Metastatic Thyroid Research Articles

SUN-LB100 False Elevation of Thyroglobulin by Immunoassay with Negative Thyroglobulin Antibody and Measures Blocking Heterophile Antibody in a Patient Post-thyroidectomy for Papillary Thyroid Cancer; Use of Liquid Chromatography─Tandem Mass Spectrometry

Background: Thyroglobulin (Tg) is a useful tool to monitor residual or recurrent differentiated thyroid cancer in patient post-thyroidectomy. The test is typically performed using immunoassay, which is subject to interference by thyroglobulin antibody (TgAb) and heterophile antibody (HAb). TgAb is routinely checked to validate the test result. Pre-treatment of specimen with HAb blocking agents is adopted to prevent interference by HAb. Clinical Case: A 71-year male had incidental thyroid nodules, leading to discovery of papillary thyroid cancer status post thyroidectomy. There were two sub-centimeter cancer foci, partially encapsulated without capsular or vascular invasion, and surgical margin was clear. It was classified as pT1aNxMx, without clinical evidence of lymph node or distant metastasis. Thyroid remnant ablation was not planned. Measurements of Tg (ng/mL)/TgAb (+ or -) before and after surgery were: Pre-surgery 48.7/ (-); 3M post-surgery 1.7/ (-); 6M post-surgery 450.3/ (-). Tg levels remained markedly elevated up to > 1000 ng/mL with negative TgAb upon repeats and follow-ups. The high Tg levels prompted search for thyroid tissue, either normal or cancerous. Thyroid/Neck thyroid ultrasound didn’t reveal suspicious lesion. Radioactive iodine (RAI) whole body scan showed two foci at thyroid bed, without evidence of ectopic thyroid, node or distant metastasis. The patient received 74.3 mCi I-131 treatment. After RAI treatment, Tg levels remained markedly elevated, ranging from 434.6 to 1232.1 ng/mL, all with negative TgAb. The discrepancy of clinical observations and Tg results suggested false readings of Tg assays. As TgAb had been consistently negative, assay interference by HAb was strongly suspected, but specimen pre-treated with HAb blocking agents yielded similar results. Tg measurement by liquid chromatography─tandem mass spectrometry was performed, and Tg was undetectable, < 0.5 ng/mL, confirming the clinical impression that elevated Tg levels by immunoassay were false regardless negative TgAb and pre-treatment of specimen with HAb blocking agents. Conclusion: Elevated Tg levels by immunoassay can be false even with negative TgAb and pre-treatment of specimen with HAb blocking agents. When Tg levels are inconsistent with clinical findings, Tg measurement by liquid chromatography─tandem mass spectrometry is useful to uncover the false readings before proceeding to extensive work-up and treatment. Reference: (1) Preissner, C., O’Kane, D., Singh, R., Morris, J., Grebe, S. Phantoms in the assay tube: Heterophile antibody interferences in serum thyroglobulin assays. J Clin Endocrinol Metab 2003;88:3069-74 (2) Netzel, B., Grebe, S., Algeciras-Schimnich, A. Usefulness of a thyroglobulin liquid chromatography─tandem mass spectrometry assay for evaluation of suspected heterophile interference. Clin Chem 2014;60:1016-8 Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

SUN-615 Hurdles in Hurthle Cell Cancer: A Case Report on Hurthle Cell Thyroid Cancer with Vertebral Metastasis

