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Review
. 2023 Apr;115(2):57-70.
doi: 10.32074/1591-951X-836. Epub 2022 Dec 19.

A practical approach for PD-L1 evaluation in gastroesophageal cancer

Valentina Angerilli #  1 , Matteo Fassan #  1   2 , Paola Parente  3 , Irene Gullo  4   5   6 , Michela Campora  7 , Chiara Rossi  8 , Maria Luisa Sacramento  4 , Gianmaria Pennelli  1 , Alessandro Vanoli  8 , Federica Grillo #  9   10 , Luca Mastracci #  9   10
Affiliations
Review

A practical approach for PD-L1 evaluation in gastroesophageal cancer

Valentina Angerilli et al. Pathologica. 2023 Apr.

Abstract

PD-L1 is an established predictive immunohistochemical biomarker of response to immune checkpoint inhibitors. At present, PD-L1 is routinely assessed on biopsy samples of advanced gastroesophageal cancer patients before initiating first-line treatment. However, PD-L1 is still a suboptimal biomarker, due to changing cut-off values and scoring systems, interobserver and interlaboratory variability.

This practical illustrated review discusses the range of staining patterns of PD-L1 and the potential pitfalls and challenges that can be encountered when evaluating PD-L1, focusing on gastric and gastroesophageal adenocarcinoma (G/GEA) and esophageal squamous cell carcinoma (ESCC).

Keywords: PD-L1; esophageal squamous cell carcinoma; gastroesophageal adenocarcinoma; immunohistochemistry; immunotherapy.

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Conflict of interest statement

The authors declare no conflict of interest related to the present work.

Figures

Figure 1.
Figure 1.
Linear membrane and cytoplasmic staining.
Figure 2.
Figure 2.
Complete and incomplete membrane staining.
Figure 3.
Figure 3.
Intense, moderate and weak membrane staining.
Figure 4.
Figure 4.
Positive lymphocytes.
Figure 5.
Figure 5.
Positive macrophages.
Figure 6.
Figure 6.
Positive plasma cells.
Figure 7.
Figure 7.
Small tumor area with PD-L1 Staining.
Figure 8.
Figure 8.
Heterogenous PD-L1 staining.
Figure 9.
Figure 9.
PD-L1 staining and morphologic heterogeneity.
Figure 10.
Figure 10.
PD-L1 positivity in pre-invasive lesions.
Figure 11.
Figure 11.
PD-L1 positivity in an ulcerated area.
Figure 12.
Figure 12.
Non-specific staining.
Figure 13.
Figure 13.
DAB staining.
Figure 14.
Figure 14.
Edge effect.
Figure 15.
Figure 15.
Electrocution artifacts.
Figure 16.
Figure 16.
Poor fixation artifacts.
Figure 17.
Figure 17.
Biopsy specimen with less than 100 cells, from a patient with marked thickening of the stomach walls. Out of a total of 6 biopsies submitted (2 are shown here) only one had a small focus of neoplastic cells. The only area with diagnostic tumor cells is seen in the oval in A and this is shown at higher magnification in the oval in B, where approximately 50 neoplastic cells are seen in total.
Figure 18.
Figure 18.
PD-L1 staining in post-neoadjuvant therapy specimen.
Figure 19.
Figure 19.
Same tissue specimen showing different staining patterns of Ventana SP142 and Dako 22C3.
Figure 20.
Figure 20.
Mucinous adenocarcinoma.
Figure 21.
Figure 21.
Signet ring cell carcinoma.
Figure 22.
Figure 22.
Carcinoma with lymphoid stroma.
Figure 23.
Figure 23.
Hepatoid carcinoma.
Figure 24.
Figure 24.
Mismatch repair deficient (MMRd)/microsatellite instable (MSI) gastric adenocarcinoma with high PD-L1 expression.
None
See this image and copyright information in PMC

References

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