Differentiated Thyroid Tumors Research Articles

Detection of driver mutations in plasma cell-free nucleic acids in differentiated thyroid neoplasm.

This proof-of-concept paper demonstrates that driver mutations can be detected in plasma in differentiated thyroid tumors, and we were able to detect mutations in upto 80% malignant thyroid nodules. Additionally, cancer subtypes could also be predicted using a 8-gene panel. In almost 90% follicular adenoma, rat sarcoma virus (RAS) mutations were detectable. There was a strong agreement between driver mutations found in plasma samples, FNAC materials, and histopathology samples. This has potential as a noninvasive, preoperative diagnostic tool (particularly of clinical importance in indeterminate nodules) and may help in detection of residual tumor after surgery. Future research is warranted to test the role of this tool to detect tumor recurrence. Ultrasonographic (USG) evaluation and fine-needle aspiration (FNA) are cornerstone for evaluation of thyroid neoplasm. Molecular technique including detection of driver mutation from FNA cytology (FNAC) material is an established modality. In this study, we explored the feasibility of using plasma cell-free nucleic acids to identify known driver mutations in differentiated thyroid neoplasm. Patients presenting with thyroid nodules underwent USG with Thyroid Image Reporting and Data Systems scoring and FNAC (Bethesda classification). All patients in Bethesda 3, 4, 5, 6 underwent surgery and histopathological confirmation. Patients in Bethesda 2 (cosmetic concerns, compressive symptoms) underwent surgery, and rest were presumed benign on the basis of USG, FNAC features, and clinical followup.). Endocrinology clinic. Subjects with thyroid nodule. None. Plasma sample, FNA, and histopathology material were evaluated for driver mutations (8-gene panel comprising BRAF-V600E, RET/PTC3, RET/PTC1, TERT promoter, HRAS, NRAS, KRAS, and PAX8-PPARG). A total of 223 subjects were recruited; of these 154 were benign and 69 had differentiated thyroid cancer. We were able to detect driver mutation from plasma in 55 subjects (79.71%) of all malignant patients, and 11 patients in benign category had RAS mutation (follicular adenoma). Rest of the benign nodules did not have any detectable driver mutations. Plasma might be a viable noninvasive alternative source for detection of driver mutations (8-gene panel) in subjects with differentiated thyroid tumors and may have significant clinical utility.

EVALUATION OF INFLAMMATION-RELATED HEMOGRAM PARAMETERS AS A USEFUL MARKER IN PAPILLARY THYROID CARCINOMA

Objective
 Inflammation-related hemogram parameters have
 recently started to be defined as a useful marker in
 cancer patients. In this study, we aimed to comparison
 of hemogram parameters in papillary thyroid cancer
 (PTC) patients, well differentiated thyroid tumor
 of uncertain malignant potential (WDT-UMP) and
 follicular adenoma (FA).
 Material and Method
 The 287 patients’ data were analyzed in study. Study
 subjects were divided into 5 different groups. 1st
 group: control, 2nd group: FA, 3rd group: WDT-UMP,
 4th group: non-metastatic PTC, 5th group: metastatic
 PTC. We evaluated the preoperative blood tests.
 Results
 The average age was 50 (37-59). The mean TSH
 value was 1.2 (0.5-2.2) μIU/mL. The mean size of the
 lesion detected in the total thyroidectomy material was
 1.7 (1.0-3.0) cm. White blood cells (WBC), neutrophils
 and lymphocytes were lower in 3rd group than 4th
 group (p

