Retrospective study on the correlation between 18‐fluorodeoxyglucose uptake in positron emission tomography–computer tomography and tumour volume, cytological activity as assessed with Ki‐67 and <scp>GLUT</scp>‐1 staining in 10 cases of Merkel cell carcinoma

Kitamura, Shinya; Yanagi, Teruki; Inamura-Takashima, Y.; Imafuku, Kimiaki; Hata, Hiroyuki; Uehara, Jiro; Ishida, Yoshihiro; Otsuka, Atsushi; Hirata, Kenji; Shimizu, Hiroshi

doi:10.1111/jdv.14821

Cited by 5 publications

(6 citation statements)

References 10 publications

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“…Glut‐1 expression in both groups was predominantly found in the peripheral parts of the tumours. Besides our study, there is only one study on Glut‐1 expression in MCC showing that Glut‐1 expression (ranging from 10% to 86.7% of tumour cells) was positively correlated with fluorodeoxyglucose uptake in positron emission tomography 15 . Our data provide evidence that HIF‐1α‐induced upregulation of Glut‐1 contributes to metabolic reprogramming in MCC; further studies focusing on Glut‐1 expression in MCC and its prognostic impact are thus warranted.…”

Section: Discussionmentioning

confidence: 53%

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Metabolic reprogramming and angiogenesis in primary cutaneous Merkel cell carcinoma: expression of hypoxia‐inducible factor‐1α and its central downstream factors

Toberer

Haenssle

Heinzel‐Gutenbrunner

et al. 2020

Acad Dermatol Venereol

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BackgroundMetabolic reprogramming and altered gene expression mediated by hypoxia‐inducible factors play crucial roles during tumour growth and progression. Nevertheless, studies analysing the expression of hypoxia‐inducible factor‐1α and its downstream targets in Merkel cell carcinoma (MCC) are lacking but are warranted to shed more light on MCC pathogenesis and to potentially provide new therapeutic options.ObjectivesTo analyse the immunohistochemical expression of hypoxia‐inducible factor‐1α (HIF‐1α), vascular endothelial growth factor‐A (referred to as VEGF throughout the manuscript), VEGF receptor‐2 (VEGFR‐2), VEGF receptor‐3 (VEGFR‐3), glucose transporter‐1 (Glut‐1), monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CAIX) in primary cutaneous MCC.MethodsThe 16 paraffin‐embedded primary cutaneous MCCs (Merkel cell polyomavirus (McPyV) positive/negative: 11/5) were analysed by immunohistochemistry, namely HIF‐1α, VEGF, VEGFR‐2 (KDR), VEGFR‐3 (FLT4), Glut‐1, MCT4 and CAIX. An established quantification score (QS) was applied to quantitate the protein expression by considering the percentage of positive tumour cells (0: 0%; 1: up to 1%; 2: 2–10%; 3: 11–50%; 4: >50%) in relation to the staining intensity (0: negative; 1: low; 2: medium; 3: strong).ResultsHIF‐1α was expressed in all MCCs and predominantly found at the invading edges of tumour margins. The HIF‐1α downstream factors Glut‐1, MCT4 and CAIX were expressed in 13 of 16 MCC (81%), 14 of 16 MCC (88%) and 16 of 16 MCC (100%), respectively. Interestingly, VEGF and VEGFR‐2 were not expressed in tumour cells, whereas VEGFR‐3 was expressed in all MCCs. HIF‐1α was expressed significantly stronger in McPyV+ tumours (QS: 10.36 ± 2.41) than in McPyV− tumours (QS: 5.40 ± 1.34; P = 0.002). Similarly, VEGFR‐3 was also expressed significantly stronger in McPyV+ tumours (QS: 10.00 ± 2.52) than in McPyV− tumours (QS: 5.40 ± 3.43, P = 0.019).ConclusionsOur data provide first evidence for a role of HIF‐1α in induced metabolic reprogramming contributing to MCC pathogenesis. The metabolic signatures of McPyV+ and McPyV− tumours seem to show relevant differences.

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Section: Discussionmentioning

confidence: 53%

“…Several studies have examined Glut‐1 expression in melanocytic nevi and melanoma as well as in non‐melanoma skin cancer 3,12‐14 . However, there is only one immunohistochemical study on record that has analysed Glut‐1 expression in MCC 15 …”

Section: Introductionmentioning

confidence: 99%

Metabolic reprogramming and angiogenesis in primary cutaneous Merkel cell carcinoma: expression of hypoxia‐inducible factor‐1α and its central downstream factors

