other Malignancies

Abstract

Immune checkpoint inhibition through PD-L1 (Programmed death-ligand 1) is a powerful therapeutic option for many solid tumors, potentially including esophageal adenocarcinomas (EAC). Immunohistochemical expression analysis of PD-L1 may be helpful for guiding therapeutic decisions, but testing may be influenced by heterogeneous staining patterns within tumors and expression changes during metastatic course. We investigated PD-L1 expression in EAC using tissue microarrays from 116 primary resected tumors, corresponding lymph nodes (n=56) and distant metastases (n=18). PD-L1 expression was analyzed using two different antibodies (SP142 and E1LN3), together with intratumoral CD3+ and CD8+ T-lymphocyte (TIL) counts. In addition, preoperative biopsies and full slide sections from a subset of tumors (n=24) were investigated. PD-L1 expression was first scored as 0%, >0-<1%, ≥1%, ≥5%, ≥50% positive membranous staining of tumor cells and of tumor associated inflammatory infiltrates and/or stroma cells. There was a significant correlation between the results of full slide sections and 12 cores/tumor containing TMAs (p=0.001), but not with the corresponding biopsies. For further analysis, PD-L1 positivity was defined as >1% positive staining for tumor cells and/or inflammatory and stroma cells according to the majority of current drug trails. We observed a very good concordance between the two antibodies for overall staining (p<0.001; concordance rate 89.5%). SP142 appeared slightly superior in terms of a more homogenous staining pattern. PD-L1 expression in tumor cells was detected by SP142 in 3 cases (2.6%) of primary EAC, whereas expression in the inflammatory and stromal cells was observed in 35 cases (30.2%). PD-L1 positive tumors had higher CD3+ and CD8+ TIL counts (p<0.001 and p=0.001) but no other distinct pathological or clinical features. Of note, there was no significant correlation between tumoral PD-L1 expression in primary tumors and lymph node and distant metastases. EAC show tumoral PD-L1expression only a minority of cases, whereas PD-L1 positivity in the inflammatory and stromal cells can be detected in a significant subset of cases. For the determination of PD-L1 status, it should be taken into account that PD-L1 expression in metastases may differ from primary tumors. Moreover, investigation of superficial small biopsies may produce false staining results, which, however, may be more likely be due to fixation artifacts or vicinity to ulceration than to intratumoral heterogeneity.