Biologic Correlates of 18 Fluorodeoxyglucose Uptake in Human Breast Cancer Measured by Positron Emission Tomography

Han

et al. 2015

Nucl Med Mol Imaging

Purpose The BRAF mutation, a potential prognostic factor in papillary thyroid carcinoma (PTC), is associated with a high expression of the glucose transporter gene. We investigated which clinicopathologic factors, including BRAF mutation status, influence 18 F-fluoro-2-deoxyglucose ( 18 F-FDG) avidity. Methods We retrospectively reviewed 55 patients who underwent BRAF analysis from biopsy-confirmed PTC and 18 F-FDG positron emission tomography/computed tomography within 6 months before undergoing thyroid surgery from September 2008 to August 2014. Tumors were considered to be 18 F-FDG avid if the uptake was greater than that of the liver. 18 F-FDG uptake of PTCs was also analyzed semiquantitatively using SUV max . The association between 18 F-FDG avidity and clinicopathologic variables (age, tumor size, perithyroidal extension, cervical lymph node status, and BRAF mutation status) was investigated. Results Twenty-nine (52.7 %) of 55 patients had 18 F-FDGavid PTCs. PTCs with the BRAF mutation showed higher 18 F-FDG avidity (24/38, 63.2 %) than those without (5/17, 29.4 %). The BRAF mutation (p=0.025) and tumor size (p= 0.003) were significantly associated with 18 F-FDG avidity in univariate analysis, and the BRAF mutation status remained significant after adjusting for tumor size in multivariate analysis (p=0.015). In the subgroup of tumor size≥1 cm, the BRAF mutation was the only factor significantly associated with 18 F-FDG avidity (p=0.021). The mean SUV max of PTCs with the BRAF mutation was significantly higher than that of those without (4.89±6.12 vs. 1.96±1.10, p=0.039). Conclusions The BRAF mutation must be one of the most important factors influencing 18 F-FDG avidity in PTCs, especially in those with a tumor size≥1 cm.

Section: Discussionmentioning

confidence: 99%

Association Between 18F-FDG Avidity and the BRAF Mutation in Papillary Thyroid Carcinoma

Han

et al. 2015

Nucl Med Mol Imaging

“…After deparaffinization and rehydration, the Catalyzed Signal Amplification System (DAKO, Glostrup, Denmark) was used for detecting HIF-1␣, as described previously. 19,34 Briefly, target retrieval solution (DAKO) was used for antigen retrieval with all slides placed in a water bath for 45 minutes at 97°C. A cooling off period of 20 minutes preceded the incubation of the anti-HIF-1␣ mouse monoclonal H1␣ 67 at a dilution of 1:500 (Abcam, Cambridge, United Kingdom).…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…Cytoplasmic VEGF expression was assessed as moderate or strong, as described previously. 34 In the hematoxylin and eosinstained sections, the MAI was counted, as described previously, 32 with a traditional cut-off value of 10/ 1.6 mm 2 . …”

Section: Immunohistochemistrymentioning

confidence: 99%

Levels of hypoxia‐inducible factor‐1α independently predict prognosis in patients with lymph node negative breast carcinoma

Bos

Groep

Greijer

et al. 2003

Cancer

Self Cite

457

361

BACKGROUNDHypoxia‐inducible factor‐1 (HIF‐1) is a transcription factor that plays an important role in tumor growth and metastasis by regulating energy metabolism and inducing angiogenesis to survive cellular hypoxia. Increased levels of HIF‐1α, the O2‐regulated subunit of HIF‐1, were noted during breast carcinogenesis. In this study, the prognostic value of HIF‐1α expression and its correlation with various clinicopathologic variables in patients with invasive breast carcinoma were investigated.METHODSExpression levels of HIF‐1α, HER‐2/neu, estrogen receptor, and progesterone receptor were analyzed in 150 patients with early‐stage breast carcinoma by immunohistochemistry. HER‐2/neu gene amplification was investigated with automated fluorescent in situ hybridization. The mitotic activity index, histologic grade, and tumor type were assessed in hematoxylin and eosinstained specimens. Clinical data included disease‐free survival, overall survival, lymph node status, and tumor size. The data were analyzed with two‐sided univariate and multivariate tests, with P values < 0.05 considered significant.RESULTSHigh levels of HIF‐1α had an association of borderline significance with decreased overall survival (P = 0.059) and disease‐free survival (P = 0.110) that was ascribed completely to the subgroup of women with lymph node negative tumors (n = 81 patients; P = 0.008 and P = 0.004, respectively). HER‐2/neu immunoreactivity (P < 0.001) and gene amplification (P < 0.001), vascular endothelial growth factor expression (P = 0.016), and Ki‐67 expression (P < 0.001) were correlated strongly with HIF‐1α positivity, although none of those factors had an independent effect on survival.CONCLUSIONSIncreased levels of HIF‐1α were associated independently with shortened survival in patients with lymph node negative breast carcinoma. Therefore, the use of immunohistochemical assessment of HIF‐1α as a new predictor of poor outcome may improve clinical decision‐making regarding adjuvant treatment of patients with lymph node negative breast carcinoma. Cancer 2003;97:1573–81. © 2003 American Cancer Society.DOI 10.1002/cncr.11246

“…21,22 Still other cancers, such as breast and thyroid cancers, demonstrate a range of FDG uptake, which may be related to incompletely understood biologic factors. 23 Recent studies have demonstrated that the activation of a variety of oncogenes results in increased FDG uptake. 24 Thus, in many patients, the degree of FDG uptake is a marker of tumor dedifferentiation.…”

Section: Fdg-pet For Cancer Detectionmentioning

confidence: 99%

“…25,26 Because many factors contribute to increased FDG uptake in cancer cells, some studies have suggested that FDG-PET provides a unique measure of tumor biology that is distinct from in vitro assays. 23 False-positive findings are relatively common on FDG-PET, because elevated glycolysis is not limited to cancer cells. 17 Typical causes of increased FDG uptake unrelated to malignancy include infectious and inflammatory etiologies, muscular activity, metabolism in brown fat, and changes in response to bone marrow-stimulating cytokines.…”

Section: Fdg-pet For Cancer Detectionmentioning

confidence: 99%

PET/CT imaging in cancer: Current applications and future directions

Farwell

Pryma

Mankoff

2014

Cancer

183

115

Positron emission tomography (PET) is a radiotracer imaging method that yields quantitative images of regional in vivo biology and biochemistry. PET, now used in conjunction with computed tomography (CT) in PET/CT devices, has had its greatest impact to date on cancer and is now an important part of oncologic clinical practice and translational cancer research. In this review of current applications and future directions for PET/CT in cancer, the authors first highlight the basic principles of PET followed by a discussion of the biochemistry and current clinical applications of the most commonly used PET imaging agent, 18 F-fluorodeoxyglucose (FDG). Then, emerging methods for PET imaging of other biologic processes relevant to cancer are reviewed, including cellular proliferation, tumor hypoxia, apoptosis, amino acid and cell membrane metabolism, and imaging of tumor receptors and other tumor-specific gene products. The focus of the review is on methods in current clinical practice as well as those that have been translated to patients and are currently in clinical trials. Cancer 2014;120:3433-45.