Introduction: Hurthle cell thyroid carcinoma (HCC) is a rare variant of follicular thyroid cancer, exhibiting a different clinical behavior and believed to be more aggressive but with relatively good prognosis. Correct identification of HCC in indeterminate cytological samples is challenging and ultrasound features can be misleading. No specific recommendations exist, making the management of HCC difficult [1]. Clinical Case: A 55-year-old obese woman with history of hypertension and stroke presented with severe back pain, and progressive lower leg motor and sensory weakness over 4 months. Two months prior to consult, a T7 vertebral mass was discovered, and she subsequently underwent decompressive surgery. Histopathology revealed metastatic follicular variant or papillary thyroid carcinoma. The patient was in severe pain and had complete loss of motor and sensory function in lower extremities. Thyroid exam revealed palpable nodules. Neck UTZ showed well-defined calcified nodules in both thyroid lobes, with largest in the mid-section of right lobe measuring 3.3 x 1.6 x 1.9 cm with minimal peripheral vascularity. She was given oxycodone, pregabalin, paracetamol and IV dexamethasone. Palliative radiotherapy was given using external-beam radiotherapy targeting T7 at a dose of 30 Gy in 10 fractions/ 10 days. Urinary tract infection, hypertension and constipation were detected and managed accordingly. She underwent total thyroidectomy 20 days later. Histopathology showed minimally invasive HCC with 4 cm tumor, no extrathyroidal extension, and negative for lymph node involvement. Post-surgical radiotherapy at 150 mCi I-131 was given. Post-ablation whole body scan revealed single island at right thyroid bed with an intense localization to the left of spinal column at the level of T6-T7, suggestive of functioning thyroid metastasis. TSH suppression was initiated. There is significant improvement within 3 months. She regained bladder and bowel control, as well as improvement in motor and sensory strength. Currently there is continuous improvement in function. Conclusion: Early recognition and prompt management should be done to all patients with HCC. UTZ and FNAB suggestive of Hurthle cell morphology can guide us in detecting HCC.

SAT-586 Primary Fallopian Tube Carcinoma Metastasizing to the Thyroid Gland: A Rare Cause of Hypothyroidism

Background: Primary fallopian tube carcinoma (PFTC) has been considered to account for only about 0.1-0.5% of all gynecologic cancers. It is notorious for metastasis to the ovaries, omentum, and uterus but has never been reported to present with hypothyroidism as a metastatic thyroid nodule. Case: A 53-year-old female presented with fatigue, generalized weakness and constipation for the last 4 months. Her past medical history was significant for stage IV poorly differentiated PFTC status post total abdominal hysterectomy, omentectomy and tumor debulking due to the local spread of the PFTC. She also underwent multiple cycles of chemotherapy with paclitaxel, cisplatin, doxorubicin and bevacizumab and was declared in remission by her oncologist. On examination, her vital signs were stable. Thyroid examination showed palpable nodules in the right and left lobes. Her laboratory investigation revealed normal liver and renal function tests, but the blood chemistry was significant for raised TSH levels of 68.8 mcIU/ml and decreased T3 and T4 levels of 45 ng/dL and 0.54 ng/dL respectively. Thyroid Peroxidase Antibody level was less than 3 IU/ml (reference range <6 IU/ML). Thyroid ultrasound showed a 2.3 x 0.7 x 2 cm solid nodule in the medial lower pole of the right lobe with and a 1.9 x 0.8 x 1.1 cm solid nodule in the medial lower pole of left lobe with increased vascularity. The fine needle aspiration cytology revealed groups of highly atypical cells showing enlarged, irregular, crowded nuclei which were intermixed with scattered bland follicular cells and macrophages. These atypical cells were identical to the serous carcinoma cells seen on previous PFTC specimens, confirming the hematogenous spread of PFTC to the thyroid gland. This diagnosis was further substantiated by immunohistochemical staining, which showed two different populations of cells, thyroid cells stained positive for TTF-1 (Thyroid transcription factor-1) while other cells were positive for WT-1 immunohistochemical stain strongly suggestive of metastatic serous carcinoma. Her serum cancer antigen 125 (CA 125) was also found to be elevated at 395 U/ml (normal range 0-35 U/ML) suggesting recurrence of PFTC. Niraparib chemotherapy was initiated. She was also started on 75 mcg of Levothyroxine per day. TSH levels after two months were 4.2 mcIU/ml. Conclusion: PFTC can be diagnosed early in its course using transvaginal Doppler ultrasound to detect areas of neovascularization within the fallopian tube. PFTC has histological and clinical resemblance with ovarian and uterine primaries and hence can be challenging to diagnose. It is incredibly uncommon to suspect thyroid metastasis from the residuals of PFTC as a possible etiology of hypothyroidism. Thus, physicians should keep a very high index of suspicion in appropriate clinical settings. Prognosis remains poor as most patients present with metastatic disease.

