Thyroid Specimens Research Articles

Perfluorooctane Sulfonate and Perfluorooctanoic Acid in Surgical Thyroid Specimens of Patients with Thyroid Diseases

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are ubiquitous compounds that may act as endocrine disruptors, neurotoxic agents, and fetal development perturbing substances and may also be carcinogenic, as recently demonstrated in experimental animal models. There is little information on the potential for these compounds to affect the thyroid. Therefore, this study was performed to measure the intrathyroidal levels of PFOA and PFOS in surgical specimens of thyroid glands and to determine if there was a relationship between the concentrations of these substances and the clinical, biochemical, and histologic phenotype of the patients from whom the thyroids were obtained. We also sought to determine if there was a relationship between tissue and serum levels of both PFOA and PFOS. PFOA and PFOS were measured in 28 patients undergoing thyroid surgery for benign (15 multinodular goiters and 7 Graves' disease) and malignant (5 papillary and 1 follicular carcinoma) thyroid disorders. PFOA and PFOS were detectable in all surgical specimens of thyroid tissue. Their median concentrations were 2.0 ng/g (range = 0.4-4.6 ng/g) and 5.3 ng/g (range = 2.1-44.7), respectively. Intrathyroidal concentrations of PFOA and PFOS were similar in the thyroids of patients with thyroid diseases as in thyroid glands obtained at autopsy. There was no relationship between the intrathyroidal concentrations of either PFOA or PFOS and the underlying thyroid disease. A significant correlation between the serum and the tissue levels of PFOS was found in all patients. The serum concentrations of PFOA and PFOS were significantly higher than those in the correspondent surgical specimens. These observations do not support the view that PFOA and PFOS are actively concentrated in the thyroid. PFOA and PFOS, however, are both found in surgical and autopsy thyroid specimens. Therefore, further studies to determine if they have disrupting effects in thyroid cells or tissue, and studies to compare populations with and without these compounds in their thyroid glands, are important.

Autophagy: A new target for advanced papillary thyroid cancer therapy

Autophagy is a conserved response to stress that facilitates cell survival in some contexts and promotes cell death in others. We sought to characterize autophagy in papillary thyroid cancer (PTC), and to determine the effects of autophagy inhibition on chemosensitivity and radiosensitivity. The human thyroid papillary carcinoma cell lines TPC-1 and 8505-C were treated with doxorubicin or radiation in the presence or absence of the autophagy-specific inhibitor 3-methyladenine (3-MA). Although light chain 3 (LC3)-II protein levels were undetectable in normal thyroid and PTC specimens at baseline, doxorubicin exposure induced LC3-II expression and the formation of autophagosomes. Both PTC cell lines expressed low levels of LC3-II under standard conditions. Treatment of these cells with doxorubicin strongly induced LC3-II expression and the formation of autophagosomes; however, doxorubicin-mediated induction of LC3-II was abrogated by 3-MA. Moreover, 3-MA significantly increased the doxorubicin IC(50) in both PTC cell lines. Radiation exposure also induced LC3-II expression. Treatment with 3-MA abrogated the radiation-induced increase in LC3-II in both cell lines and reduced radiosensitivity by 49% and 31% in 8505-C and TPC-1 cells, respectively. Autophagy inhibition promotes PTC resistance to doxorubicin and radiation. Therefore, autophagy activation may be a useful adjunct treatment for patients with PTC that is refractory to conventional therapy.

