Expression patterns of programmed death-ligand 1 in esophageal adenocarcinomas: comparison between primary tumors and metastases

Abstract

Expression analysis of programmed death-ligand 1 (PD-L1) may be helpful in guiding clinical decisions for immune checkpoint inhibition therapy, but testing by immunohistochemistry may be hampered by heterogeneous staining patterns within tumors and expression changes during metastatic course. PD-L1 expression (clone SP142) was investigated in esophageal adenocarcinomas using tissue microarrays (TMA) from 112 primary resected tumors, preoperative biopsies and full slide sections from a subset of these cases (n = 24), corresponding lymph node (n = 55) and distant metastases (n = 17). PD-L1 expression was scored as 0.1-1, >1, >5, >50% positive membranous staining of tumor cells and any positive staining of tumor-associated inflammatory infiltrates and/or stroma cells. There was a significant correlation with overall PD-L1 expression between the full slide sections and the TMA (p = 0.001), but not with the corresponding biopsies. PD-L1 expression in tumor cells >1% was detected in 8.0% of cases (9/112) and 51.8% of cases (58/112) in tumor-associated inflammatory infiltrates and/or stroma cells of primary tumors. Epithelial expression in metastases was found in 5.6% of cases (4/72) and immune cell expression in 18.1% of cases (13/72), but did not correlate with the expression pattern in the primary tumor. Overall PD-L1 expression in the primary tumor did not influence survival. However, PD-L1 expression was correlated with the number of CD3 tumor-infiltrating lymphocytes in the tumor center, and a combinational score of PD-L1 status/CD3 tumor-infiltrating lymphocytes was correlated with patients' overall survival.

PD-L1 and PD-1 and characterization of tumor-infiltrating lymphocytes in high grade sarcomas of soft tissue – prognostic implications and rationale for immunotherapy

“…In addition, previous studies were able to confirm staining results based on TMA on whole slides. 45 In our study, scoring based on TMAs was concordant with scoring of whole slide sections in selected cases, making any bias unlikely.…”

Adverse prognostic value of PD-L1 expression in primary resected pulmonary squamous cell carcinomas and paired mediastinal lymph node metastases

“…PD-L1 immunohistochemistry was performed using laboratory-developed tests using clone SP142 (Spring Bioscience, Pleasanton, CA, USA) and clone E1L3N (Cell Signaling Technology, Danvers, MA, USA) at a dilution of 1:400 each, as described before. 21 Both PD-L1 clones have been validated for specificity. [21][22][23] Deparaffinized sections were rehydrated in Dewax dilution (Leica Biosystems) for 20 min, and antigen retrieval was performed with Tris-HCl, pH 9 for 40 min at 95°C.…”

“…21 Both PD-L1 clones have been validated for specificity. [21][22][23] Deparaffinized sections were rehydrated in Dewax dilution (Leica Biosystems) for 20 min, and antigen retrieval was performed with Tris-HCl, pH 9 for 40 min at 95°C. Endogenous peroxidase activity was blocked with H 2 O 2 solution (Leica Biosystems).…”

The Determination of Immunomodulation and Its Impact on Survival of Rectal Cancer Patients Depends on the Area Comprising a Tissue Microarray

“…The impact of the tumor immune contexture on the prognosis of CRC patients is not doubted and the consensus Immunoscore is internationally validated for implementation of a "TNM-Immune classification" of cancer [31]. However, concerns have been raised regarding the methodology used for immune marker quantification using TMA in particular [20][21][22][23][24][25]32].…”

“…Recently, several issues have been raised concerning the method of immune marker quantification employed. Spatial tumor heterogeneity of target molecules in cancer tissue is well described [20][21][22][23][24][25][26]; however, histologic sampling by TMA is still regularly used for marker analysis [18,27,28], although it involves the risk of underestimation [22,24,28]. The Immunoscore uses two cores in two tumor areas each (CT, IM) for quantification of immune cell densities in CRC [18,27].…”