Study on the mechanism of interleukine-11 promoting anaplastic thyroid carcinoma cells invasion and metastasis

Objective To explore the mechanism of hypoxia inducing interleukine (IL)-11 secretion in anaplastic thyroid carcinoma (ATC) cells and the mechanism of IL-11 promoting epithelial mesenchymal transition of ATC cells. Methods Knockdown of IL-11, hypoxia-inducible factor (HIF)-1α in ATC cells or treatment of ATC cells with Cobalt Chloride, recombinant human interleukin (rhIL)-11, IL-11 antibody, then the effects of these interventions on the invasion and migration ability of ATC cells and its mechanism were detected by enzyme-linked immunosorbent assay (ELISA), Transwell, Real-time polymerase chain reaction (PCR), Western blotting. Results Under treatment with Cobalt Chloride, the protein and mRNA expression of IL-11 increased in ATC cells. The number of invasive cells in the knockdown HIF-1α group (61.7±4.9, 30.0±4.6) was less than that of the control group 261.7±8.7 (P<0.01), and the number of migrated cells (87.3±4.5, 73.8±5.4) was less than the control group 337.3±7.1 (P<0.01). The expression ofphosphorylated Akt (p-Akt), phosphorylated glycogen synthase kinase 3β (p-GSK3β) and Snail protein was significantly increased after treatment with rhIL-11. The protein expression of p-Akt, p-GSK3β and Snail were significantly decreased after knockdown of IL-11 expression in ATC cells. Conclusion Hypoxia induced epithelial mesenchymal transition of ATC cells is the main mechanism of high invasion and migration of ATC cells. Key words: Anaplastic thyroid carcinoma; Interleukine-11; Epithelialmesenchymal transition; Invasion and metastasis

MiR-630 inhibits papillary thyroid carcinoma cell growth, metastasis, and epithelial-mesenchymal transition by suppressing JAK2/STAT3 signaling pathway.

Evidence has demonstrated that miR-630 is involved in multiple processes in cancer development and progression. However, the exact functions of miR-630 in papillary thyroid carcinoma (PTC) and the underlying mechanisms remain undefined. Therefore, the aims of the present study were to investigate the role and potential mechanism of miR-630 in tumorigenicity of PTC. Microarrays were used to analyze the differentially expressed miRNAs in PTC tissues. Expression of miR-630 in PTC tissues and cell lines were determined by a qRT-PCR assay. CCK-8 assays, clonogenic survival assays, cell apoptosis analysis, wound healing assays and transwell invasion assays were used to examine the tumorigenesis function of miR-630 in vitro. Protein expression of signaling pathways was determined by using Western blot. We found that miR-630 was significantly downregulated in PTC tissues and cell lines. Overexpression of miR-630 inhibited PTC cell proliferation and induced cell apoptosis via suppressing the expression of caspase-3 and caspase-6. In addition, up-regulation of miR-630 suppressed the migration and invasion in PTC cells by suppressing EMT progress. Mechanistic investigations showed forced miR-660 expression decreased proteins expression of phosphorylation levels in JAK2/STAT3 signaling. We firstly provided the evidence that miR-630 displayed a tumor-promotive role in PTC progression through modulating JAK2/STAT3 pathway, and that a potential therapeutic strategy through enhancing miR-630 expression might benefit PTC patients.

Impact of tumor-associated macrophages and BRAFV600E mutation on clinical outcomes in patients with various thyroid cancers.