ODP489 Insular Thyroid Cancer: A Rare Case of Undifferentiated Thyroid Carcinoma

Abstract Introduction Insular thyroid cancer (ITC) is a rare form of thyroid cancer derived from follicular cells. ITC requires a histopathologic diagnosis and has an intermediate morphology between well differentiated thyroid cancers (follicular and papillary) and undifferentiated thyroid cancer (anaplastic). The rate of metastasis and mortality are higher compared with well-differentiated thyroid carcinomas. Case presentation A 74-year-old woman presented for a 1 year history of rapidly progressive neck mass associated with neck pain, limited neck motion, loss of appetite, weight loss, and dysphagia. Past medical history included hypertension, type 2 diabetes, dyslipidemia, and vitamin D deficiency. There was no history of neck radiation or family history of cancer. Physical examination revealed a 10×7 cm neck mass with cervical adenopathy. Vital signs were unremarkable. Laboratory studies showed TSH of 0.71 uIU/mL (0.270-4.200), free T4 of 0.57 ng/dL (0.93-1.70) and thyroglobulins of 213.616 ng/dL (1.6-59.9). Neck CT demonstrated a multilobulated mass in the left thyroid lobe measuring 12×5.2×5.6 cm with tracheal deviation, multiple nodules surrounding the carotids and bone metastasis. Fine needle aspiration showed a mixed pattern of thyroid follicles. An excisional biopsy showed nests and sheets of small uniform cells with scattered abortive follicles and mitosis consistent with ITC. There was no necrosis. The Ki67 index was 10-20%. On immunohistochemical analysis TTF1 and thyroglobulin were positive and P63, calcitonin, and PTH were negative. Tracheostomy and PEG tube placement were required due to mass obstructive effect. Radiation and steroids were initiated before starting lenvatinib. The patient was not a surgical candidate due to tumor extension to the carotids. She ultimately succumbed to the disease after a 45-day hospital course complicated by pneumonia. Discussion ITC is a rare type of thyroid tumor with a mortality rate of 12-75%. The diagnosis is based on histopathology, demonstrating solid nests (insulae) of small, uniform carcinoma cells, small follicles containing thyroglobulin, frequent necrotic foci and variable mitotic activity. The tumor cells in ITC are derived from poorly differentiated follicular cells expressing thyroglobulin. The immunostaining of thyroglobulin differentiates ITC from other poorly differentiated thyroid tumors. In this case the immunohistochemical analysis was positive for thyroglobulin and negative for calcitonin, which confirmed that the tumor cells were follicular in origin 1 . ITC behaves differently compared with other thyroid carcinomas, with more frequent metastasis and lower average 20-year post-diagnosis survival. Our patient had other characteristics that conferred a poor prognosis, including advanced age, high rate of mitosis, and multiple metastases. Although surgery and radioactive iodine are first line, this patient's tumor extension required alternative therapies. Radiotherapy and lenvatinib, a tyrosine kinase receptor inhibitor, were employed unsuccessfully. 1. Soza, J., et al. Insular Thyroid Cancer. Cancer, 3260-3267. Presentation: No date and time listed

Comparative BRAF V600E immunohistochemical expression in differentiated thyroid tumors with papillary features.

Differentiated thyroid tumors (DTC) are the most common indolent tumors associated with a good prognosis compared with other tumors. Its incidence during the last few decades has increased. DTC includes papillary carcinoma and follicular carcinoma. The BRAF is the most prevalent genetic mutation in thyroid carcinoma, occurring in more than 50% of papillary thyroid cancers (PTCs). The study aimed to evaluate BRAF expression in differentiated thyroid tumors with papillary-like nuclear features. Formalin-fixed paraffin-embedded blocks (FFPE) were collected from archival samples of patients in private histopathology labs in Al-Najaf city from 55 cases, which included 27 papillary thyroid carcinoma (PTC) cases, 10 cases of NIFTP, 13 FVPTC cases, 2 papillary microcarcinoma cases, and 3 NIFTP coexist with papillary microcarcinoma cases. All samples were stained using the immunohistochemistry method in the Middle Euphrates unit for cancer research at the University of Kufa/Faculty of Medicine. 15/55 (27.3%) of cases increased BRAF expression. The BRAF expression was statistically significant with tumor type (p=0.008). The higher expression was associated with 13 (48.15%) of PTC cases. However, the BRAF expression did not correlate with gender (p=0.2), tumor size (p=0.07), and tumor focality (p=0.09). BRAF V600E has prognostic value as it correlates with tumor progression.