Thyrolipoma and thyrolipomatosis: 5 case reports and historical review of the literature

Because thyrolipoma (adenolipoma of thyroid) and thyrolipomatosis (diffuse lipomatosis of thyroid) are distinctively rare conditions with only few cases reported in the literature, we are reporting 5 additional cases. All the 5 patients were adult females, with ages from 38 to 79 years, who presented with thyroid masses. Four of the patients had normal thyroid function tests and one had mild hypothyroidism. All patients received partial or total thyroidectomy. The thyroid specimens showed either circumscribed yellow-tan masses (cases 1, 2, and 3) or diffuse yellow-brown discoloration (cases 4 and 5). Histologic examination revealed abundant mature fat infiltrating the affected thyroid tissue in 3 distinct patterns: (1) fat infiltration limited to follicular adenomas (thyrolipoma); (2) fat diffusely infiltrating throughout the thyroid gland (thyrolipomatosis); or (3) fat infiltration involving both follicular adenoma and their surrounding thyroid tissue. Because of the rarity of thyroid fat-containing lesions, confusion in differential diagnosis may occasionally occur. It is important to be aware during frozen section that these lesions may present as extrathyroidal nodules, which can be radioactive on intraoperative scan for parathyroid glands. In addition, a papillary thyroid carcinoma was also identified in one case of thyrolipomatosis. All patients recovered well after surgery and there has been no recurrence of the lesions after 1 to 24 years of clinical follow-up. In summary, we are reporting 5 rare cases of thyrolipoma and thyrolipomatosis with distinct histologic patterns. Previously reported cases of thyrolipomatosis were reviewed and analyzed with the current cases.

Solid Cell Nests in Hashimoto’s Thyroiditis Sharing Features with Papillary Thyroid Microcarcinoma

Solid cell nests (SCN) associated with Hashimoto's thyroiditis may show some atypical nuclear features including prominent nuclear grooves, enlarged overlapping nuclei and nuclear clearing. These features are sometimes mistaken for papillary thyroid microcarcinomas especially when the SCN are numerous. We reviewed SCN associated with Hashimoto's thyroiditis in 12 patients selected from 1,420 archival routinely processed formalin-fixed, paraffin-embedded thyroid specimens of Hashimoto's thyroiditis in which there was more than ten SCN per slide. In addition to the atypical nuclear features, there was a distinct eosinophilic basement membrane surrounding the SCN. Immunohistochemical analysis showed that the SCN were strongly positive for p63, stained weakly for TTF-1 and were negative for thyroglobulin, HBME-1, and calcitonin. This was compared to papillary thyroid microcarcinomas which were strongly positive for thyroglobulin, TTF-1, HBME-1, and variably positive for p63, while calcitonin and chromogranin were negative. These histological and immunophenotypic features can be used to distinguish SCN from papillary thyroid microcarcinomas associated with Hashimoto's thyroiditis.

Inhibitory effect of Kangjia Pill (抗甲丸) on thyrocyte proliferation in rat goiter model

To investigate the inhibitory effects of Kangjia Pill (KJP) on the cell proliferation in rat goiter model induced by methimazole (MMI). Fifty-six Wistar rats were randomly divided into four groups: the normal group, MMI model group (MMI), low dose of KJP group (LKJP), and high dose of KJP (HKJP). Except the normal group (20 rats), the other groups (12 rats in each) were given 0.04% (w/v) MMI through the drinking water until the end of the experiment. One week later, the rats in the LKJP and HKJP groups were given KJP by gastrogavage at the dose of 250 mg/(kg x d) and 1,000 mg/(kg x d), respectively for 12 weeks. The relative thyroid weight (mg/100 g body weight) of each rat was accessed. The expression of proliferating cell nuclear antigen (PCNA) was determined by immunohistochemistry, and the correlation analysis between the PCNA positive thyrocytes and the relative thyroid weight was performed. The expressions of PCNA and cyclin D1 were examined with Western blotting. After KJP treatment for 12 weeks, compared with the MMI group, the relative thyroid weight of the HKJP group decreased significantly, and the positive thyrocyte populations of PCNA in the two KJP groups reduced markedly (all P<0.05). The correlation analysis showed that PCNA was closely correlated with thyrocyte proliferation (r=0.685, P<0.05). KJP significantly decreased the protein expression of PCNA and cyclin D1 in the thyroid specimens (P<0.05), the high dose showed better effects. KJP played a therapeutic role via inhibiting cell proliferation in the rat goitrous glands.