Tumor-associated macrophages (TAMs) play a role in thyroid cancer tumor progression and metastasis. This study aimed to investigate the association of TAM density and cluster of differentiation 68 (CD68) expression with thyroid tumors as a prognostic marker and the relationship of these factors with BRAFV600E mutations. This study included 275 thyroid specimen tissues, including benign and malignant lesions. We compared the clinicopathological features according to thyroid tumor types and evaluated the presence of CD68 expression and BRAFV600E mutations. CD68 positive expression increased with aggressiveness of thyroid tumor histologic grades (P < 0.001). In patients with poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC), CD68 positivity was associated with aggressive adverse clinical outcomes such as extrathyroidal extension, cervical lymph node metastases, and distant metastases (P < 0.05). CD68 positivity was more frequent in advanced and aggressive thyroid cancer types such as PDTC/ATC.

The relationship between positron emission tomography-computed tomography imaging and histopathological features of thyroid incidentalomas detected during follow-up for primary malignancy.

While the rate of thyroid incidentaloma detected on positron emission tomography (PET) was reported as 4%, the malignancy rate was 14%-50%. We evaluated the thyroid nodules which were detected by PET-computerized tomography (CT) in cancer patients and analyzed the pathological results of those thyroid nodules diagnosed by fine needle aspiration biopsy (FNAB) and their correlation with the maximum standardized uptake (SUVmax) value and PET imaging features. FNAB were performed for 40 thyroid incidentalomas. We analyzed the relationship between the histopathological findings and radiological features by Pearson's correlations and Chi-square-Fisher's exact tests to evaluate the factors associated with SUVmax. The median SUVmax values were 5.4 for thyroid nodules. Totally, 14 malignancies were detected by FNAB (35%).The sensitivity and specificity of SUVmax value for diagnosis of malignancy were 87.5% and 52%, respectively. Positive and negative predictive values were 36.8% and 92.8%. The most common malignant and benign pathologies were classic variant papillary carcinoma and benign colloidal nodule. The median SUVmax was the higher in colon cancer thyroid metastasis and oncocytic neoplasia (SUVmax 14.5 and 13.6, respectively). Histopathological type was not related with nodule size but positively associated with categorical SUVmax(r = 0.318, P = 0.04) and negatively correlated with both the density of the thyroid nodule in PET-CT (r = -0.0042, P = 0.01) and density of nodule in ultrasound (USG) (r = -0.305, P = 0.05). Margin of the thyroid nodule in USG (P = 0.007) and internal component of the nodule in PET (P = 0.03) were found to be important factors to differentiate benign or malignant lesion. If the thyroid nodule is detected with flouro-2-deoxy-D-glucose uptake, to differentiate benign nodule from malignant, cytological examination is noteworthy to diagnose the more aggressive type of thyroid nodule and also thyroid metastasis from primary cancer.

Clinical implications of Delphian lymph node metastasis in papillary thyroid carcinoma: a single-institution study, systemic review and meta-analysis

BackgroundTo evaluate the possible predictive value and clinicopathological characteristics of Delphian lymph node metastasis in papillary thyroid carcinoma.MethodsA retrospective analysis of papillary thyroid carcinoma patients with Delphian lymph node metastasis in a single institution and meta-analysis of literature reports were performed.ResultsIn own series, Delphian lymph node metastasis was detected in 19 (9.9%) of 192 papillary thyroid carcinoma patients and was significantly associated with tumor size≥1 cm (P = 0.003), multifocality (P = 0.006) and extrathyroid extension (P < 0.001) in the multivariate analysis. Female was a protective factor for Delphian lymph node metastasis (P = 0.001). Delphian lymph node metastasis was highly predictive of further central lymph node metastasis (positive predictive value = 89.5%, negative predictive value = 67.6%) and moderately predictive of lateral lymph node metastasis (positive predictive value = 26.3%, negative predictive value = 95.4%). In this meta-analysis, there was a strong correlation between Delphian lymph node metastasis and aggressive clinicopathologic characteristics with regards to multifocality (P = 0.0008), bilaterality (P = 0.04), extrathyroid extension (P < 0.00001), lymphovascular invasion (P < 0.00001), further central lymph node metastasis (P < 0.00001) and lateral lymph node metastasis (P < 0.00001).ConclusionsThis single-institution observational study and meta-analysis identified that Delphian lymph node metastasis was significantly associated with unfavorable clinicopathological characteristics and had a strong predictive power for further disease in the central compartment.Trial registrationThe clinical study was retrospectively registered to UMIN clinical trials registry (the registry number: UMIN000033835).

