Hepatocellular expression of glutamine synthetase: An indicator of morphogen actions as master regulators of zonation in adult liver

Gebhardt, Rolf; Baldysiak-Figiel, Alicja; Krügel, Vera; Ueberham, Elke; Gaunitz, Frank

doi:10.1016/j.proghi.2006.12.001

Cited by 111 publications

(113 citation statements)

References 302 publications

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“…Glutamine synthetase shows pericentral staining in the normal liver and map-like glutamine synthetase staining in virtually all the cases of focal nodular hyperplasia. 15,25,26 In our study, map-like glutamine synthetase pattern was observed in 90% of focal nodular hyperplasia, but was focal in 17% of cases, all of which were biopsies. In the remaining 10% of focal nodular hyperplasia cases, strong glutamine synthetase staining was observed in patchy groups of hepatocytes without the anastamosing map-like pattern.…”

Section: Discussionmentioning

confidence: 45%

Diagnostic utility and limitations of glutamine synthetase and serum amyloid-associated protein immunohistochemistry in the distinction of focal nodular hyperplasia and inflammatory hepatocellular adenoma

et al. 2014

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Inflammatory hepatocellular adenoma can show overlapping histological features with focal nodular hyperplasia, including inflammation, fibrous stroma, and ductular reaction. Expression of serum amyloidassociated protein in inflammatory hepatocellular adenoma and map-like pattern of glutamine synthetase in focal nodular hyperplasia can be helpful in this distinction, but the pitfalls and limitations of these markers have not been established. Morphology and immunohistochemistry were analyzed in 54 inflammatory hepatocellular adenomas, 40 focal nodular hyperplasia, and 3 indeterminate lesions. Morphological analysis demonstrated that nodularity, fibrous stroma, dystrophic blood vessels, and ductular reaction were more common in focal nodular hyperplasia, while telangiectasia, hemorrhage, and steatosis were more common in inflammatory hepatocellular adenoma, but there was frequent overlap of morphological features. The majority of inflammatory hepatocellular adenomas demonstrated perivascular and/or patchy glutamine synthetase staining (73.6%), while the remaining cases had diffuse (7.5%), negative (3.8%), or patchy pattern of staining (15%) that showed subtle differences from the classic map-like staining pattern and was designated as pseudo map-like staining. Positive staining for serum amyloid-associated protein was seen in the majority of inflammatory hepatocellular adenomas (92.6%) and in the minority of focal nodular hyperplasia (17.5%). The glutamine synthetase staining pattern was map-like in 90% of focal nodular hyperplasia cases, with the remaining 10% of cases showing pseudo map-like staining. Three cases were labeled as indeterminate and showed focal nodular hyperplasia-like morphology but lacked map-like glutamine synthetase staining pattern; these cases demonstrated a patchy pseudo map-like glutamine synthetase pattern along with the expression of serum amyloid-associated protein. Our results highlight the diagnostic errors that can be caused by variant patterns of staining with glutamine synthetase and serum amyloid-associated protein in inflammatory hepatocellular adenoma and focal nodular hyperplasia.

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Section: Discussionmentioning

confidence: 45%

Diagnostic utility and limitations of glutamine synthetase and serum amyloid-associated protein immunohistochemistry in the distinction of focal nodular hyperplasia and inflammatory hepatocellular adenoma

et al. 2014

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“…It plays an important role in ammonia detoxification, nitrogen balance and pH regulation in the liver [4][5][6]. Christa et al [7] demonstrated that levels of GS mRNA, GS protein, and GS activity are upregulated in human HCCs.…”

Section: Introductionmentioning

confidence: 99%

Expression level of glutamine synthetase is increased in hepatocellular carcinoma and liver tissue with cirrhosis and chronic hepatitis B

et al. 2010

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Studies have suggested that glutamine synthetase (GS) is a potential marker of hepatocellular carcinoma (HCC). We aimed to evaluate the expression of GS in non-malignant liver tissue and serum GS levels in HCC, liver cirrhosis (LC), chronic hepatitis B (CHB), five kinds of extrahepatic diseases patients and healthy subjects. Immunohistochemistry (IHC) was used to assess GS expression in 260 liver tissue samples (from 120 HCC, 90 CHB stage 4, and 50 CHB stage 1-3 patients). Enzymelinked immunosorbent assays of 325 samples (from 100 healthy donors, 33 CHB stage 1-3, 43 CHB stage 4, 111 HCC, and 45 extrahepatic diseases patients) were used to further analyze GS levels in serum. IHC studies showed the expression of GS in 70% of HCC patients, 46.7% of CHB stage 4 patients and 38% of CHB stage 1-3 patients. The v 2 tests showed significant difference between HCC samples and non-tumor tissues (P = 0.001 for HCC vs. CHB stage 4, P = 0.000 for HCC vs. CHB). Consistent with this, serum GS levels are increased in HCC and CHB stage 1-4 patients. There are significant differences among all samples (P = 0.000 for all), except CHB stage 1-3 versus CHB stage 4 (P = 0.552). Based on multiple linear regressions, HCC, CHB stage 1-4 and AFP were significantly associated with serum GS levels. In addition, in HCC group, TNM and Child-Pugh were significantly associated with GS levels. Expression of GS is increased in HCC, LC, and CHB. It may be a new serum marker for liver disease.Keywords Glutamine synthetase Á Hepatocellular carcinoma Á Liver cirrhosis Á Chronic hepatitis B Á Regeneration Á Receiver operating characteristic curve Á Sensitivity and specificity Abbreviations

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“…The proliferation of hepatocytes advances from periportal to pericentral areas of the lobule, as a wave of mitoses (Rabes, 1977). Hepatocytes surrounding the central veins (positive for glutamine synthetase (Gebhardt et al, 2007) are the last ones to undergo cell replication. Proliferation of biliary epithelial cells occurs a little later than hepatocytes.…”

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confidence: 99%

Liver regeneration

Michalopoulos

2007

Journal Cellular Physiology

1,315

1,224

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Liver regeneration after partial hepatectomy is a very complex and well-orchestrated phenomenon. It is carried out by the participation of all mature liver cell types. The process is associated with signaling cascades involving growth factors, cytokines, matrix remodeling, and several feedbacks of stimulation and inhibition of growth related signals. Liver manages to restore any lost mass and adjust its size to that of the organism, while at the same time providing full support for body homeostasis during the entire regenerative process. In situations when hepatocytes or biliary cells are blocked from regeneration, these cell types can function as facultative stem cells for each other.

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Hepatocellular expression of glutamine synthetase: An indicator of morphogen actions as master regulators of zonation in adult liver

Cited by 111 publications

References 302 publications

Diagnostic utility and limitations of glutamine synthetase and serum amyloid-associated protein immunohistochemistry in the distinction of focal nodular hyperplasia and inflammatory hepatocellular adenoma

Diagnostic utility and limitations of glutamine synthetase and serum amyloid-associated protein immunohistochemistry in the distinction of focal nodular hyperplasia and inflammatory hepatocellular adenoma

Expression level of glutamine synthetase is increased in hepatocellular carcinoma and liver tissue with cirrhosis and chronic hepatitis B

Liver regeneration

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