Spindle epithelial tumor with thymus-like elements of the thyroid: a multi-institutional case series and review of the literature

Background/Purpose Spindle epithelial tumor with thymus-like elements (SETTLE) is a rare tumor of the thyroid observed in children and adolescents. We present a case series of 3 patients with SETTLE, focusing on the clinical and pathologic features of this rare tumor. Methods Three male patients presented at ages 4.5, 6.5, and 7 years with a right thyroid mass. All were treated by standard hemithyroidectomy. None had evidence of distant metastases at presentation. The diagnosis of SETTLE was confirmed at the time of the initial operation in 2 of the 3 patients. Results All patients had uneventful postoperative courses. Two patients remain disease-free 4 and 7 years postresection, respectively. One patient presented 10 years after resection with shortness of breath and hemoptysis secondary to multiple bilateral parenchymal lung metastases. This patient received chemotherapy against the epithelial components of the tumor with a 25% response based on imaging studies. Conclusion Spindle epithelial tumor with thymus-like elements is rare tumor that should be suspected if spindle elements are observed in the resected thyroid specimen. Because these patients may present with delayed metastases, follow-up is recommended. However, chemotherapy against specific tumor elements is only marginally effective.

Thyroglobulin may affect telomerase activity in thyroid follicular cells

Telomerase (TA) activity is known to be present in malignant tumor cells, but not in most somatic differentiated cells. TA shows relatively high activity in thyroid cancer cells, but reports vary. This fact prompted us to elucidate whether cell component inhibitors of TA in the thyroid follicles can modulate its activity. The activity of TA extracted from Hela cells was inhibited by mixing with the supernatant fraction of human thyroid tissue extract. To examine the effect of iodine, thyroid hormones (ℓ-T3 and ℓ-T4) and human thyroglobulin (hTg) contained in the thyroid follicles, ℓ-T3, ℓ-T4 and hTg were added to the TRAP assay system in vitro, using TA from Hela cells. Iodine, ℓ-T3 and ℓ-T4 did not affect TA activity, but hTg inhibited the TA activity in a dose-dependent manner (IC50 of hTg: ca 0.45 μM: inhibiting concentration of hTg was from 0.15 μM to 3.0 μM). The hTg inhibition was not evident in the RT-PCR system, suggesting no effect of hTg on Taq DNA polymerase activity. The hTg inhibition of TA activity was attenuated by dNTP but not significantly by TS primer. These data suggest that hTg contained in thyroid follicular cells of various thyroid diseases may affect the TA activity measured in biopsied thyroid specimens, and that the reduction of the TA activity by hTg may induce slow progression and growth, and low grade malignancy of thyroid cancer, particularly differentiated carcinoma.

Persistent Infection of a Carcinoma Thyroid Cell Line with Coxsackievirus B

Viral infections are described as environmental factors that are implicated in various thyroid diseases. The role of enteroviruses (EV) in the pathogenesis of thyroid diseases has been suspected. Recently, we found that EV RNA could be detected in postoperative thyroid specimens. We decided to investigate the infection of a human thyroid cell line with coxsackievirus B4 (CVB4). The wild-type human thyroid carcinoma cells K1 were inoculated with CVB4E2 at 2.1 x 10(7) TCID50/mL. The titer of the virus progeny was determined every 3 days on HEp-2 cells. CVB replication at the molecular level was monitored by searching for intracellular viral genomes using reverse transcription (RT)-polymerase chain reaction (PCR). EV VP1 capsid protein was detected by indirect immunocytofluorescence staining. Cell viability was determined by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) absorbance, and the nuclear morphology was assessed by Hoechst Dye staining. Infectivity assays with CVB4E2 revealed an increase in viral titers. Virus production decreased thereafter, but was not stopped by serial subculture for 24 days after infection. Detection of intracellular positive and negative viral RNA strands by RT-PCR was positive between days 1 and 14 postinfection (p.i.), and by semi-nested RT-PCR up to 24 days. K1 cell cultures infected with CVB4 were stained positively for EV VP1: the number of VP1-positive cells decreased rapidly within 6 days and remained low up to the end of culture. Compared with mock-infected cultures, viability in CVB4-infected cultures was around 100% up to 24 days. Cells with strongly fluorescent nuclei and/or fragmented nuclei were observed. We demonstrate for the first time that CVB4 could replicate in thyroid cells and could persist, with predominance of viral negative RNA strands for up to 24 days p.i. without obvious cytopathic effect. Our results suggest that CVB4 may lead to thyroid cell apoptosis. Further studies are needed to determine whether CVB could play a role in thyroid pathologies.