Targeted inhibition of long non-coding RNA H19 blocks anaplastic thyroid carcinoma growth and metastasis

ABSTRACT Long non-coding RNA H19 (H19) is highly expressed in cancers and is considered to highly correlate with the extent of malignant degree. The present study was performed to determine the expression levels of H19 in anaplastic thyroid carcinoma (ATC) tissues and the role of H19 in ATC 8505C cells in vitro and in vivo. Expression of H19 was detected in 19 ATC and 19 normal thyroid tissues by real-time quantitative polymerase chain reaction. Utilizing the siRNA or short hairpin RNA (shRNA) directed against human H19 (H19 siRNA or shRNA H19) depleted H19 in ATC 8505C cells and characterized the outcomes. The results showed that H19 was overexpressed in ATC tissues. Targeting H19 inhibited proliferation, migration, and invasion and induced apoptosis in 8505C cells in vitro and inhibited tumorigenesis and metastasis in vivo. Therefore, the H19 might be an effective target for ATC molecular therapy.

Thyroid hormone, PD-L1, and cancer

Objective: Thyroid hormone plays a vital role in maintaining whole-body physiological activities. However, several different disorders can arise when thyroid hormone is abnormal. Even more, thyroid hormone has been shown to stimulate cancer cell proliferation at physiological concentration. By binding to cell surface integrin αvβ3, thyroid hormone, especially thyroxine activates ERK1/2 activation and sequentially stimulates cell proliferation. Different mechanisms have been demonstrated to be involved in thyroxine-induced cancer proliferation. Checkpoint, PD-1/PD-L1, has shown highly correlated to cancer proliferation and survival. Data Sources: We examined actions of thyroxine and Nano-diamino-tetrac (NDAT; Nanotetrac) on PD-L1 mRNA abundance (qPCR) and PD-L1 protein content in various cancer cells. Methodologies used are qPCR, Western blot analyses, confocal microscopy, and xenograft. Study Selection: We investigate mechanisms involved in thyroid hormone-induced PD-L1 expression and inhibitory effect of NDAT on thyroid hormone-induced PD-L1 expression. Either blocking thyroid hormone-binding on integrin αvβ3 or using NDAT can inhibit PD-L1 expression. Results: Our studies indicate that thyroid hormone induces PD-L1 expression via activating ERK1/2, PI3K, and STAT3 in different types of cancer cells. NDAT inhibits the cancer cell PI3-K and MAPK signal transduction pathways that are critical to PD-L1 gene expression. Other studies on PubMed also indicate thyroxine's actions are via integrin αvβ3. Conclusions: Thyroid hormone-induced PD-L1 expression not only facilitates cancer cell proliferation but also interferes with chemotherapy. In this current review, we will discuss mechanisms involved in thyroid hormone-induced PD-L1 expression. In addition, role of PD-L1 in thyroid hormone-induced cancer growth and metastasis will be addressed.

Genistein inhibits human papillary thyroid cancer cell detachment, invasion and metastasis.

Papillary thyroid carcinoma (PTC) is the most commonly diagnosed endocrine cancer, and those with BRAFV600E mutation have high recurrence rate and less favorable clinical behavior. Genistein having anti-carcinoma effects in various types of carcinomas as an estrogen analog, but the mechanism of Genistein in the progression of PTC remains unknown. Genistein significantly inhibits the proliferation and the invasion (P < 0.01), and the apoptosis (P < 0.001) of all tumor cell lines, which was probably due to the inducing of the arrest in G2/M phase of the cell cycle (P < 0.001). The anti-proliferation and apoptosis inducing effects are more obvious in BCPAP, IHH4 cell lines harboring BRAFV600E mutation. Genistein significantly decreased the invasion of PTC cell lines and partially reverses epithelial mesenchymal transition in PTC cell lines. Functional study indicated that small interfering RNA (siRNA) knockdown of β-catenin significantly reverses the effect of genistein on EMT at protein levels. In conclusion, for the first time, our study suggested that genistein has anticarcinoma effect for PTC patients in the range of 2.5 and 80 μg/ml in thyroid carcinoma cells, which was probably through cytoplasmic translocation of β-catenin. Further study will be needed to determine whether genistein could be used in clinical trial of high-risk PTC.

