Correlation of hypoxia inducible transcription factor in breast cancer and SUVmax of F-18 FDG PET/CT

Jeong, Young-Ju; Jung, Jae-Won; Cho, Yoon-Young; Park, Sung-Hwan; Oh, Hoon-Kyu; Kang, Sung Min

doi:10.5603/nmr.a2016.0043

Cited by 7 publications

(3 citation statements)

References 27 publications

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“…Regarding the gene under-expression we observed in PET[−] criteria patients, with low [ 18 F]FDG avidity, the lower expression of HIF1A was in concordance with the higher SUVmax detected in patients with BC with high HIF-1A expression [32]. On the other hand, the reduction of glucose metabolism, suggested by the lower expression of genes involved in glucose metabolism, could be justified with the fact that tumor cells can switch their metabolic pathway from glucose to other nutrients such as glutamine [33,34].…”

Section: Discussionsupporting

confidence: 74%

Clinicopathological and molecular predictors of [18F]FDG-PET disease detection in HER2-positive early breast cancer: RESPONSE, a substudy of the randomized PHERGain trial

Llombart-Cussac,

Prat,

Pérez-García

et al. 2024

Eur J Nucl Med Mol Imaging

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Background The PHERGain study (NCT03161353) is assessing early metabolic responses to neoadjuvant treatment with trastuzumab-pertuzumab and chemotherapy de-escalation using a [18Fluorine]fluorodeoxyglucose-positron emission tomography ([18F]FDG-PET) and a pathological complete response-adapted strategy in HER2-positive (HER2+) early breast cancer (EBC). Herein, we present RESPONSE, a PHERGain substudy, where clinicopathological and molecular predictors of [18F]FDG-PET disease detection were evaluated. Methods A total of 500 patients with HER2 + EBC screened in the PHERGain trial with a tumor size > 1.5 cm by magnetic resonance imaging (MRI) were included in the RESPONSE substudy. PET[−] criteria entailed the absence of ≥ 1 breast lesion with maximum standardized uptake value (SUVmax) ≥ 1.5 × SUVmean liver + 2 standard deviation. Among 75 PET[−] patients screened, 21 with SUVmax levels < 2.5 were randomly selected and matched with 21 PET[+] patients with SUVmax levels ≥ 2.5 based on patient characteristics associated with [18F]FDG-PET status. The association between baseline SUVmax and [18F]FDG-PET status ([−] or [+]) with clinicopathological characteristics was assessed. In addition, evaluation of stromal tumor-infiltrating lymphocytes (sTILs) and gene expression analysis using PAM50 and Vantage 3D™ Cancer Metabolism Panel were specifically compared in a matched cohort of excluded and enrolled patients based on the [18F]FDG-PET eligibility criteria. Results Median SUVmax at baseline was 7.2 (range, 1–39.3). Among all analyzed patients, a higher SUVmax was associated with a higher tumor stage, larger tumor size, lymph node involvement, hormone receptor-negative status, higher HER2 protein expression, increased Ki67 proliferation index, and higher histological grade (p < 0.05). [18F]FDG-PET [−] criteria patients had smaller tumor size (p = 0.014) along with the absence of lymph node involvement and lower histological grade than [18F]FDG-PET [+] patients (p < 0.01). Although no difference in the levels of sTILs was found among 42 matched [18F]FDG-PET [−]/[+] criteria patients (p = 0.73), [18F]FDG-PET [−] criteria patients showed a decreased risk of recurrence (ROR) and a lower proportion of PAM50 HER2-enriched subtype than [18F]FDG-PET[+] patients (p < 0.05). Differences in the expression of genes involved in cancer metabolism were observed between [18F]FDG-PET [−] and [18F]FDG-PET[+] criteria patients. Conclusions These results highlight the clinical, biological, and metabolic heterogeneity of HER2+ breast cancer, which may facilitate the selection of HER2+ EBC patients likely to benefit from [18F]FDG-PET imaging as a tool to guide therapy. Trial registration Clinicaltrials.gov; NCT03161353; registration date: May 15, 2017.