Induction of Premalignant and Malignant Changes in Nude Mice by Human Tumors-Derived Cell-Free Filtrates

Carcinogenesis is a vast and heterogeneous, multi-step process driven by genetic and epigenetic operators leading to superimposed “tumor organs”. Based on our previous experiences of reproducing human donor’s histopathological hallmarks in healthy animals exposed to pathologic tissues homogenates, we examined the consequences of administering crude homogenates elaborated from invasive human tumors to nude mice. Subcutaneous administrations of increasing protein concentrations of breast carcinoma homogenates for 6 and 12 weeks, induced lungs atypical adenomatous hyperplasia, foci of lepidic and solid growth poorly-differentiated adenocarcinomas at the two time points. Non-atypical mucosal hyperplasia and adenomas were detected along the gastrointestinal tract. Another experiment addressed the impact of daily administrations (100 μg protein/mouse) of anaplastic sarcoma tissue homogenate for a month. This scheme triggered proliferative changes including: lung adenocarcinomas; a subcutaneous, poorly-differentiated mesenchymal cells tumor, a lymphoadenoma, and multiple gastrointestinal adenomas. When 50% of the month-treated animals were left to evolve treatment-free for other 35 days, a larger and broader incidence of neoplastic changes was found, suggesting autonomous growth: lung adenocarcinomas, a poorly differentiated thyroid tumor, an epithelial tumor within the periaortic brown adipose tissue, and multiple adenomas. These findings indicate that tumor crude homogenates contains soluble “transforming” messengers, that in a short period of time disrupt tissues’ proliferative and differentiation programs drifting to progressive neoplasms. This study expands previous evidences on the ability of human pathologic tissues-derived homogenates, to induce the reproduction of diseased donor’s histopathologic hallmarks.

Mechanisms of regulating NIS transport to the cell membrane and redifferentiation therapy in thyroid cancer.

Iodine is an essential constituent of thyroid hormone. Active iodide accumulation in the thyroid is mediated by the sodium iodide symporter (NIS), comprising the first step in thyroid hormone biosynthesis, which relies on the functional expression of NIS on the cell membrane. The retention of NIS expressed in differentiated thyroid cancer (DTC) cells allows further treatment with post-operative radioactive iodine (RAI) therapy. However, compared with normal thyroid tissue, differentiated thyroid tumors usually show a decrease in the active iodide conveyance and NIS is generally retained within the cells, indicating that posttranslational protein transfer to the plasma membrane is abnormal. In recent years, through in vitro studies and studies of patients with DTC, various methods have been tested to increase the transport rate of NIS to the cell membrane and increase the absorption of iodine. An in-depth understanding of the mechanism of NIS transport to the plasma membrane could lead to improvements in RAI therapy. Therefore, in this review, we discuss the current knowledge concerning the post-translational mechanisms that regulate NIS transport to the cell membrane and the current status of redifferentiation therapy for patients with RAI-refractory (RAIR)-DTC.

The Difficulty of Post-Operative Surveillance of Calcitonin Negative Medullary Thyroid Cancer

Background: As a differentiated thyroid tumor, medullary thyroid cancer (MTC) typically maintains the secretory function of the c-cells with resultant increase in serum calcitonin level along with frequent elevations in serum chromogranin A (CgA) and carcinoembryonic antigen (CEA). Clinical Presentation: A 71-year-old female with history of multinodular goiter underwent a thyroid nodule biopsy after routine ultrasound surveillance revealed enlargement of two right lower lobe nodules compared with prior imaging. Fine needle aspiration (FNA) of one 3.1 x 1.9 x 2.7 cm right thyroid nodule revealed cellular material composed of spindle-shaped neoplastic cells, some of them with marked cytologic atypia, suspicious for a neuroendocrine tumor, specifically medullary thyroid carcinoma. A PET/CT scan was performed after injection of Gallium-68 dotatate radiotracer and revealed intense focal radiotracer activity in the approximately 2.5 x 2.1 cm right thyroid mid lower pole heterogeneous hypodense mass with tiny calcification inferiorly, consistent with the patient’s known tumor. There was no evidence of cervical octreotate avid metastatic lymphadenopathy and a chest x-ray showed no evidence of active pulmonary disease. The patient subsequently underwent a right partial thyroidectomy with isthmusectomy. Histopathology revealed a 2.8 x 1.9 x 1.9 cm neoplasm composed of spindle and polygonal cells growing in solid nests with neuroendocrine-type nuclei. Immunostains showed the tumor to be positive for AE1-AE3 cytokeratins, chromogranin, synaptophysin and CEA. It was focally positive for TTF-1 and calcitonin. Thyroglobulin and PAX-8 were negative. Using the AJCC 8th edition staging system, the tumor was staged a pT2Nx with margins uninvolved by carcinoma and no extrathyroidal extension or lymphatic invasion. Angioinvasion was present. Additional serum studies included a normal calcitonin value of <2.0 pg/ml (reference range 0-5.1 pg/ml), CEA 2.6 ng/ml (reference range <6.0 ng/ml), and a mildly elevated chromagranin A at 133 ng/ml (reference range 0-95 ng/ml). Plasma metanephrines, normetanephrines, vasoactive peptide, and glucagon levels were all unremarkable. Our patient’s surgical recovery was normal and two months later she remained asymptomatic without evidence of recurrence or metastasis. Discussion: The diagnosis and post-operative surveillance of medullary thyroid cancer is challenging; even more complicated is the rare case of calcitonin-negative MTC. The cause of calcitonin-negative MTC remains unclear. Further studies are needed for the discovery and development of novel biomarkers for post-operative surveillance and evaluation of clinical relapse.