57 Study of the camera’s limit of detectability with Iodine-131

Introduction In differentiated thyroid cancer, scintigraphic images are performed after therapeutic administration of iodine-131. Several courses are proposed in case of thyroid markers arise due to thyroid’s cell regrowth or metastatic disease appearance. As disease evolves, in some cases, thyroid cells no longer absorb iodine-131 and thus, remain unseen on scintigraphic images. This situation leads to the end of iodine-131 treatments for the patient. Nevertheless, lack of detection does not equally correspond to absence of thyroid tissues or metastasis. In this context, we have evaluated the limit of detectability of our gamma-camera. Methods Gate (v7) Monte-Carlo code was used to model our gamma-camera ( Discovery NM / CT 690, GEHC). Acquired and modelled spatial resolution, sensitivity and contrast (SR, S, C) were compared. Collimator Angular response function (ARF) was used to speed simulations up and get images of a cylindrical object in different geometrical conditions close to clinical settings (radioactive concentration, tumor’s volume and depth) used to conduct a Receiver Operating Characteristic (ROC) study with several physicians. We have also studied different models of automatic observers in order to get closest results as possible to human observer ROC study. Results Simulated and acquired images have identical SR, S and C characteristics. Simulations were 20 times faster with ARF table than without. ROC/LROC human study shows an important variability in detection performances. Some automatic observers such as “2–Alternative Forced Choice” method present close performances to human observers whereas others like CHO outperformed them. Those different results allow us to derive an empirical law, relating the minimal radioactive concentration to detect a lesion as function of its depth and size. Regardless of lesion depth, a radioactive concentration of 25 kBq/mL is necessary to detect all lesions superior to 15 mm. Conclusions We performed a ROC/LROC study on simulated images to evaluate our camera detectability limit and we confirmed that lesions might stay unseen on scintigraphic images as long as radioactive concentration is below some threshold.

Massive thyroid gland metastasis from non small cell lung cancer

Massive thyroid gland metastasis from non small cell lung cancer

Solitary thyroid metastasis from a high grade serous ovarian epithelial carcinoma

Solitary thyroid metastasis from a high grade serous ovarian epithelial carcinoma

ID Proteins May Reduce Aggressiveness of Thyroid Tumors.

ID genes have an important function in the cell cycle, and ID proteins may help identify aggressive tumors, besides being considered promising therapeutic targets. However, their role in thyroid tumors is still poorly understood. We examined ID expression and their correlation with diagnostic and prognostic features aiming to find a clinical application in differentiated thyroid carcinoma (DTC) cases. mRNA levels of ID1, ID2, ID3, and ID4 genes were quantified and their expression was observed by immunohistochemistry in 194 thyroid samples including 68 goiters, 16 follicular adenomas, 75 classic papillary thyroid carcinomas, 18 follicular variants of papillary thyroid carcinoma, 5 follicular thyroid carcinomas, and 1 anaplastic thyroid cancer, besides 11 normal thyroid tissues. DTC patients were managed according to standard protocols and followed up for M = 28 ± 16months. ID2, ID3, and ID4 mRNA levels were higher in benign (2.0 ± 1.9; 0.6 ± 0.6; and 0.7 ± 1.0AU, respectively) than those in malignant nodules (0.30 ± 0.62; 0.3 ± 0.3; and 0.2 ± 0.3AU, respectively, p< 0.0001 for all three genes) and were associated with no extra thyroid invasion or metastasis at diagnosis. ID3 nuclear protein expression was higher in benign than that in malignant cells (5.2 ± 0.9 vs 3.0 ± 1.8AU; p< 0.0001). On the contrary, the cytoplasmic expression of ID3 was higher in malignant than that in benign lesions (5.7 ± 1.5 vs 4.0 ± 1.4AU; p< 0.0001). Our data indicate that ID genes are involved in thyroid tumorigenesis and suggest these genes act impeding the evolution of more aggressive phenotypes. The different patterns of their tissue expression may help identify malignancy and characterize thyroid lesion aggressiveness.