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Section: Discussionsupporting

confidence: 74%

Clinicopathological and molecular predictors of [18F]FDG-PET disease detection in HER2-positive early breast cancer: RESPONSE, a substudy of the randomized PHERGain trial

Llombart-Cussac,

Prat,

Pérez-García

et al. 2024

Eur J Nucl Med Mol Imaging

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“…Among the many factors in the tumor microenvironment that modulate the differentiation and function of TILs [ 36 37 38 39 ], the most relevant connection between SUV max and Foxp3 could be hypoxia and acidic conditions. Regarding the former, FDG uptake is upregulated in hypoxic conditions [ 17 40 41 ], and it is well-known that hypoxia modulates immune responses in the tumor microenvironment [ 36 42 ] and promotes proliferation of regulatory T cells [ 18 43 ]. In relation to the latter, high lactate concentrations in the tumor microenvironment have been found to block lactate export in T cells, thereby perturbing the metabolism and function of these cells [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Potential Utility of FDG PET-CT as a Non-invasive Tool for Monitoring Local Immune Responses

et al. 2017

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PurposeThe tumor microenvironment is known to be associated with the metabolic activity of cancer cells and local immune reactions. We hypothesized that glucose metabolism measured by 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission tomography (PET)-computed tomography (CT) (18F-FDG PET-CT) would be associated with local immune responses evaluated according to the presence of tumor infiltrating lymphocytes (TILs).Materials and MethodsWe retrospectively reviewed 56 patients who underwent 18F-FDG PET-CT prior to gastrectomy. In resected tumor specimens, TIL subsets, including cluster of differentiation (CD) 3, CD4, CD8, Forkhead box P3 (Foxp3), and granzyme B, were subjected to immunohistochemical analysis. The prognostic nutritional index (PNI) was calculated as: (10×serum albumin value)+(0.005×peripheral lymphocyte counts). Additionally, the maximum standard uptake value (SUVmax) was calculated to evaluate the metabolic activity of cancer cells.ResultsThe SUVmax was positively correlated with larger tumor size (R=0.293; P=0.029) and negatively correlated with PNI (R=−0.407; P=0.002). A higher SUVmax showed a marginal association with higher CD3 (+) T lymphocyte counts (R=0.227; P=0.092) and a significant association with higher Foxp3 (+) T lymphocyte counts (R=0.431; P=0.009). No other clinicopathological characteristics were associated with SUVmax or TILs. Survival analysis, however, indicated that neither SUVmax nor Foxp3 held prognostic significance.ConclusionsFDG uptake on PET-CT could be associated with TILs, especially regulatory T cells, in gastric cancer. This finding may suggest that PET-CT could be of use as a non-invasive tool for monitoring the tumor microenvironment in patients with gastric cancer.

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“…Hypoxia-inducible transcription factor-1α (HIF-1α) is a known essential transcription factor involved in regulating metabolic functions, which targets several metabolismrelated proteins, and its expression has been associated with breast carcinogenesis and prognosis. Jeong et al 8 assessed the correlation between HIF-1α and SUV max of 18 FDG-PET/CT in patients with invasive ductal BC. SUV max reflected the immunohistochemical expression of HIF-1α and could be used as a good surrogate marker for the prediction of tumor progression in patients with BC.…”

Section: Correlation Among Imaging Parameters and Breast Cancermolecumentioning

confidence: 99%

Correlating imaging parameters with molecular data: An integrated approach to improve the management of breast cancer patients

et al. 2020

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The goal of this review is to provide an overview of the studies aimed at integrating imaging parameters with molecular biomarkers for improving breast cancer patient’s diagnosis and prognosis. The use of diagnostic imaging to extract quantitative parameters related to the morphology, metabolism, and functionality of tumors, as well as their correlation with cancer tissue biomarkers is an emerging research topic. Thanks to the development of imaging biobanks and the technological tools required for extraction of imaging parameters including radiomic features, it is possible to integrate imaging markers with genetic data. This new field of study represents the evolution of radiology–pathology correlation from an anatomic–histologic level to a genetic level, which paves new interesting perspectives for breast cancer management.

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Correlation of hypoxia inducible transcription factor in breast cancer and SUVmax of F-18 FDG PET/CT

Abstract: BACKGROUND:Tumor hypoxia induces the expression of several genes via the hypoxia-inducible transcription factor-1 alpha (HIF-1a). It is associated with the prognosis of several cancers. We studied the immunohistochemical expression of HIF-1a in

Cited by 7 publications

References 27 publications

Clinicopathological and molecular predictors of [18F]FDG-PET disease detection in HER2-positive early breast cancer: RESPONSE, a substudy of the randomized PHERGain trial

Clinicopathological and molecular predictors of [18F]FDG-PET disease detection in HER2-positive early breast cancer: RESPONSE, a substudy of the randomized PHERGain trial

Potential Utility of FDG PET-CT as a Non-invasive Tool for Monitoring Local Immune Responses

Correlating imaging parameters with molecular data: An integrated approach to improve the management of breast cancer patients

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