La valeur de l’examen extemporané dans la chirurgie des nodules thyroïdiens. À propos de 409 cas

The purpose of this study was to assess the value of intraoperative frozen section diagnosis in thyroid surgery and determine its limitations. This retrospective study examined the results of 409 frozen sections of thyroid specimens analyzed over the 4-year period and their correlations with the final histological examination. In our series, frozen section diagnosis was concordant with subsequent histopathological examination in 96.6% of cases, discordant in 3.4%. All discordances were due to false-negative diagnoses. Non-false-positive result was found. The global specificity of frozen section analysis for all histological subtypes was 100% and its sensitivity was 68.2%. The frozen section evaluation of thyroid neoplasm is highly accurate and specific. A high degree of specificity with an acceptable sensitivity is requested. However, the frozen section examination has still some limits in the diagnosis of microfollicular lesions.

Effects of Kang-Jia-Wan, a Chinese medicinal herb officinal, on apoptosis induction in goiter of rats

Ethnopharmacological relevance Kang-Jia-Wan (KJW), a traditional Chinese herbal medicine, is widely used to treat goiter in the clinics in China. Aim The mechanisms by which KJW treats goiter are unclear. It is known that insufficient apoptosis of thyrocytes is involved in the formation of goiter. Here, we investigated whether KJW could induce apoptosis in goiter of rats given methimazole (MMI). Materials and methods Fifty-six Wistar rats were randomly separated into four groups: normal, MMI, MMI + low-dose KJW and MMI + high-dose KJW. Except for the normal group (20 rats), all groups (each with 12 rats) were given 0.04% (w/v) MMI in their drinking water. One week later, the rats in MMI + low- and high-dose KJW groups were orally supplemented with KJW at 250 mg/kg d −1 and 1000 mg/kg d −1, respectively. Results After KJW treatment for 12 weeks, the relative thyroid weight (mg/100 g body weight) of the MMI + high-dose KJW group decreased significantly. Features of apoptosis were also apparent in thyroid tissues of rats given KJW treatment. Importantly, KJW markedly increased the caspase-3 and Fas protein expression, in a dose-dependent manner, in the thyroid specimens. Conclusions These results showed that KJW played a therapeutic role via apoptosis induction in the goitrous glands.

Detection of enterovirus RNA in postoperative thyroid tissue specimens

Autoimmune thyroiditis is a very common disease. A genetic predisposition and environmental factors such as viruses are thought to contribute to the development of autoimmune thyroiditis. Enteroviruses, which are involved in other autoimmune diseases, are attractive candidates. To investigate the presence of enteroviral genome sequences in postoperative thyroid tissues with lymphocytic infiltration, a common histological feature of thyroiditis. Postoperative thyroid specimens collected prospectively from 86 patients were blindly frozen at -80 degrees C. The presence of EV genome sequences in the samples was blindly investigated by real-time RT-PCR. Clinical data, histological findings and levels of anti-TPO antibodies were collected. EV-RNA detection was positive (up to 36 cycles) or weakly positive (37-39 cycles) in 22 out of 86 patients (25%). EV-RNA (positive or weakly positive signal) was detected in 5 out of 27 (18.5%) thyroid specimens with lymphocytic infiltration, and in 17 out of 59 (29%) thyroid specimens without lymphocytic infiltration (P = 0.4). No correlation was observed between EV-RNA detection in thyroid and the presence of anti-TPOAb. EV-RNA was detected in 3 out of 11 patients histologically diagnosed as thyroiditis (27.3%) and in 18 out of 74 patients (24.3%) with thyroid tumours (multinodular goitre, adenoma and carcinoma) (P = 0.5) and in one patient with a normal thyroid. EV-RNA can be detected in thyroid tissue from patients with various thyroid diseases, but there is no relationship between the presence of EV-RNA and thyroiditis. Further studies are needed to clarify the role of EV in thyroid diseases.

