scholarly journals Glucose transporter Glut-1 is detectable in peri-necrotic regions in many human tumor types but not normal tissues: Study using tissue microarrays

2010 ◽  
Vol 192 (3) ◽  
pp. 133-138 ◽  
Author(s):  
Rachel Airley ◽  
Andrew Evans ◽  
Ali Mobasheri ◽  
Stephen M. Hewitt
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.


Sarcoma ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Eivind Smeland ◽  
Thomas K. Kilvaer ◽  
Sveinung Sorbye ◽  
Andrej Valkov ◽  
Sigve Andersen ◽  
...  

Background.We aimed to explore the prognostic impact of the hypoxia-induced factors (HIFαs) 1 and 2, the metabolic HIF-regulated glucose transporter GLUT-1, and carbonic anhydrase IX (CAIX) in non-gastrointestinal stromal tumor soft tissue sarcomas (non-GIST STS).Methods.Duplicate cores with viable tumor tissue from 206 patients with non-GIST STS were obtained and tissue microarrays were constructed. Immunohistochemistry (IHC) was used to evaluate expression of hypoxic markers.Results.In univariate analyses, GLUT-1 (P<0.001) and HIF-2α (P=0.032) expression correlated significantly with a poor disease-specific survival (DSS). In the multivariate analysis, however, only high expression of GLUT-1 (HR 1.7, CI 95% 1.1–2.7,P=0.021) was a significant independent prognostic indicator of poor DSS.Conclusion.GLUT-1 is a significant independent negative prognostic factor in non-GIST STS.


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Stefan Steurer ◽  
Claudia Riemann ◽  
Franziska Büscheck ◽  
Andreas M. Luebke ◽  
Martina Kluth ◽  
...  

Abstract Background Tumor protein 63 (p63) is a transcription factor of the p53 gene family involved in differentiation of several tissues including squamous epithelium. p63 immunohistochemistry is broadly used for tumor classification but published data on its expression in cancer is conflicting. Methods To comprehensively catalogue p63 expression, tissue microarrays (TMAs) containing 12,620 tissue samples from 115 tumor entities and 76 normal tissue types were analyzed. Results p63 expression was seen in various normal tissues including squamous epithelium and urothelium. At least occasional weak p63 positivity could be detected in 61 (53%) of 115 different tumor types. The frequencies of p63 positivity was highest in squamous cell carcinomas irrespective of their origin (96–100%), thymic tumors (100%), urothelial carcinomas (81–100%), basal type tumors such as basal cell carcinomas (100%), and various salivary gland neoplasias (81–100%). As a rule, p63 was mostly expressed in cancers derived from p63 positive normal tissues and mostly not detectable in tumors derived from p63 negative cancers. However, exceptions from this rule occurred. A positive p63 immunostaining in cancers derived from p63 negative tissues was unrelated to aggressive phenotype in 422 pancreatic cancers, 160 endometrium cancers and 374 ovarian cancers and might be caused by aberrant squamous differentiation or represent stem cell properties. In 355 gastric cancers, aberrant p63 expression occurred in 4% and was linked to lymph node metastasis (p = 0.0208). Loss of p63 in urothelial carcinomas - derived from p63 positive urothelium - was significantly linked to advanced stage, high grade (p < 0.0001 each) and poor survival (p < 0.0001) and might reflect clinically relevant tumor dedifferentiation. Conclusion The high prevalence of p63 expression in specific tumor types makes p63 immunohistochemistry a suitable diagnostic tool. Loss of p63 expression might constitute a feature of aggressive cancers.


2012 ◽  
Vol 136 (7) ◽  
pp. 804-809 ◽  
Author(s):  
Stephen M. Lagana ◽  
Robert N. Taub ◽  
Alain C. Borczuk

Context.—Malignant mesothelioma, of either peritoneum or pleura, is an uncommon cancer. The diagnosis is often difficult to make, in part because of the overlapping morphology of reactive and malignant mesothelial cells. Glucose transporter 1 (GLUT-1) is a glucose transporter typically found on erythrocytes, which is aberrantly expressed in various carcinomas. It has recently been reported as specific and sensitive in discriminating malignant pleural mesothelioma from reactive hyperplasia. The application of GLUT-1 staining in peritoneal mesothelioma has not been fully explored. Objective.—To determine if GLUT-1 staining is helpful in distinguishing abdominal mesotheliomas from benign, reactive mesothelial lesions and to further study its utility in the thorax. Design.—Tissue microarrays containing 135 abdominal malignant mesotheliomas and 30 malignant pleural mesotheliomas were stained with an antibody to GLUT-1, as were 56 reactive mesothelial lesions. Results.—The overall sensitivity and specificity for GLUT-1 in mesothelioma was 53% and 98%, respectively. The sensitivity in epithelioid malignant mesothelioma was 49% and in sarcomatoid/biphasic malignant mesothelioma, 66%. In the thorax, the sensitivity was 50% and in the abdomen it was 54%. The positive predictive value of GLUT-1 immunoreactivity was 98% and the negative predictive value was 40%. Conclusion.—Glucose transporter 1 staining of thoracic mesotheliomas showed high specificity but lower sensitivity than previously reported. Abdominal malignant mesotheliomas showed similar results. Because of low sensitivity, only positive staining is informative. In both sites, the utility of the stain was limited by nonspecific staining (eg, in necrotic areas) as well as bright labeling of erythrocytes and occasional lymphoid elements. Despite these limitations, GLUT-1 can help differentiate malignant mesothelioma from reactive benign mesothelium.


