Prognostic Value of PD-L1 Immunohistochemical Marker in Gastric Carcinoma and Its Correlation with HER2 Status

Attia, Samar; hafez, Amal Abd El; Abdel-Aziz, Azza; Elmetwaly, Shimaa; Mokhtar, Nagwa

doi:10.31557/apjcp.2022.23.4.1433

Cited by 9 publications

(5 citation statements)

References 37 publications

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“…HER2 has been documented to be amplified and overexpressed in a variety of human cancers, which is correlated with a worse prognosis, higher recurrence rates and shorter OS ( 27 ). A number of studies established that HER2 controls the abnormal expression of PD-L1 in the stomach and the combination of anti-HER2 and anti-PD-1 has proven synergistic anticancer effects in animal models ( 16 , 28 , 29 ). Further studies disclosed that dimerization of the HER2 receptor activates two major intracellular signaling pathways: the mitogen-activated protein kinase (MAPK) (Ras/Raf/MEK/ERK) and phosphatidylinositol 3′-kinase (PI3K)/Akt, inducing cell-cycle progression, proliferation and survival ( 30 – 32 ).…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of PD‑L1 expression and CD68 macrophages in tumor nest of patients with primary gastric cancer

Zou,

Wang,

Zhang

et al. 2023

Oncol Lett

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The programmed death receptor 1/programmed death receptor ligand 1 axis (PD-1/PD-L1) is involved in tumor immune escape and is a potential prognostic biomarker and anti-tumor immunotherapy target in patients with gastric cancer (GC). However, the results of studies obtained in recent years have been inconsistent. The present study aimed to determine the possible predictive significance of PD-L1 in conjunction with three proteins linked with PD-L1 regulation in patients with primary GC. In the present study, the PD-L1, human epidermal growth factor receptor 2 (HER2), cluster of differentiation (CD)133 and microphage-associated CD68 expression levels were identified by multiplexed immunohistochemistry and assessed by automated pathological analysis system in 93 GC tumors and neighboring normal tissues arrayed on the same tissue microarray. All four proteins were statistically analyzed in relation to the clinicopathological characteristics. The expression levels of HER2, CD133 and CD68 were considerably higher in cancer tissues compared with neighboring normal tissues (P<0.05), however, the reverse trend was detected for PD-L1 expression (P=0.0577), particularly in tumor nest (TN; P<0.05). There was no significant correlation between the HER2 and CD133 expression levels and clinicopathological factors. However, significant relationships were found between PD-L1 expression and the TNM stage, pathological differentiation and survival status of patients (P<0.05). Moreover, survival time was prolonged in individuals with elevated PD-L1 expression in TN and GC tissues, but no significant correlation was identified (P=0.0881). The CD68 expression level in tumor stroma, but not in TN, was significantly correlated with poor pathological differentiation in patients with GC (P<0.05). However, PD-L1+CD68+ macrophages were strongly related to lower tumor size (diameter <5 cm), early TNM stage (stage I+II), good pathological differentiation and overall survival in TN (P<0.05). In conclusion, PD-L1+CD68+ macrophage infiltration in TN might be a potential indicator of prognosis in patients with primary GC and merits further investigation.

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Section: Discussionmentioning

confidence: 99%

Prognostic value of PD‑L1 expression and CD68 macrophages in tumor nest of patients with primary gastric cancer

Zou,

Wang,

Zhang

et al. 2023

Oncol Lett

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“…Two previous meta-analyses have suggested that HER2 expression is associated with male sex, differentiated tumors, intestinal type, and lymph node metastasis [ 21 22 ]. The correlation between HER2 and PD-L1 expression is unclear, given the inconsistent results reported in previous studies [ 23 24 25 26 ]. The presence of MSI-high was less frequent in HER2-positive tumors than that in HER2-negative tumors [ 27 28 ].…”

Section: Her2: Beyond Trastuzumabmentioning

confidence: 97%

Emerging Targets for Systemic Treatment of Gastric Cancer: HER2 and Beyond

Kim

2024

J Gastric Cancer

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In recent years, remarkable progress has been made in the molecular profiling of gastric cancer. This progress has led to the development of various molecular classifications to uncover subtype-specific dependencies that can be targeted for therapeutic interventions. Human epidermal growth factor receptor 2 (HER2) is a crucial biomarker for advanced gastric cancer. The recent promising results of novel approaches, including combination therapies or newer potent agents such as antibody-drug conjugates, have once again brought attention to anti-HER2 targeted treatments. In HER2-negative diseases, the combination of cytotoxic chemotherapy and programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors has become the established standard of care in first-line settings. In the context of gastric cancer, potential biomarkers such as PD-L1 expression, Epstein-Barr virus, microsatellite instability, and tumor mutational burden are being considered for immunotherapy. Recently, promising results have been reported in studies on anti-Claudin18.2 and fibroblast growth factor receptor 2 treatments. Currently, many ongoing trials are aimed at identifying potential targets using novel approaches. Further investigations will be conducted to enhance the progress of these therapies, addressing challenges such as primary and acquired resistance, tumor heterogeneity, and clonal evolution. We believe that these efforts will improve patient prognoses. Herein, we discuss the current evidence of potential targets for systemic treatment, clinical considerations, and future perspectives.

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“…In gastric cancer, PD-L1 CPS ≥ 1 generally defines PD-L1-positive tumors [62]. Some studies have reported significantly higher PD-L1 expression rates in HER2negative tumors [24,63], while other studies reported opposite findings [64,65] or found no differences in PD-L1 expression between HER2-positive and negative tumors [7,66]. These discrepancies may be due to the heterogeneity of the populations studied, differences in the scoring methods, or in the monoclonal antibodies used for detection.…”

Section: Pd-l1 Expression In Her2-positive Gastric Cancermentioning

confidence: 99%

HER2-Positive Gastric Cancer: The Role of Immunotherapy and Novel Therapeutic Strategies

Pous

Notario

Hierro

et al. 2023

IJMS

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Gastric cancer is an aggressive disease with increasing global incidence in recent years. Human epidermal growth receptor 2 (HER2) is overexpressed in approximately 10–20% of gastric cancers. The implementation of targeted therapy against HER2 as part of the standard of care treatment in metastatic disease has improved the prognosis of this subset of patients. However, gastric cancer still has high mortality rates and urgently requires new treatment strategies. The combination of immunotherapy with HER2-targeted therapies has shown synergistic effects in preclinical models, this being the rationale behind exploring this combination in clinical trials in locally advanced and metastatic settings. Additionally, the irruption of antibody–drug conjugates and other novel HER2-targeted agents has led to the development of numerous clinical trials showing promising results. This review presents the molecular mechanisms supporting the use of HER2-targeted drugs in combination with immunotherapy and provides an overview of the therapeutic scenario of HER2-positive disease. We focus on the role of immunotherapy but also summarize emerging therapies and combinations under clinical research that may change the standard treatment in HER-2 positive disease in the future.

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Prognostic Value of PD-L1 Immunohistochemical Marker in Gastric Carcinoma and Its Correlation with HER2 Status

Cited by 9 publications

References 37 publications

Prognostic value of PD‑L1 expression and CD68 macrophages in tumor nest of patients with primary gastric cancer

Prognostic value of PD‑L1 expression and CD68 macrophages in tumor nest of patients with primary gastric cancer

Emerging Targets for Systemic Treatment of Gastric Cancer: HER2 and Beyond

HER2-Positive Gastric Cancer: The Role of Immunotherapy and Novel Therapeutic Strategies

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