scholarly journals Large-Scale Tissue Microarray Evaluation Corroborates High Specificity of High-Level Arginase-1 Immunostaining for Hepatocellular Carcinoma

Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2351
Author(s):  
Maximilian Lennartz ◽  
Eva Gehrig ◽  
Sören Weidemann ◽  
Natalia Gorbokon ◽  
Anne Menz ◽  
...  

Arginase-1 catalyzes the conversion of arginine to ornithine and urea. Because of its predominant expression in hepatocytes, it serves as a marker for hepatocellular carcinoma, although other tumor entities can also express arginase-1. To comprehensively determine arginase-1 expression in normal and neoplastic tissues, tissue microarrays containing 14,912 samples from 117 different tumor types and 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. In normal tissues, arginase-1 was expressed in the liver, the granular layer of the epidermis, and in granulocytes. Among tumors, a nuclear and cytoplasmic arginase-1 immunostaining was predominantly observed in hepatocellular carcinoma, where 96% of 49 cancers were at least moderately positive. Although 22 additional tumor categories showed occasional arginase immunostaining, strong staining was exceedingly rare in these entities. Staining of a few tumor cells was observed in squamous cell carcinomas of various sites. Staining typically involved maturing cells with the beginning of keratinization in these tumors and was significantly associated with a low grade in 635 squamous cell carcinomas of various sites (p = 0.003). Teratoma, urothelial carcinoma and pleomorphic adenomas sometimes also showed arginase expression in areas with squamous differentiation. In summary, arginase-1 immunohistochemistry is highly sensitive and specific for hepatocellular carcinoma if weak and focal staining is disregarded.

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Simon Kind ◽  
Christina Merenkow ◽  
Franziska Büscheck ◽  
Katharina Möller ◽  
David Dum ◽  
...  

Syndecan-1 (CD138) is a transmembrane proteoglycan known to be expressed in various normal and malignant tissues. It is of interest because of a possible prognostic role of differential expression in tumors and its role as a target for indatuximab, a monoclonal antibody coupled with a cytotoxic agent. To comprehensively analyze CD138 in normal and neoplastic tissues, we used tissue microarrays (TMAs) for analyzing immunohistochemically detectable CD138 expression in 2,518 tissue samples from 85 different tumor entities and 76 different normal tissue types. The data showed that CD138 expression is abundant in tumors. At least an occasional weak CD138 immunostaining could be detected in 71 of 82 (87%) different tumor types, and 58 entities (71%) had at least one tumor with a strong positivity. In normal tissues, a particularly strong expression was found in normal squamous epithelium of various organs, goblet and columnar cells of the gastrointestinal tract, and in hepatocytes. The highly standardized analysis of most human cancer types resulted in a ranking order of tumors according to the frequency and levels of CD138 expression. CD138 immunostaining was highest in squamous cell carcinomas such as from the esophagus (100%), cervix uteri (79.5%), lung (85.7%), vagina (89.7%) or vulva (73.3%), and in invasive urothelial cancer (76.2%). In adenocarcinomas, CD138 was also high in lung (82.9%) and colorectal cancer (85.3%) but often lower in pancreas (73.3%), stomach (54.2% in intestinal type), or prostate carcinomas (16.3%). CD138 expression was usually low or absent in germ cell tumors, sarcomas, endocrine tumors including thyroid cancer, and neuroendocrine tumors. In summary, the preferential expression in squamous cell carcinomas of various sites makes these cancers prime targets for anti-CD138 treatments once these might become available. Abundant expression in many different normal tissues might pose obstacles to exploiting CD138 as a therapeutic target, however.


2010 ◽  
Vol 28 (15_suppl) ◽  
pp. 5548-5548
Author(s):  
W. N. William ◽  
M. Nunez ◽  
X. Gu ◽  
R. W. Jacobs ◽  
A. M. Litvak ◽  
...  

1986 ◽  
Vol 7 (11) ◽  
pp. 1889-1893 ◽  
Author(s):  
Hiroko Ohgaki ◽  
Hirokazu Hasegawa ◽  
Miki Suenaga ◽  
Tamami Kato ◽  
Shigeaki Sato ◽  
...  

2004 ◽  
Vol 203 (3) ◽  
pp. 798-807 ◽  
Author(s):  
Reinhard Ullmann ◽  
Patrizia Morbini ◽  
Iris Halbwedl ◽  
Massimo Bongiovanni ◽  
Margit Gogg-Kammerer ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jingchen Liang ◽  
Duo Wang ◽  
Guanhua Qiu ◽  
Xiaoqi Zhu ◽  
Junjie Liu ◽  
...  