Science ◽  
2020 ◽  
Vol 368 (6494) ◽  
pp. 973-980 ◽  
Author(s):  
Deborah Nejman ◽  
Ilana Livyatan ◽  
Garold Fuks ◽  
Nancy Gavert ◽  
Yaara Zwang ◽  
...  

Bacteria were first detected in human tumors more than 100 years ago, but the characterization of the tumor microbiome has remained challenging because of its low biomass. We undertook a comprehensive analysis of the tumor microbiome, studying 1526 tumors and their adjacent normal tissues across seven cancer types, including breast, lung, ovary, pancreas, melanoma, bone, and brain tumors. We found that each tumor type has a distinct microbiome composition and that breast cancer has a particularly rich and diverse microbiome. The intratumor bacteria are mostly intracellular and are present in both cancer and immune cells. We also noted correlations between intratumor bacteria or their predicted functions with tumor types and subtypes, patients’ smoking status, and the response to immunotherapy.


Author(s):  
Joseph M. Harb ◽  
James T. Casper ◽  
Vlcki Piaskowski

The application of tissue culture and the newer methodologies of direct cloning and colony formation of human tumor cells in soft agar hold promise as valuable modalities for a variety of diagnostic studies, which include morphological distinction between tumor types by electron microscopy (EM). We present here two cases in which cells in culture expressed distinct morphological features not apparent in the original biopsy specimen. Evaluation of the original biopsies by light and electron microscopy indicated both neoplasms to be undifferentiated sarcomas. Colonies of cells propagated in soft agar displayed features of rhabdomyoblasts in one case, and cultured cells of the second biopsy expressed features of Ewing's sarcoma.


2019 ◽  
Vol 26 (11) ◽  
pp. 1994-2050 ◽  
Author(s):  
Annamaria Sandomenico ◽  
Menotti Ruvo

Background:Elucidating the mechanisms of recurrence of embryonic signaling pathways in tumorigenesis has led to the discovery of onco-fetal players which have physiological roles during normal development but result aberrantly re-activated in tumors. In this context, Nodal and Cripto-1 are recognized as onco-developmental factors, which are absent in normal tissues but are overexpressed in several solid tumors where they can serve as theranostic agents.Objective:To collect, review and discuss the most relevant papers related to the involvement of Nodal and Cripto-1 in the development, progression, recurrence and metastasis of several tumors where they are over-expressed, with a particular attention to their occurrence on the surface of the corresponding sub-populations of cancer stem cells (CSC).Results:We have gathered, rationalized and discussed the most interesting findings extracted from some 370 papers related to the involvement of Cripto-1 and Nodal in all tumor types where they have been detected. Data demonstrate the clear connection between Nodal and Cripto-1 presence and their multiple oncogenic activities across different tumors. We have also reviewed and highlighted the potential of targeting Nodal, Cripto-1 and the complexes that they form on the surface of tumor cells, especially of CSC, as an innovative approach to detect and suppress tumors with molecules that block one or more mechanisms that they regulate.Conclusion:Overall, Nodal and Cripto-1 represent two innovative and effective biomarkers for developing potential theranostic anti-tumor agents that target normal as well as CSC subpopulations and overcome both pharmacological resistance and tumor relapse.


2012 ◽  
Vol 24 (2) ◽  
pp. 344 ◽  
Author(s):  
M. Garcia-Herreros ◽  
I. M. Aparicio ◽  
D. Rath ◽  
T. Fair ◽  
P. Lonergan

Previous studies have shown that developmental kinetic rates following IVF are lower in female than in male blastocysts and that this may be related to differences in glucose metabolism. In addition, an inhibition of phosphatidylinositol 3-kinase (PI3-K) inhibits glucose uptake in murine blastocysts. Therefore, the aim of this study was to identify and compare the expression of proteins involved in glucose metabolism (hexokinase-I, HK-I; phosphofructokinase-1, PFK-1; pyruvate kinase1/2, PK1/2; glyceraldehyde-3-phosphate dehydrogenase, GAPDH; glucose transporter-1, GLUT-1; and glycogen synthase kinase-3, GSK-3) in male and female bovine blastocysts to determine whether PI3-K has a role in the regulation of the expression of these proteins. Hexokinase-I, PFK-1, PK1/2, GAPDH and GLUT-1 were present in bovine embryos. Protein expression of these proteins and GSK-3 was significantly higher in male compared with female blastocysts. Inhibition of PI3-K with LY294002 significantly decreased the expression of HK-I, PFK-1, GAPDH, GSK-3 A/B and GLUT-1. Results showed that the expression of glycolytic proteins HK-I, PFK-1, GAPDH and PK1/2, and the transporters GLUT-1 and GSK-3 is regulated by PI3-K in bovine blastocysts. Moreover, the differential protein expression observed between male and female blastocysts might explain the faster developmental kinetics seen in males, as the expression of main proteins involved in glycolysis and glycogenogenesis was significantly higher in male than female bovine embryos and also could explain the sensitivity of male embryos to a high concentration of glucose, as a positive correlation between GLUT-1 expression and glucose uptake in embryos has been demonstrated.


1994 ◽  
Vol 269 (32) ◽  
pp. 20482-20488 ◽  
Author(s):  
R.C. Hresko ◽  
M. Kruse ◽  
M. Strube ◽  
M. Mueckler
Keyword(s):  

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