Intratumoral Heterogeneity in Differentiated Thyroid Tumors: An Intriguing Reappraisal in the Era of Personalized Medicine.

Differentiated thyroid tumors (DTTs) are characterized by significant molecular variability in both spatial and temporal intra-tumoral heterogeneity (ITH), that could influence the therapeutic management. ITH phenomenon appears to have a relevant role in tumor growth, aggressive behavior and drug resistance. Accordingly, characteristics and consequences of ITH in DTTs should be better analyzed and understood in order to guide clinical practice, improving survival. Consequently, in the present review, we investigated morphological and molecular ITH of DTTs in benign, borderline neoplasms and in malignant entities, summarizing the most significant data. Molecular testing in DTTs documents a high risk for recurrence of cancer associated with BRAFV600E, RET/PTC 1/3, ALK and NTRK fusions, while the intermediate risk may be related to BRAFK601E, H/K/N RAS and PAX8/PPARγ. In addition, it may be suggested that tumor genotype is associated with peculiar phenotype.

Paediatric papillary thyroid cancer: what to expect?

Papillary thyroid cancer is a rare tumour presentation in paediatric age, and although its incidence is rising, it accounts for 1.4% of all malignancies in this age.[1][1] The presentation of...

Potential synergistic effects of sorafenib and CP-31398 for treating anaplastic thyroid cancer with p53 mutations.

Thyroid cancer is the most commonly diagnosed endocrine cancer. Anaplastic thyroid cancer (ATC) is the most aggressive type of thyroid cancer and has a poor prognosis. Loss of p53 function has been reported to lead to poorly differentiated thyroid tumors; therefore, mutant p53 protein can be considered a crucial therapeutic target in patients with ATC. Sorafenib, a multi-kinase inhibitor, has been approved for the treatment of metastatic and differentiated thyroid cancer. Combined targeted therapy, including sorafenib, may be clinically significant for patients with ATC harboring p53 mutations. In the present study, CP-31398, a p53-restoring agent, was used to improve the therapeutic efficacy of sorafenib in SW579 cells, an ATC cell line harboring p53 mutations. The molecular function of CP-31398 was evaluated using western blot analysis and a luciferase reporter assay. The decreased viability of SW579 cells, following CP-31398 treatment, was augmented by sorafenib, and CP-31398 enhanced the antimitogenic effect of sorafenib; thus, sorafenib and CP-31398 synergistically inhibited the growth of SW579 cells. These results indicate a potential clinical application of CP-31398 for patients with ATC harboring p53 abnormalities, since these individuals generally respond poorly to sorafenib alone.

Radioactive Iodine Uptake in Response to Recombinant Human Thyrotropin Stimulation for Thyroid Remnant Ablation in Patients with Differentiated Thyroid Cancer

The vast majority of differentiated thyroid tumours arise from thyroid follicular epithelial cells; papillary cancer corresponds to approximately 85% of cases, whereas about 12% of tumours have follicular histology, including Hurthle cell carcinomas

Impact of the new guidelines of the American Thyroid Association on the treatment of the differentiated thyroid tumor in an Italian center with medium-high volume thyroid surgery

