Clinicopathological Features and Prognostic Implication of Gastric Carcinoma with Lymphoid Stroma

Pyo, Jung‐Soo; Kim, Nae Yu; Son, Byoung Kwan; Lee, Hyoyoung; Oh, Il Hwan; Chung, Kwang Hyun

doi:10.1155/2020/6628412

Cited by 8 publications

(7 citation statements)

References 43 publications

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“…From a morphological point of view, PD-L1 is more frequently expressed in intestinal and mixed type gastric adenocarcinomas (54% and 56%, respectively), as compared to diffuse gastric cancer (32%) 39 . Within the rare histopathological variants recognized by the WHO classification, gastric carcinoma with lymphoid stroma (also known as medullary carcinoma or lymphoepithelioma-like carcinoma) is of particular interest when considering morphological biomarkers for targeted immunotherapies: the majority of gastric carcinomas with lymphoid stroma show expression of PD-L1 in tumor (33-68%) and/or immune (77-92%) cells 40 , 41 .…”

Section: Pd-l1 In Gastroesophageal Cancersmentioning

confidence: 99%

“…The morphological features of gastric carcinoma with lymphoid stroma are also relevant to identifying these specific molecular subtypes, as EBV infection and MSI status are identified in up to 80% of cases 40 , 41 , 47 . Based on these findings, some authors have suggested systematically performing EBER in situ hybridization and immunohistochemistry for mismatch repair proteins in gastric cancers presenting the morphologic features of gastric cancer with lymphoid stroma, for a cost-effective molecular characterization and selection of patients for targeted immunotherapies 40 , 48 .…”

Section: Pd-l1 In Gastroesophageal Cancersmentioning

confidence: 99%

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PD-L1 evaluation in the gastrointestinal tract: from biological rationale to its clinical application

et al. 2022

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Summary Immune-checkpoint inhibitors targeting the PD-1/PD-L1 axis have brought significant clinical benefit in many solid cancer types, including gastrointestinal malignancies. However, it has been estimated that only 20-40% of patients respond to treatment. The pattern of expression and potential predictive value of PD-L1 as an immunohistochemical biomarker has been extensively studied in gastrointestinal neoplasms. Until now, its predictive value has been demonstrated, and is currently in use only in upper gastrointestinal malignancies (gastroesophageal adenocarcinoma and esophageal squamous cell carcinoma). In this Review, we describe the technical aspects and challenges related to PD-L1 immunohistochemical assays, the current role of PD-L1 as a biomarker in clinical practice and we outline the main studies and clinical trials analyzing the prognostic and predictive value of PD-L1 in gastrointestinal cancers.

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Section: Pd-l1 In Gastroesophageal Cancersmentioning

confidence: 99%

Section: Pd-l1 In Gastroesophageal Cancersmentioning

confidence: 99%

PD-L1 evaluation in the gastrointestinal tract: from biological rationale to its clinical application

et al. 2022

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“… 3 , 4 Histologically, EBVaGC is particularly enriched in lymphoepithelioma-like carcinoma (LELC) (75.7% to 90.3%), 5 also known as GC with lymphoid stroma or medullary carcinoma. 6 , 7 Based on the pattern of host inflammatory immune responses, EBVaGCs can be further classified into three histological subtypes, including LELC, adenocarcinoma with Crohn’s disease-like lymphocytic reaction (CLR), and conventional adenocarcinoma (CA). 3 Molecularly, EBVaGC is characterized by hypermethylation of tumor suppressor genes, mutations in PIK3CA and recurrent amplification at 9p24.1, a chromosomal region harboring CD274 , JAK2 and PDCD1LG2 genes.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Perspectives of STING and PD-L1 Expression and Correlation with the Prognosis of Epstein-Barr Virus-Associated Gastric Cancers