Toberer

Haenssle

Heinzel‐Gutenbrunner

et al. 2020

Acad Dermatol Venereol

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“…The current pilot study had several limitations: (1) In our study, we selected 18F-FDG PET/CT scans as a candidate parameter to elucidate the link between cytogenetics/genomics and imaging patterns in RRMM. While 18F-FDG clearly is the standard of reference tracer in nuclear imaging of MM, scan results might be influenced by different factors, such as expression levels of hexokinase-2 and glucose transporter, as well as hyperglycemia, and false-positive results due to infection, chronic inflammation, metallic implants, surgery, and fracture healing can occur [ 2 , 19 , 20 , 21 , 22 ]. In this context, the hexokinase-2 expression is increased in the HY and PR molecular subgroup [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

The Link between Cytogenetics/Genomics and Imaging Patterns of Relapse and Progression in Patients with Relapsed/Refractory Multiple Myeloma: A Pilot Study Utilizing 18F-FDG PET/CT

Zhou

Dierks

Kertels

et al. 2020

Cancers

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Utilizing 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT), we performed this pilot study to evaluate the link between cytogenetic/genomic markers and imaging patterns in relapsed/refractory (RR) multiple myeloma (MM). We retrospectively analyzed data of 24 patients with RRMM who were treated at our institution between November 2018 and February 2020. At the last relapse/progression, patients had been treated with a median of three (range 1–10) lines of therapy. Six (25%) patients showed FDG avid extramedullary disease without adjacency to bone. We observed significantly higher maximum standardized uptake values (SUVmax) in patients harboring del(17p) compared with those without del(17p) (p = 0.025). Moreover, a high SUVmax of >15 indicated significantly shortened progression-free survival (PFS) (p = 0.01) and overall survival (OS) (p = 0.0002). One female patient exhibited biallelic TP53 alteration, i.e., deletion and mutation, in whom an extremely high SUVmax of 37.88 was observed. In summary, this pilot study suggested a link between del(17p)/TP53 alteration and high SUVmax on 18F-FDG PET/CT in RRMM patients. Further investigations are highly warranted at this point.

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“…After thorough review and exclusion due to doublets, review articles, case reports, non-English publications, and articles, which not contain correlation coefficients between PET and GLUT, 53 articles were suitable for the meta analysis [19–69]. In these articles 56 patient samples were acquired.…”

Section: Methodsmentioning

confidence: 99%

“…In most studies, GLUT 1 was investigated. Previously, some studies identified a strong positive correlation between GLUT expression and SUV values derived from FDG-PET, as it is hypothetically expected [19, 20]. However, there are also studies, which could not show any significant associations between SUV and GLUT [21].…”

Section: Introductionmentioning

confidence: 95%

Associations between GLUT expression and SUV values derived from FDG-PET in different tumors—A systematic review and meta analysis

2019

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Purpose Fluorodeoxyglucose-Positron-emission tomography (FDG-PET), quantified by standardized uptake values (SUV), is one of the most used functional imaging modality in clinical routine. It is widely acknowledged to be strongly associated with Glucose-transporter family (GLUT)-expression in tumors, which mediates the glucose uptake into cells. The present systematic review sought to elucidate the association between GLUT 1 and 3 expression with SUV values in various tumors. Methods MEDLINE library was screened for associations between FDG-PET parameters and GLUT correlation cancer up to October 2018. Results There were 53 studies comprising 2291 patients involving GLUT 1 expression and 11 studies comprising 405 patients of GLUT 3 expression. The pooled correlation coefficient for GLUT 1 was r = 0.46 (95% CI 0.40–0.52), for GLUT 3 was r = 0.35 (95%CI 0.24–0.46). Thereafter, subgroup analyses were performed. The highest correlation coefficient for GLUT 1 was found in pancreatic cancer r = 0.60 (95%CI 0.46–0.75), the lowest was identified in colorectal cancer with r = 0.21 (95% CI -0.57–0.09). Conclusion An overall only moderate association was found between GLUT 1 expression and SUV values derived from FDG-PET. The correlation coefficient with GLUT 3 was weaker. Presumably, the underlying mechanisms of glucose hypermetabolism in tumors are more complex and not solely depended on the GLUT expression.

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Retrospective study on the correlation between 18‐fluorodeoxyglucose uptake in positron emission tomography–computer tomography and tumour volume, cytological activity as assessed with Ki‐67 and GLUT‐1 staining in 10 cases of Merkel cell carcinoma

Cited by 5 publications

References 10 publications

Metabolic reprogramming and angiogenesis in primary cutaneous Merkel cell carcinoma: expression of hypoxia‐inducible factor‐1α and its central downstream factors

Metabolic reprogramming and angiogenesis in primary cutaneous Merkel cell carcinoma: expression of hypoxia‐inducible factor‐1α and its central downstream factors

The Link between Cytogenetics/Genomics and Imaging Patterns of Relapse and Progression in Patients with Relapsed/Refractory Multiple Myeloma: A Pilot Study Utilizing 18F-FDG PET/CT

Associations between GLUT expression and SUV values derived from FDG-PET in different tumors—A systematic review and meta analysis

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