[18F]Fluorodeoxyglucose Uptake in Recurrent Thyroid Cancer Is Related to Hexokinase I Expression in the Primary Tumor

Locally advanced thyroid cancer exhibits aggressive clinical features requiring extensive neck dissection. Therefore, it is important to identify changes in the tumor biology before local progression. Here, whole exome sequencing (WES) using tissues from locally advanced papillary thyroid cancer (PTC) presented a large number of single nucleotide variants (SNVs) in the metastatic lymph node (MLN), but not in normal tissues and primary tumors. Among those MLN-specific SNVs, a novel HHIP G516R (G1546A) mutation was also observed. Interestingly, in-depth analysis for exome sequencing data from the primary tumor presented altered nucleotide ‘A’ at a very low frequency indicating intra-tumor heterogeneity between the primary tumor and MLN. Computational prediction models such as PROVEAN and Polyphen suggested that HHIP G516R might affect protein function and stability. In vitro, HHIP G516R increased cell proliferation and promoted cell migration in thyroid cancer cells. HHIP G516R, a missense mutation, could be a representative example for the intra-tumor heterogeneity of locally advanced thyroid cancer, which can be a potential future therapeutic target for this disease.

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Comparison of prognostic values of primary tumor and nodal 18F-fluorodeoxyglucose uptake in non-small cell lung cancer with N1 disease

European Radiology ◽

10.1007/s00330-019-06128-5 ◽

2019 ◽

Vol 29 (10) ◽

pp. 5288-5297

Author(s):

Chae Hong Lim ◽

Seung Hyup Hyun ◽

Seung Hwan Moon ◽

Young Seok Cho ◽

Joon Young Choi ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Primary Tumor ◽

Small Cell ◽

Small Cell Lung ◽

18F Fluorodeoxyglucose

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Transient 18F-Fluorodeoxyglucose Activity on PET/CT of Herniation Pit in Thyroid Cancer Patient: A Case Report

Journal of the Korean Society of Radiology ◽

10.3348/jksr.2017.77.4.249 ◽

2017 ◽

Vol 77 (4) ◽

pp. 249

Author(s):

Yun Hee Kang ◽

Geon Park

Keyword(s):

Thyroid Cancer ◽

Case Report ◽

Cancer Patient ◽

Thyroid Cancer Patient ◽

18F Fluorodeoxyglucose ◽

Pet Ct ◽

Herniation Pit

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Preoperative Serum Thyroglobulin and Its Correlation with the Burden and Extent of Differentiated Thyroid Cancer

Cancers ◽

10.3390/cancers12030625 ◽

2020 ◽

Vol 12 (3) ◽

pp. 625

Author(s):

Hosu Kim ◽

So Young Park ◽

Jun-Ho Choe ◽

Jee Soo Kim ◽

Soo Yeon Hahn ◽

...

Keyword(s):

Thyroid Cancer ◽

Primary Tumor ◽

Differentiated Thyroid Cancer ◽

Medical Center ◽

Distant Metastases ◽

Predictive Biomarker ◽

Tumor Burden ◽

Serum Thyroglobulin ◽

Preoperative Serum ◽

Clinical Records

Lymph node metastasis (LNM) in differentiated thyroid cancer (DTC) is usually detected with preoperative ultrasonography; however, this has limited sensitivity for small metastases, and there is currently no predictive biomarker that can help to inform the extent of surgery required. We evaluated whether preoperative serum thyroglobulin levels can predict tumor burden and extent. We retrospectively reviewed the clinical records of 4029 DTC cases diagnosed and treated at a Samsung Medical Center between 1994 and 2016. We reviewed primary tumor size, number and location of LNM, and presence of distant metastases to reveal relationships between tumor burden and extent and preoperative serum thyroglobulin levels. We found a linear association between increasing preoperative thyroglobulin levels, the size of the primary tumor, and the number of LNM (r = 0.34, p < 0.001, r = 0.20, p < 0.001, respectively). Tumor extent also increased with each decile of increasing preoperative thyroglobulin level (r = 0.18, p < 0.001). Preoperative thyroglobulin levels of 13.15 ng/mL, 30.05 ng/mL, and 62.9 ng/mL were associated with the presence of ipsilateral lateral LNM, contralateral lateral LNM, and distant metastasis, respectively. Our results suggest that preoperative measurement of serum thyroglobulin may help to predict LNM and help to tailor surgery.

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Radioiodine-Refractory Thyroid Cancer: Molecular Basis of Redifferentiation Therapies, Management, and Novel Therapies

Cancers ◽

10.3390/cancers11091382 ◽

2019 ◽

Vol 11 (9) ◽

pp. 1382 ◽

Cited By ~ 7

Author(s):

Mohamed Aashiq ◽

Deborah A. Silverman ◽

Shorook Na’ara ◽

Hideaki Takahashi ◽

Moran Amit

Keyword(s):

Thyroid Cancer ◽

Protein Kinase ◽

Tyrosine Kinase ◽

Mitogen Activated Protein Kinase ◽

Sodium Iodide Symporter ◽

Tumor Resistance ◽

Loss Of Function ◽

Iodide Uptake ◽

Mitogen Activated Protein ◽

Recurrent Thyroid Cancer

Recurrent, metastatic disease represents the most frequent cause of death for patients with thyroid cancer, and radioactive iodine (RAI) remains a mainstay of therapy for these patients. Unfortunately, many thyroid cancer patients have tumors that no longer trap iodine, and hence are refractory to RAI, heralding a poor prognosis. RAI-refractory (RAI-R) cancer cells result from the loss of thyroid differentiation features, such as iodide uptake and organification. This loss of differentiation features correlates with the degree of mitogen-activated protein kinase (MAPK) activation, which is higher in tumors with BRAF (B-Raf proto-oncogene) mutations than in those with RTK (receptor tyrosine kinase) or RAS (rat sarcoma) mutations. Hence, inhibition of the mitogen-activated protein kinase kinase-1 and -2 (MEK-1 and -2) downstream of RAF (rapidly accelerated fibrosarcoma) could sensitize RAI refractivity in thyroid cancer. However, a significant hurdle is the development of secondary tumor resistance (escape mechanisms) to these drugs through upregulation of tyrosine kinase receptors or another alternative signaling pathway. The sodium iodide symporter (NIS) is a plasma membrane glycoprotein, a member of solute carrier family 5A (SLC5A5), located on the basolateral surfaces of the thyroid follicular epithelial cells, which mediates active iodide transport into thyroid follicular cells. The mechanisms responsible for NIS loss of function in RAI-R thyroid cancer remains unclear. In a study of patients with recurrent thyroid cancer, expression levels of specific ribosomal machinery—namely PIGU (phosphatidylinositol glycan anchor biosynthesis class U), a subunit of the GPI (glycosylphosphatidylinositol transamidase complex—correlated with RAI avidity in radioiodine scanning, NIS levels, and biochemical response to RAI treatment. Here, we review the proposed mechanisms for RAI refractivity and the management of RAI-refractive metastatic, recurrent thyroid cancer. We also describe novel targeted systemic agents that are in use or under investigation for RAI-refractory disease, their mechanisms of action, and their adverse events.

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