Metastatic clear cell renal cell carcinoma to the thyroid gland: A clinico-pathological and immunohistochemical study of 8 cases and review of the literature

When a patient with a previous history of neoplasm presents with a thyroid lesion, the possibility of it being metastatic should always be considered.In this series, we present the clinicopathological and immunohistochemical features of the thyroid metastases diagnosed in our department over the past 30 years.Here we present eight thyroidal metastases from clear cell renal cell carcinoma (ccRCCC), including a tumor to tumor metastasis, the patients being 2 men and 6 women with a median age of 62 years. The majority had a past history of goiter and a single and palpable metastasis. In one patient the thyroid metastases were the first sign of the ccRCCC. In the available cases, the metastasis showed positivity to PAX8 and CAIX and negativity to TTF1 and thyroglobulin.The median time from the detection of the primary renal tumor to thyroid metastasis and from thyroidectomy to last follow up were 84.17 and 54.50 months, respectively. After a median follow up of 158.50 months none of the patients had died from ccRCCC.Renal cell carcinoma (RCC) is the most frequent malignant neoplasm of the kidney and its incidence has increased over recent decades. In a clinical series, up to 1–3% of the oncologic thyroidectomies were due to thyroid metastases and the most frequent metastasizing tumor was RCC, followed by lung and breast cancer.

Effects of thyrotropin suppression on lumbar bone mineral density in postmenopausal women with differentiated thyroid carcinoma.

PurposeThe aim of this study was to evaluate the effect of postoperative thyroid-stimulating hormone suppression (TSHS) on bone mineral density (BMD) in Chinese postmenopausal women with differentiated thyroid carcinoma (DTC).Patients and methodsA total of 225 postmenopausal women with DTC who had received TSHS were included in the study. Postmenopausal women with postoperative DTC undergoing thyroid residual ablation or metastasis treatment between 2009 and 2015 were enrolled and followed up for 2 years. They were divided into two groups: TSHS group (median thyroid-stimulating hormone [TSH] <0.3 μIU/mL) and postmenopausal control group (median TSH >0.3 μIU/mL). Lumbar 1–4 BMD levels were measured by a dual-energy X-ray absorptiometry (DXA) at baseline and 6, 12 and 24 months. All patients had calcium and vitamin D supplementation. The diagnosis of osteopenia (−1 SD > T >−2.5 SD) and osteoporosis (T <−2.5 SD) was made according to WHO guidelines.ResultsThyroid cancers included 211 papillary carcinomas and 14 follicular carcinomas. One hundred and fifty-four patients were in the TSHS group, and 71 patients were in the non-suppressed TSH group (postmenopausal controls). No significant differences were found in the BMD of the lumbar spine between baseline and after 6, 12 and 24 months, pre and post treatment in TSHS and non-suppressed TSH patients. Compared with pre-TSHS, there was a reduction in the BMD of 1.9% in the lumbar spine at the 2-year follow-up. Significant difference in the number of osteopenia and osteoporosis patients at 24 months (χ2=2.88, P=0.004) was found between the TSHS (103/152) and postmenopausal control (32/68) groups. TSHS is not a significant risk of bone loss, but it is the incidence of osteopenia in postmenopausal women with DTC.ConclusionOur 2-year follow-up data indicated that TSHS had little effect on BMD in postmenopausal women with DTC. Large population with at least 5-year follow-up should be further investigated. BMD in postmenopausal women with DTC should be followed up regularly.

MiR-214 regulates papillary thyroid carcinoma cellproliferation and metastasis by targeting PSMD10.

