Immunohistochemical expression of the glucose transporters Glut-1 and Glut-3 in human malignant melanomas and benign melanocytic lesions

Parente, Paola; Coli, Antonella; Massi, Guido; Mangoni, Antonella; Fabrizi, Manuela; Bigotti, Giulio

doi:10.1186/1756-9966-27-34

Cited by 49 publications

(40 citation statements)

References 27 publications

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“…Other laboratories have reported trends between GLUT-1 expression and some melanoma features of increased tumor aggressiveness [104, 105]. However, GLUT-1's role in melanoma progression requires further investigation using large number of specimens as other investigators have reported a decreased frequency of GLUT-1 in aggressive melanomas as compared to melanocytic nevi [106], or have reported variable effects on glucose uptake in melanomas [107-109]. …”

Section: Resultsmentioning

confidence: 99%

The role of melanogenesis in regulation of melanoma behavior: Melanogenesis leads to stimulation of HIF-1α expression and HIF-dependent attendant pathways

Slominski

Kim

Brożyna

et al. 2014

Archives of Biochemistry and Biophysics

191

190

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To study the effect of melanogenesis on HIF-1α expression and attendant pathways, we used stable human and hamster melanoma cell lines in which the amelanotic vs melanotic phenotypes are dependent upon the concentration of melanogenesis precursors in the culture media. The induction of melanin pigmentation led to significant up-regulation of HIF-1α, but not HIF-2α, protein in melanized cells for both lines. Similar upregulation of nuclear HIF-1α was observed in excisions of advanced melanotic vs. amelanotic melanomas. In cultured cells, melanogenesis also significantly stimulated expression of classical HIF-1-dependent target genes involved in angiogenesis and cellular metabolism, including glucose metabolism and stimulation of activity of key enzymes in the glycolytic pathway. Several other stress related genes containing putative HRE consensus sites were also upregulated by melanogenesis, concurrently with modulation of expression of HIF-1-independent genes encoding for steroidogenic emzymes, cytokines and growth factors. Immunohistochemical studies using a large panel of pigmented lesions revealed that higher levels of HIF-1α and GLUT-1 were detected in advanced melanomas in comparison to melanocytic nevi or thin melanomas localized to the skin. However, the effects on overall or disease free survival in melanoma patients were modest or absent for GLUT-1 or for HIF-1α, respectively. In conclusion, induction of the melanogenic pathway leads to robust upregulation of HIF-1-dependent and independent pathways in cultured melanoma cells, suggesting a key role for melanogenesis in regulation of cellular metabolism.

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Section: Resultsmentioning

confidence: 99%

The role of melanogenesis in regulation of melanoma behavior: Melanogenesis leads to stimulation of HIF-1α expression and HIF-dependent attendant pathways

Slominski

Kim

Brożyna

et al. 2014

Archives of Biochemistry and Biophysics

191

190

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“…Tumor cells were considered positive for GLUT1 if the cell membrane staining was no less than that of the erythrocytes in the same section. GLUT1 expression was considered positive in each section if the percentage of tumor cells with positive staining was >10%, as previously reported (7,26,27). Ki-67 staining was evaluated using the labeling index (28,29).…”

Section: Introductionmentioning

confidence: 99%

Impact of GLUT1 and Ki-67 expression on early-stage lung adenocarcinoma diagnosed according to a new international multidisciplinary classification

