Dataset Information

Gastric Signet Ring Cell Carcinoma: Current Management and Future Challenges.

ABSTRACT: Recent advances in the epidemiology, pathology, molecular mechanisms, and combined modality therapy (CMT) fields have shown that gastric signet ring cell carcinoma (GSRC) should be considered a distinct cancerous entity. Clinical management of this cancer is challenging, with chemoradioresistance and poor outcomes in advanced stages. Pathological and molecular sets of GSRC demonstrate different features of poor cohesion and differentiation according to the WHO, Japanese Gastric Cancer Association, and Laurén classifications. These features also result in poor response to adjuvant and neoadjuvant chemoradiotherapy. Certain studies of GSRC showed the disputed effectiveness of hyperthermic intraperitoneal chemotherapy and immunotherapy. Our aim was to discuss how an improved understanding of these therapeutic benefits may provide better treatment selection for patients, and therefore improve survival. The challenges in the new understanding of GSRC in routine practice and pathology, and the current limitations of treatment will also be discussed.

SUBMITTER: Li Y

PROVIDER: S-EPMC7478370 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Gastric Signet Ring Cell Carcinoma: Current Management and Future Challenges.

Li Yang Y Zhu Zhikai Z Ma Fuhai F Xue Liyan L Tian Yantao Y

Cancer management and research 20200903

Recent advances in the epidemiology, pathology, molecular mechanisms, and combined modality therapy (CMT) fields have shown that gastric signet ring cell carcinoma (GSRC) should be considered a distinct cancerous entity. Clinical management of this cancer is challenging, with chemoradioresistance and poor outcomes in advanced stages. Pathological and molecular sets of GSRC demonstrate different features of poor cohesion and differentiation according to the WHO, Japanese Gastric Cancer Associatio ...[more]

PMID: 32943931

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Project description:BackgroundAdvanced gastric signet-ring cell carcinoma (SRCC) is a specific type of malignant gastric cancer (GC) with distinct poorer survival. Claudin18.2 (CLDN18.2) is a promising neo-biomarker for the treatment of GC. Clinical trials of CLDN18.2-targeted antibody and T cell-based immunotherapy providing promising prospects for the treatment of GC. The effect of antibody therapy depended on the expression rate of CLDN18.2 has been found in clinical trials. This study aimed to determine the prevalence and the therapeutic value of CLDN18.2 in advanced gastric SRCC.MethodsExpression of CLDN18.2 in 105 formalin-fixed, paraffin-embedded (FFPE) tumor tissues was detected by immunohistochemistry (IHC) and evaluated according to FAST criteria. Next-generation sequencing (NGS) using 416 pan-cancer genes panel was performed to characterize the genomic landscape in 61 advanced gastric SRCC patients. Fisher's exact test was used to determine gene differences in different CLDN18.2 expression levels.ResultsA total number of 105 advanced gastric SRCC samples were analyzed, of which 95.2% (100/105) were positive stained. Moderate-to-strong CLDN18.2 expression was observed in 64.8% (68/105) of all samples. In particularly, 21.0% (22/105) samples had positive staining in more than 90% tumor cells. No significance was found between CLDN18.2 expression and overall survival (OS). NGS results showed that single nucleotide variations (SNVs) could be frequently found in TP53 (26.2%), CDH1 (19.7%), MED12 (18.0%), PKHD1 (18.0%) and ARID1A (11.5%), besides, copy number variations (CNVs) were rich in NOTCH1 (18.0%) and FLT4 (9.8%) in SRCC samples. Moreover, SNVs in GRIN2A was found in 20% of the patients who had CLDN18.2 staining in <40% of tumor cells (P=0.043), indicating CLDN18.2 expression might be related to the aberration of GRIN2A in advanced gastric SRCC.ConclusionsThe highly expressed CLDN18.2 among advanced gastric SRCC patients that we found certified the value of CLDN18.2-targeted therapy in this specific type of GC. In addition, Analyses between CLDN18.2 expression and genetic abnormalities provided novel therapeutic options for advanced gastric SRCC.

Dataset Information

Gastric Signet Ring Cell Carcinoma: Current Management and Future Challenges.

Publications

Gastric Signet Ring Cell Carcinoma: Current Management and Future Challenges.

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