Background. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer that has a high level of morbidity and mortality. Long noncoding RNA (lncRNA) is a novel regulatory factor of tumour proliferation, apoptosis, and metastasis. Our previous studies indicated that lncRNA FOXP4-AS1 is a functional oncogene in HCC; thus, this study is aimed at further evaluating the clinical and biological function of FOXP4-AS1 in HCC. Material and Methods. First, we detected the expression of FOXP4-AS1 in HCC tissues and paracarcinoma normal tissues by qRT-PCR. Second, the prognostic effects of FOXP4-AS1 in patients with HCC were analysed in a training group and a verification group. Subsequently, to investigate the biological effects of FOXP4-AS1 on HCC cells, downexpression tests were further conducted. Results. The expression of FOXP4-AS1 was higher in HCC tissues than adjacent nontumourous tissues, whereas the low expression of FOXP4-AS1 was correlated with optimistic treatment outcomes, which suggested that FOXP4-AS1 may be an independent prognostic biomarker for HCC. Moreover, the downregulation of FOXP4-AS1 significantly reduced the cell proliferation and clonal abilities and inhibited the invasion, migration, and angiogenesis of hepatoma cells ( P < 0.05 ). Conclusion. These results revealed the clinical significance and biological function of FOXP4-AS1 in HCC development, which may provide a new direction for finding therapeutic targets and potential prognostic biomarkers of HCC.


2021 ◽  
Author(s):  
Cosima Völkel ◽  
Noémi De Wispelaere ◽  
Sören Weidemann ◽  
Natalia Gorbokon ◽  
Maximilian Lennartz ◽  
...  

Abstract Cytokeratins (CKs) 5 and 6 are functionally unrelated but often analyzed together using bispecific antibodies in diagnostic immunohistochemistry. To better understand the diagnostic utility of CK5 or CK6 alone, tissue microarrays with > 15,000 samples from 120 different tumor types as well as 608 samples of 76 different normal tissues were analyzed by immunohistochemistry. In normal tissues, both CKs occurred in the squamous epithelium; CK5 dominated in basal and CK6 in suprabasal layers. CK5 (not CK6) stained basal cells in various other organs. Within tumors, both CK5 and CK6 were seen in > 95% of squamous cell carcinomas, but other tumor entities showed different results: CK5 predominated in urothelial carcinoma and mesothelioma, but CK6 in adenocarcinomas. Joint analysis of both CK5 and CK6 obscured the discrimination of epithelioid mesothelioma (100% positive for CK5 alone and for CK5/6) from adenocarcinoma of the lung (12.8% positive for CK5 alone; 23.7% positive for CK5/6). CK5 and CK6 expressions were both linked to high grade, estrogen receptor, and progesterone receptor negativity in breast cancer (p < 0.0001 each), grade/stage progression in urothelial cancer (p < 0.0001), and RAS mutations in colorectal cancer (p < 0.01). Useful diagnostic properties which are commonly attributed to CK5/6 antibodies such as basal cell staining in the prostate, distinction of adenocarcinoma of the lung from squamous cell carcinoma and epithelioid mesothelioma, and identification of basal-type features in urothelial cancer are solely driven by CK5. At least for the purpose of distinguishing thoracic tumors, monospecific CK5 antibodies may be better suited than bispecific CK5/6 antibodies.


Author(s):  
Sven Saussez ◽  
Christine Decaestecker ◽  
Francois Lorfevre ◽  
Diana-Raluca Cucu ◽  
Goeffrey Mortuaire ◽  
...  

Author(s):  
Zahra Asefy ◽  
Sirus Hoseinnejhad ◽  
Aziz Eftekhari ◽  
Behrooz Shoukuhi

Abstract Backgrounds Hepatocellular carcinoma (HCC) is a diversity of hepatocellular neoplasms and is more prevalence in people with chronic liver disease and cirrhosis. It has been revealed that modification in miRNA regulation possibly will be elaborated in HCC pathogenesis. Materials and methods In this research 40 samples of HCC subjects and 40 samples of healthy liver were considered. Total RNA was obtained from paraffin-embedded tissue blocks and miR-515, miR-623 and miR-1272 gene expression levels were quantified by Real-Time Quantitative Reverse Transcription PCR. Likewise, the Notch protein quantity was assayed in ffpe materials by immunohistochemistry. Results Our study disclosed that Notch protein deals was ominously elevated in cancer cells than healthy cells (p<0.05). Data analysis also displayed that miR-515, miR-623 and miR-1272 expression levels were 3.8, 4.7, and 2.9 fold in normal tissues, respectively (p<0.05). Furthermore, it was found that expression levels of these genes are not dependent by hepatitis B and hepatic cirrhosis and it could be used as a marker of high specificity and sensitivity for the diagnosis of HCC. Discussions Our study demonstrated main role of miR-515, miR-623 and miR-1272 in HCC pathogenesis and similarly disclosed that these genes expression could be utilized in HCC prognosis.


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