The role of glutamate decarboxylase 65 in gastric cancer development, progression, and prognosis

Song, Yongxi; Li, Shizheng; Wang, Zhenning; Zhu, Junjie; Gao, Peng; Wang, Meixian; Dong, Yulan; Xu, Hui

doi:10.1111/his.12164

Cited by 4 publications

(3 citation statements)

References 22 publications

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“…That only few other tumor entities contained (weakly) GAD2-positive cases in <10% of cases fit well with the summarized data from the The Cancer Genome Atlas database where only very few nonpancreatic neoplasms displayed detectable but very low-level GAD2 RNA expression ( https://www.proteinatlas.org/ENSG00000136750-GAD2/summary/rna ). It is of note that other authors have described immunohistochemical GAD2 positivity in 71% of 313 gastric cancers, 12 55% of 108 adenocarcinomas of the gallbladder, 13 and in 30% of 46 parathyroidal adenomas. 13 However, GAD2 immunostaining was only observed in 1 (0.2%) of 467 gastric and 1 (2%) of 49 gallbladder adenocarcinomas.…”

Section: Discussionmentioning

confidence: 79%

“…Only a few authors have examined GAD2 expression in cancer and proposed a role for tumor progression in gastric and gallbladder cancer. Song et al 12 reported a significantly higher GAD65 expression in 313 gastric cancers than in 60 adjacent nontumor tissues and found a link between high expression and the depth of tumor invasion, high TNM stage, and poor prognosis. For gallbladder adenocarcinoma, Deng and Pei 13 found increased levels of GAD65 immunostaining as compared with peritumoral tissues and a significant link between high GAD65 expression and reduced patient survival.…”

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confidence: 99%

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GAD2 Is a Highly Specific Marker for Neuroendocrine Neoplasms of the Pancreas

Lennartz,

Benjamin Dünnebier,

Höflmayer

et al. 2024

American Journal of Surgical Pathology

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Glutamate decarboxylase 2 (GAD2) is the most important inhibitory neurotransmitter and plays a role in insulin-producing β cells of pancreatic islets. The limitation of GAD2 expression to a few normal cell types makes GAD2 a potential immunohistochemical diagnostic marker. To evaluate the diagnostic utility of GAD2 immunohistochemistry, a tissue microarray containing 19,202 samples from 152 different tumor entities and 608 samples of 76 different normal tissue types was analyzed. In normal tissues, GAD2 staining was restricted to brain and pancreatic islet cells. GAD2 staining was seen in 20 (13.2%) of 152 tumor categories, including 5 (3.3%) tumor categories containing at least 1 strongly positive case. GAD2 immunostaining was most commonly seen in neuroendocrine carcinomas (58.3%) and neuroendocrine tumors (63.2%) of the pancreas, followed by granular cell tumors (37.0%) and neuroendocrine tumors of the lung (11.1%). GAD2 was only occasionally (<10% of cases) seen in 16 other tumor entities including paraganglioma, medullary thyroid carcinoma, and small cell neuroendocrine carcinoma of the urinary bladder. Data on GAD2 and progesterone receptor (PR) expression (from a previous study) were available for 95 pancreatic and 380 extrapancreatic neuroendocrine neoplasms. For determining a pancreatic origin of a neuroendocrine neoplasm, the sensitivity of GAD2 was 64.2% and specificity 96.3%, while the sensitivity of PR was 56.8% and specificity 92.6%. The combination of PR and GAD2 increased both sensitivity and specificity. GAD2 immunohistochemistry is a highly useful diagnostic tool for the identification of pancreatic origin in case of neuroendocrine neoplasms with unknown site of origin.

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Section: Discussionmentioning

confidence: 79%

mentioning

confidence: 99%

GAD2 Is a Highly Specific Marker for Neuroendocrine Neoplasms of the Pancreas

Lennartz,

Benjamin Dünnebier,

Höflmayer

et al. 2024

American Journal of Surgical Pathology

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“…The expression levels of GAD65 significantly correlate with the depth of tumor invasion and advanced TNM stage in gastric cancer and thus may be useful for reclassifying tumor growth patterns (9). In a clinicopathological study of benign and malignant lesions in the gallbladder, the expression level of GAD65 was significantly higher in the gallbladder adenocarcinoma than in the peritumoral tissues, adenomatous polyps, or areas of chronic cholecystitis.…”

Section: Discussionmentioning

confidence: 99%

Small Cell Lung Cancer Expressing Glutamate Decarboxylase with Latent Autoimmune Diabetes in Adults

et al. 2015

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Small cell lung cancer (SCLC) causes paraneoplastic syndromes, such as diabetes mellitus, by eliciting the expression of various antibodies including anti-glutamate decarboxylase (GAD) antibody. A 62-year-old woman presented to our hospital with a 1-week history of progressive dyspnea and difficulty in walking. Computed tomography showed a tumor obstructing the left bronchus and obstructive lung abscesses with pleural effusions. A biopsy during bronchoscopy revealed SCLC, and the clinical stage was ultimately determined to be IIIB. SCLC was complicated by diabetes mellitus with high titers of serum anti-GAD antibody. An immunohistochemical analysis showed GAD expression in the cancer cells, which is a novel finding.

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