BackgroundThe therapy for differentiated thyroid tumors is currently built upon two cornerstones: the stage of the disease and the new guidelines of the American Thyroid Association, jointly converging to lobohystmectomy for selected cases that meet certain criteria. The aim of the study was to relate these guidelines to the activity of an Italian center with a medium-high volume of thyroidectomies in a region with a high rate of endemic disease of the thyroid.MethodsIn order to conduct the analysis, the clinical records of the last 3 years, including 194 cases of total thyroidectomy and 3 lobohystmectomy, were taken into consideration. There were 46 cases of differentiated thyroid cancer (18 incidental tumors were found during thyroidectomies for benign diseases). Postoperative complications, patient characteristics and the stage of the tumor were assessed in relation to the new ATA guidelines.ResultsAll patients underwent total thyroidectomy, with 2 of them also undergoing lymphadenectomy. The incidence of transient hypoparathyroidism was 19% with 1 case of permanent deficit. No cases of recurrent nerve injury were reported. Twenty-five out of the 28 patients with cancer preoperatively diagnosed were found with more nodules and in 15 of them the nodule had a diameter bigger than 1 cm. All the parameters suggested lobohystmectomy only for one case.The treatment for the differentiated thyroid tumor is still widely discussed. Above all, differences between populations, screening methods and surveillance programs are still evident.ConclusionsThe ATA guidelines applied to our cases, even if limited, have shown limited applicability to our study, mainly due to the high incidence of multinodularity and the size of the nodule: typical characteristics of a region with a high rate of endemic thyroid pathology.

PD-1-expressing B cells suppress CD4+ and CD8+ T cells via PD-1/PD-L1-dependent pathway

B cell-mediated regulatory function is instrumental to the maintenance of tolerance, but may also contribute to immune dysfunction during infectious diseases and malignancies. In this study, we investigated a subset of B cells characterized by PD-1 expression. Data showed that these PD-1+ B cells were rare in peripheral blood, but were significantly upregulated in differentiated thyroid tumors. The PD-1+ B cells also expressed significantly higher level of PD-L1. Continuous, but not short-term, anti-Ig/CD40 L stimulation could upregulate the expression of PD-1 and PD-L1 in B cells. In in vitro experiments, PD-1+ B cells significantly suppressed the proliferation of CD4+ and CD8+ T cells and reduced their viability upon CD3/CD28 stimulation, thus suggesting that these PD-1+ B cells presented regulatory functions. However, unlike other IL-10-secreting Breg cell subsets, the PD-1+ B cells did not express high level of IL-10. Instead, it seemed that PD-L1 was instrumental to the suppressive effects mediated by PD-1+ B cells, since the blockade of PD-L1 significantly increased the proliferation and viability of T cells in the coculture. Interestingly, compared to untreated patients with differentiated thyroid tumor, the thyroidectomy and 131I-treated patients presented significantly lower frequencies of PD-1+ B cells. Together, our investigation demonstrated that the PD-1+ B cells possessed regulatory capacity toward T cell responses, and although rare in peripheral blood, they were significantly enriched in thyroid tumors.

Implications of Na+/I- Symporter Transport to the Plasma Membrane for Thyroid Hormonogenesis and Radioiodide Therapy.

Iodine is a crucial component of thyroid hormones; therefore, a key requirement for thyroid hormone biosynthesis is that iodide (I−) be actively accumulated in the thyroid follicular cell. The ability of the thyroid epithelia to concentrate I− is ultimately dependent on functional Na+/ I− symporter (NIS) expression at the plasma membrane. Underscoring the significance of NIS for thyroid physiology, loss-of-function mutations in the NIS-coding SLC5A5 gene cause an I− transport defect, resulting in dyshormonogenic congenital hypothyroidism. Moreover, I− accumulation in the thyroid cell constitutes the cornerstone for radioiodide ablation therapy for differentiated thyroid carcinoma. However, differentiated thyroid tumors often exhibit reduced (or even undetectable) I− transport compared with normal thyroid tissue, and they are diagnosed as cold nodules on thyroid scintigraphy. Paradoxically, immunohistochemistry analysis revealed that cold thyroid nodules do not express NIS or express normal, or even higher NIS levels compared with adjacent normal tissue, but NIS is frequently intracellularly retained, suggesting the presence of posttranslational abnormalities in the transport of the protein to the plasma membrane. Ultimately, a thorough comprehension of the mechanisms that regulate NIS transport to the plasma membrane would have multiple implications for radioiodide therapy, opening the possibility to identify new molecular targets to treat radioiodide-refractory thyroid tumors. Therefore, in this review, we discuss the current knowledge regarding posttranslational mechanisms that regulate NIS transport to the plasma membrane under physiological and pathological conditions affecting the thyroid follicular cell, a topic of great interest in the thyroid cancer field.