Sun

Chen

et al. 2022

Gut and Liver

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Background/Aims Epstein-Barr virus-associated gastric cancers (EBVaGCs) have unique molecular and clinicopathological characteristics. The cyclic GMP-AMP synthase-stimulator of interferon genes (STING) pathway is recently recognized as the critical innate immunity against pathogens and tumors. STING is also a master regulator in the cancer-immunity cycle and targeting STING could synergize with existing immune-checkpoint therapies. However, the role of STING in GC, especially in EBVaGC, and its correlation with programmed death-ligand 1 (PD-L1) remain largely unclear. Methods We collected 78 cases of EBVaGCs and 210 cases of EBV-negative GC (EBVnGC) from a total of 1,443 cases of GC analyzed by EBV-encoded small RNA in situ hybridization. We investigated STING and PD-L1 expression and their concomitant prognostic value in EBVaGCs and EBVnGCs using tissue microarray and immunohistochemistry. The effects of STING and PD-L1 expression on the overall survival of patients with EBVaGC or EBVnGC were assessed by univariate and multivariate analysis. Results We found that both STING and PD-L1 exhibited significantly higher expression in the EBVaGCs than that in the EBVnGCs. The expression of STING was positively correlated with that of PD-L1 in EBVaGCs. Simultaneous negative expression of STING and PD-L1, and positive expression of STING were independent prognostic risk factors for EBVaGC and EBVnGC, respectively. Conclusions This is the first prognostic retrospective study of STING and PD-L1 expression and the prognosis among EBVaGC and EBVnGC. The expression and prognostic value of STING and PD-L1 are different in the two types of GCs. STING and PD-L1 are promising prognostic biomarkers and therapeutic targets for EBVaGC and EBVnGC.

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“…EBV-GC is almost all adenocarcinoma, and a special histopathological variant is gastric carcinoma with lymphoid stroma (GCLS), which has abundant lymphocytes infiltrating within and around the tumor cells. Patients with GCLS have a relatively better prognosis than those with conventional gastric adenocarcinoma [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Epstein–Barr virus-associated gastric adenosquamous carcinoma with concurrent gastric carcinoma with lymphoid stroma: a case report and review of the literature

et al. 2022

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Background Adenosquamous carcinoma (ASC)with concurrent gastric carcinoma with lymphoid stroma (GCLS) are extremely rare tumors. There are only limited cases reported in the literature. Epstein–Barr virus (EBV) infection was found in the concomitant GCLS, but none in the ASC. Here, we report the first case of gastric cancer with EBV infection detected in both ASC and GCLS. Case presentation A 59-year-old man complained of intermittent upper abdominal pain. The gastric endoscopy revealed a type IIc tumor located in the gastric body near the fundus of the stomach. Histological examination of the gastric tumor showed the coexistence of ASC and GCLS. Both components were positive for EBV-encoded RNA (EBER) in situ hybridization. Neoplastic nests of the former were positive for p63, p40 and CK5/6. The glandular components showed positive acid mucus in the Alcian-blue periodic-acid-schiff (AB-PAS) staining. There was significant difference in the expression of epidermal growth factor receptor (EGFR) between adenocarcinoma and squamous carcinoma, but not in other proteins such as human epidermal growth factor receptor 2 (HER2), p53 and mismatch repair proteins. The role of EGFR signaling pathway needs to be further explored in the differentiation of squamous carcinoma in the gastric ASC. Finally, a diagnosis of early EBV associated gastric ASC with concurrent GCLS (pT1bN1) was made. The patient took a single-drug S1 periodically for half a year after the surgery and has been disease free during 8 months of medical follow-up. Conclusions This is the first case of EBV associated gastric ASC with concurrent GCLS, and pathologists and clinicians should recognize and pay attention to this type of tumor.

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Clinicopathological Features and Prognostic Implication of Gastric Carcinoma with Lymphoid Stroma

Cited by 8 publications

References 43 publications

PD-L1 evaluation in the gastrointestinal tract: from biological rationale to its clinical application

PD-L1 evaluation in the gastrointestinal tract: from biological rationale to its clinical application

Prognostic Perspectives of STING and PD-L1 Expression and Correlation with the Prognosis of Epstein-Barr Virus-Associated Gastric Cancers

Epstein–Barr virus-associated gastric adenosquamous carcinoma with concurrent gastric carcinoma with lymphoid stroma: a case report and review of the literature

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