et al. 2012

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Abstract. High expression levels of glucose transporter isoform 1 (GLUT1) and Ki-67 are reportedly associated with malignancy-related clinicopathological factors in malignant tumors. Recently, a new histological IASLC/ATS/ERS classification for lung adenocarcinoma was proposed. In this study, we investigated the clinicopathological impact of GLUT1 and Ki-67 expression on early-stage lung adenocarcinoma classified according to the IASLC/ATS/ERS classification. One hundred and five patients with completely resected stage IA lung adenocarcinoma were retrospectively classified into two groups, a ʻnon-invasive typeʼ (n=31) or an ʻinvasive typeʼ (n=74), based on the IASLC/ATS/ERS classification. GLUT1 and Ki-67 expression status was evaluated using immunohistochemistry. The epidermal growth factor receptor (EGFR) and KRAS mutation status was determined using PCR-based assays. Positive GLUT1 and Ki-67 expression and EGFR and KRAS mutations were detected in 28 (27%), 33 (31%), 51 (49%) and 5 (8%) cases, respectively. Positive GLUT1 expression was significantly associated with a wildtype EGFR and mutant KRAS status. A multivariate analysis revealed that positive GLUT1 expression was independently associated with the ʻinvasive typeʼ. In multivariate analyses for overall survival (OS) and disease-free survival (DFS), positive Ki-67 and GLUT1 expression was the only independent factor for a poor OS (P=0.012) and DFS (P=0.040), respectively. In addition, when stratified according to the GLUT1 and Ki-67 status, double-positive cases had the poorest DFS and OS times, compared with the other categories. Positive GLUT1 expression is associated with the invasive character of earlystage lung adenocarcinoma and with early disease relapse. Our results strongly suggest that GLUT1 and Ki-67 play important roles in acquiring biological malignant potential in early-stage lung adenocarcinoma.

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“…In that way, the biological behavior of OKC can be comparable to various other benign and malignant neoplasms as outlined by various authors. [22][23][24][25][26] Hence, increased GLUT-1 expression in OKC may be treated as molecular evidence to justify the neoplastic nature of OKC, as demanded by various authors in 2007. 2 On the contrary, the decreased GLUT-1 expression in AM is inviting further debate in this very same context.…”

Section: -26mentioning

confidence: 99%

Glucose Transporter 1 Expression in Odontogenic Keratocyst, Dentigerous Cyst, and Ameloblastoma: An Immunohistochemical Study

Bandyopadhyay

Panda

Ramachandra

et al. 2017

The Journal of Contemporary Dental Practice

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Introduction: An array of odontogenic lesions manifest in the maxillofacial region with variable presentations. The biological behavior of lesions, such as odontogenic keratocyst (OKC), dentigerous cyst (DC), and ameloblastoma (AM) always invite debate. Glucose transporter 1 (GLUT-1) is proven to be an indicator of metabolic behavior of several benign and malignant neoplasms. Aim:The purpose of this study was to evaluate the expression of GLUT-1 in OKC, DC, and AM to understand their metabolic behavior. Materials and methods:Immunohistochemical expression of GLUT-1 was evaluated in each of the 15 cases of OKC, DC, and AM. The number of labeled cells, staining intensity, and membrane or cytoplasmic expressions were the parameters assessed and analyzed using chi-square test.Results: All cases showed positive GLUT-1 expression: 86.6% OKC showed more than 50% labeled cells followed by DC (40%) and AM (26.5%); 53.3% OKC showed strong intensity in comparison to AM, which showed weak intensity in 53.3% cases; 86.6% of OKCs showed both membrane and cytoplasmic expression followed by DC (40%) and AM (26.6%), whereas 73.3% of AM showed only membrane expression followed by DC (60%) and OKC (13.3%). Conclusion:Odontogenic keratocyst was found out to be more metabolically active followed by DC and AM.

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Immunohistochemical expression of the glucose transporters Glut-1 and Glut-3 in human malignant melanomas and benign melanocytic lesions

Cited by 49 publications

References 27 publications

The role of melanogenesis in regulation of melanoma behavior: Melanogenesis leads to stimulation of HIF-1α expression and HIF-dependent attendant pathways

The role of melanogenesis in regulation of melanoma behavior: Melanogenesis leads to stimulation of HIF-1α expression and HIF-dependent attendant pathways

Impact of GLUT1 and Ki-67 expression on early-stage lung adenocarcinoma diagnosed according to a new international multidisciplinary classification

Glucose Transporter 1 Expression in Odontogenic Keratocyst, Dentigerous Cyst, and Ameloblastoma: An Immunohistochemical Study

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