A Carboxy-Terminal Monoleucine-Based Motif Participates in the Basolateral Targeting of the Na+/I- Symporter.

The Na+/iodide (I-) symporter (NIS), a glycoprotein expressed at the basolateral plasma membrane of thyroid follicular cells, mediates I- accumulation for thyroid hormonogenesis and radioiodide therapy for differentiated thyroid carcinoma. However, differentiated thyroid tumors often exhibit lower I- transport than normal thyroid tissue (or even undetectable I- transport). Paradoxically, the majority of differentiated thyroid cancers show intracellular NIS expression, suggesting abnormal targeting to the plasma membrane. Therefore, a thorough understanding of the mechanisms that regulate NIS plasma membrane transport would have multiple implications for radioiodide therapy. In this study, we show that the intracellularly facing carboxy-terminus of NIS is required for the transport of the protein to the plasma membrane. Moreover, the carboxy-terminus contains dominant basolateral information. Using internal deletions and site-directed mutagenesis at the carboxy-terminus, we identified a highly conserved monoleucine-based sorting motif that determines NIS basolateral expression. Furthermore, in clathrin adaptor protein (AP)-1B-deficient cells, NIS sorting to the basolateral plasma membrane is compromised, causing the protein to also be expressed at the apical plasma membrane. Computer simulations suggest that the AP-1B subunit σ1 recognizes the monoleucine-based sorting motif in NIS carboxy-terminus. Although the mechanisms by which NIS is intracellularly retained in thyroid cancer remain elusive, our findings may open up avenues for identifying molecular targets that can be used to treat radioiodide-refractory thyroid tumors that express NIS intracellularly.

Mouse Model of Poorly Differentiated Thyroid Carcinoma Driven by STRN-ALK Fusion

Chromosomal rearrangements of the ALK gene, which lead to constitutive activation of ALK tyrosine kinase, are found in various cancers. In thyroid cancers, ALK fusions, most commonly the STRN-ALK fusion, are detected in papillary thyroid cancer and with higher frequency in poorly differentiated and anaplastic thyroid cancers. Our aim was to establish a mouse model of thyroid-specific expression of STRN-ALK and to test whether this fusion drives the development of thyroid cancer with a propensity for dedifferentiation. Transgenic Tg-STRN-ALK mice with thyroglobulin-controlled expression of STRN-ALK were generated and aged with or without goitrogen treatment. Thyroids from these mice were subjected to histologic and immunohistochemical analysis. Transgenic mice with thyroid-specific expression of STRN-ALK developed poorly differentiated thyroid tumors by the age of 12 months in 22% of mice without goitrogen treatment and in 36% of mice with goitrogen treatment. Histologically and immunohistochemically, the tumors resembled poorly differentiated thyroid cancers in humans, demonstrating a solid growth pattern with sheets of round or spindle-shaped cells, decreased expression of thyroglobulin, and a tendency to lose E-cadherin. In this study, we report a novel mouse model of poorly differentiated thyroid cancer driven by the STRN-ALK oncogene with phenotypic features closely recapitulating human tumor, and with a more pronounced phenotype after additional thyroid-stimulating hormone stimulation.

Neovascular PSMA expression is a common feature in malignant neoplasms of the thyroid.

AimPSMA (prostate-specific membrane antigen) is physiologically expressed in normal prostate tissue and over expressed in prostate cancer cells, therefore constituting a potential target for antibody-based radioligand therapy. Very recent imaging findings reported PSMA-PET/CT uptake in various thyroid lesions. We were therefore encouraged to systematically analyse PSMA expression in different benign and malignant thyroid lesions.MethodsImmunohistochemistry was used to detect PSMA expression in 101 thyroid lesions, while neovasculature was identified by CD34 immunostaining.ResultsPSMA expression in the neovasculature was significantly more frequent in malignant tumors (36/63; 57.1%) compared to benign diseases (5/38; 13.2%; p = 0.0001). In addition, PSMA expression levels in the neovasculature of poorly and undifferentiated thyroid cancers were significantly higher compared to differentiated thyroid tumors (p = 0.021). However, one case with a strong expression in follicular adenoma was identified.ConclusionsWe conclude that neovascular PSMA expression is common in thyroid cancer but may also rarely be found in benign thyroid diseases, such as follicular adenoma. High expression in the tumor-associated neovasculature is predominantly found in poorly differentiated and undifferentiated (anaplastic) thyroid cancer. This knowledge is highly relevant when interpreting PSMA/PET-CT scans from patients with prostate cancer. In addition, our findings might provide a rationale for further evaluation of PSMA-targeted anti-neovascular or radioligand therapy in metastatic dedifferentiated thyroid cancer.

