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. 2020 Oct;26(4):2225-2235.
doi: 10.1007/s12253-020-00814-2. Epub 2020 May 5.

PD-L1 and HER2 Expression in Gastroesophageal Cancer: a Matched Case Control Study

Andrea Beer  1   2 , Hossein Taghizadeh  2   3 , Ana-Iris Schiefer  1   2 , Hannah C Puhr  2   3 , Alexander K Karner  2   3 , Gerd Jomrich  2   4 , Sebastian F Schoppmann  2   4 , Renate Kain  1   2 , Matthias Preusser  2   3 , Aysegül Ilhan-Mutlu  5   6
Affiliations

PD-L1 and HER2 Expression in Gastroesophageal Cancer: a Matched Case Control Study

Andrea Beer et al. Pathol Oncol Res. 2020 Oct.

Abstract

Immunotherapy with check-point inhibitors serves as a promising treatment strategy in patients with upper gastrointestinal (GI) tumors. Human epidermal growth factor receptor 2 (HER2) is the only identified therapeutic target in upper GI tumors, whose potential interaction with programmed death-ligand 1 (PD-L1) is unknown. The aim of this study was the investigation of PD-L1 and HER2 in upper GI tumors. We retrospectively identified patients with HER2 positive gastroesophageal cancers and matched them with a HER2 negative group. We investigated the tumor specimens for HER2 status and PD-L1 expression, with the following assessments being performed: i) staining of tumor cells in terms of tumor proportion score (TPS), ii) staining for tumor-associated immune cells (TAIs), iii) interface pattern and iv) combined positive score (CPS). Both HER2 positive and negative group consisted of 59 patients. Expression of PD-L1 in TAIs and interface pattern were associated with a favorable outcome (p = 0.02, HR = 0.8; p = 0.04, HR = 0.39; respectively) in patients with localized disease, whereas TPS was associated with an unfavorable outcome in patients with advanced tumor (p = 0.02, HR = 1.4). These effects were HER2 independent. PD-L1 expression in its different assessment is equally observed in HER2 positive and negative patients. Future studies will show whether dual inhibition of HER2 and PD-L1 improves survival of this selected patient population.

Keywords: CPS; Esophageal tumor; Gastric tumor; Gastroesophageal junction tumor; Gastroesophageal tumor; HER2; Immunotherapy; PD-L1; TPS.

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Conflict of interest statement

HC.P. has received travel support from Eli Lilly, MSD, Novartis, Pfizer and Roche.

M.P. has received honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Merck Sharp & Dome.

A.I-M. participated in advisory boards from MSD and Servier, received lecture honoraria from Eli Lilly and Servier, is the local PI for clinical trials sponsored by BMS and Astellas.

Other authors have nothing to declare.

Figures

Fig. 1
Fig. 1
PD-L1 expression levels using different assessments n, number; HER2, human epidermal growth factor receptor 2; TPS, tumor proportion score; TAI, tumor associated immune cells; CPS, combined positive score. Positivity of each assessment (except interface pattern) are demonstrated in continuous variables within X-axis
Fig. 2
Fig. 2
a and b: Membranous expression (and rarely cytoplasmic staining not used for scoring) of PD-L1 in tumor cells (magnification 200x) c: PD-L1 expression of tumor associated immune cells (magnification 200x) d: Example of interface pattern. PD-L1-positive immune cells at the interface between carcinoma (top left) and adjacent stroma (magnification 100x)
See this image and copyright information in PMC

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