MicroRNAs (miRNAs) have important effects on cancer occurrence and development by adjusting gene expression. The aim of the present study was to examine the role of miR-214 in papillary thyroid carcinoma cell proliferation and metastasis, and its molecular mechanisms. miR-214 was demonstrated to be markedly downregulated in papillary thyroid carcinoma tissues and cells compared with normal, and this was significantly associated with lymph node metastasis, tumor size and TNM stage. Upregulation of miR-214 significantly decreased cell proliferation, and promoted cell apoptosis and cell cycle arrest in papillary thyroid carcinoma cell lines in vitro. By contrast, downregulation of miR-214 resulted in the opposite effects. In addition, miR-214 mimics significantly decreased papillary thyroid carcinoma cell migration and invasion, which was correlated with decreased expression levels of matrix metallopeptidase (MMP)-2 and MMP-9. Restoration of miR-214 expression in papillary thyroid carcinoma cells decreased the activities associated with epithelial-mesenchymal transition (EMT). Furthermore, proteasome 26S subunit non-ATPase 10 (PSMD10) was predicted to be a target of miR-214. Experimental results demonstrated that miR-214 negatively regulated PSMD10 expression by targeting its 3′ untranslated region directly. Knockdown of PSMD10 reduced papillary thyroid carcinoma cell clone formation, migration and invasion, most likely by repressing glycogen synthase kinase (GSK)-3β/β-catenin and AKT signaling. Finally, a negative correlation was observed between the expression levels of miR-214 and PSMD10 in papillary thyroid carcinoma tissues. Taken together, these data suggested that miR-214 might be a candidate target for the treatment of papillary thyroid carcinoma.

Clinical observation of metastatic thyroid disease in a patient with breast cancer

Metastatic tumors of the thyroid gland (TG) are rare. Usually thyroid gland metastases originate from renal, lung, skin and gastrointestinal cancers. Breast cancer metastases are more rare and in various samples amount to 3 to 34% of all cases of the metastatic thyroid disease. We present a rare case of metastatic carcinomatosis into the thyroid goiter in a 63-year old female patient who has received combination therapy for breast cancer. In 2016, right-sided mastectomy was performed due to the right breast cancer (invasive carcinoma, non-specific type, Grade 2, with skin invasion) with subsequent four chemotherapy courses. A slowly growing nodule in the thyroid gland was first found in 2012; in 2017, fine needle aspiration biopsy was performed, which showed a follicular tumor that resulted in thyroidectomy. At the histological examination, against the background of thyroid goiter, multiple small lesions with advanced nuclear polymorphism were found, with doubtful diagnosis. To clarify the histogenesis of the tumor lesions, immunohistochemical assessment was performed. Its first phase included the markers of primary thyroid tumors (thyroglobulin, TTF-1), and the second one consisted of the breast cancer diagnostic panel (mammoglobin, GATA-3, estrogen and progesterone receptors). The results showed multiple small metastases of the invasive breast carcinoma of non-specific type into the thyroid goiter. Taking into account eventual problems of differential diagnosis and significant morphological polymorphism of thyroid tumors, we recommend extending of the immunohistochemistry panel in this patient category.

TEKT4 Promotes Papillary Thyroid Cancer Cell Proliferation, Colony Formation, and Metastasis through Activating PI3K/Akt Pathway.

Thyroid carcinoma is the most common malignancy of the endocrine system worldwide, but its molecular mechanisms remain unclear. Some diseases are associated with TEKT4 gene. However, its role in thyroid carcinoma has yet to be fully examined. This study was designed to investigate the function of TEKT4 in papillary thyroid cancer (PTC). The effect of TEKT4 on aggressive behavior of PTC cell lines, namely, TPC1 and BCPAP, transfected with small interfering RNA was identified through cell proliferation, colony formation, migration, and invasion. Our previous study revealed that TEKT4 may be vital in PTC. In in vitro experiments, TEKT4 downregulation suppressed cell proliferation, colony formation, cell migration, and invasion. Our data also indicated that tumor-suppressing role of TEKT4 knockdown in PTC cell lines was associated with the silence of the PI3K/Akt pathway. Our study revealed that TEKT4 shows important biological implications and is worthy of further study.