Expression of PSMA in Thyroid follicular neoplasms: Utility for differentiating between benign from malignant lesions

Back ground: Prostate-Specific membrane Antigen has been known as a tumor associated neovasculature marker in some solid malignant tumors and targeting of that by cytotoxic- conjugated antibody can represent powerful tool for vascular targeted therapy in malignant tumors. In thyroid, it appears that angiogenesis factors are involved in neoplastic growth and aggressiveness of tumors. This study was conducted to evaluate the expression of PSMA as an angiogensis factor by immunohistochemistry in neovasculature of thyroid follicular neoplasms to determine its usefulness for distinguishing between adenoma and carcinoma . Methods: Paraffin Blocks of formalin fixed samples representing 48 cases of Follicular Thyroid adenoma and 15 cases of Follicular Thyroid Carcinoma were evaluated. Results: Among Carcinomas, capsular and vascular invasion were present in 12 and 11 cases , respectively. The intensity of PSMA staining was significantly higher in carcinoma group(p=0.028). However, no significant difference in extent of PSMA expression in adenoma and carcinoma groups was observed(p=0.239).Thyroid follicular cells in adenoma, carcinoma also non neoplastic area were negative for PSMA. Conclusion: Our findings do not support usefulness of PSMA in differentiating between FTA and FTC. However ; expression in neovasculature of differentiated thyroid tumors can represent a potential utility for PSMA-targeted radionuclide therapy in advanced differentiated thyroid cancers. DOI:10.21276/APALM.1511

Oncogenes, mitochondrial metabolism, and quality control in differentiated thyroid cancer.

Thyroid cancer is one of the most common malignancies of endocrine organs, and its incidence rate has increased steadily over the past several decades. Most differentiated thyroid tumors derived from thyroid epithelial cells exhibit slow-growing cancers, and patients with these tumors can achieve a good prognosis with surgical removal and radioiodine treatment. However, a small proportion of patients present with advanced thyroid cancer and are unusually resistant to current drug treatment modalities. Thyroid tumorigenesis is a complex process that is regulated by the activation of oncogenes, inactivation of tumor suppressors, and alterations in programmed cell death. Mitochondria play an essential role during tumor formation, progression, and metastasis of thyroid cancer. Recent studies have successfully observed the mitochondrial etiology of thyroid carcinogenesis. This review focuses on the recent progress in understanding the molecular mechanisms of thyroid cancer relating to altered mitochondrial metabolism.

New Insights in Thyroid Cancer and p53 Family Proteins.

Thyroid cancers are common endocrine malignancies that comprise tumors with different clinical and histological features. Indeed, papillary and follicular thyroid cancers are slow-growing, well-differentiated tumors, whereas anaplastic thyroid cancers are undifferentiated neoplasias that behave much more aggressively. Well-differentiated thyroid carcinomas are efficiently cured by surgery and radioiodine, unlike undifferentiated tumors that fail to uptake radioactive iodine and are usually resistant to chemotherapy. Therefore, novel and more effective therapies for these aggressive neoplasias are urgently needed. Whereas most genetic events underlying the pathogenesis of well-differentiated thyroid cancers have been identified, the molecular mechanisms that generate undifferentiated thyroid carcinomas are still unclear. To date, one of the best-characterized genetic alterations leading to the development of poorly differentiated thyroid tumors is the loss of the p53 tumor suppressor gene. In addition, the existence of a complex network among p53 family members (p63 and p73) and their interactions with other factors that promote thyroid cancer progression has been well documented. In this review, we provide an update on the current knowledge of the role of p53 family proteins in thyroid cancer and their possible use as a therapeutic target for the treatment of the most aggressive variants of this disease.