A minute focus of extranodal marginal zone B-cell lymphoma arising in Hashimoto thyroiditis diagnosed with PCR after laser capture microdissection: a case report

BackgroundPrimary thyroid gland lymphomas are uncommon tumours that occur in the setting of lymphocytic thyroiditis or Hashimoto's disease in almost all cases. In this condition a distinction between an inflammatory lymphoid infiltrate and a low grade lymphoma may be extremely difficult and precise criteria are necessary for a correct diagnosis.Patient and methodsWe report a case of a minute focus of primary extranodal marginal zone B-cell lymphoma (EMZBCL), incidentally discovered in a 63-year-old man with Hashimoto thyroiditis (HT) and diagnosed by means of polymerase chain reaction (PCR) after laser capture microdissection.The histological examination of surgical specimen confirmed the diagnosis of HT and showed a minute focus of dense lymphoid infiltrate (less than 4 mm in diameter), composed by centrocyte-like cells forming MALT balls. Immunoistochemistry was not useful. A microscopic focus of EMZBCL was suspected on the basis of morphological features. PCR assays revealed the rearrangement of the heavy chain of immunoglobulins only in the microdissected suspicious area, confirming the diagnosis of EMZBCL.ConclusionOur finding suggests that in cases of autoimmune thyroiditis a careful examination of the thyroid specimen is warranted, in order to disclose areas or small foci of lymphomatous transformation. Furthermore, in difficult cases with doubtful immunohistological findings, ancillary techniques, such as molecular studies, are necessary for a conclusive diagnosis.

Hemithyroidectomy for benign thyroid disease: who needs follow‐up for hypothyroidism?

To identify the incidence and possible risk factors for the development of hypothyroidism following hemithyroidectomy and to determine a simple protocol for the post-op monitoring of thyroid function. Prospective study. Tertiary Referral Centre. Eighty-two consecutive patients who underwent hemi-thyroidectomy between May 2003 and May 2005 were included. The clinical and pathological factors were obtained and statistically analysed. Eighteen per cent of patients became hypothyroid post-operatively. Multivariate analysis demonstrated that risk factors for hypothyroidism following hemithyroidectomy included a pre-operative [TSH] >1.6 microIU/L [P = 0.008, hazard ratio (HR) 14, 95% confidence interval (CI) 2-54] and lymphocytic infiltration graded 3+ or more (P < 0.001, HR 42, 95% CI, 8-195%). There was no relationship between age, sex or weight of resected tissue and the risk of hypothyroidism. Patients with raised pre-operative [TSH] or with lymphocytic infiltration of their thyroid specimen should undergo regular testing of thyroid function within the first year of surgery. In all other patients, thyroid function at 12 months is sufficient.

Thyrocytes contribute to their own demise: the role of interleukin-18 in Hashimoto's thyroiditis

To investigate the IL-18 expression in the thyroid tissues of Hashimoto's thyroiditis (HT) and its cellular localization and the effect of interferon-gamma (IFN-gamma) on the interleukin- (IL)-18 expression in thyrocytes. RT-PCR and immunohistochemistry were used to detect the IL-18 expression and its cellular localization in the thyroid tissues biopsy specimens of 6 HT patients with normal thyroid function, 6 normal thyroid specimens resected from patients with pharyngeal carcinoma, and 16 specimens of thyroid tissues adjacent to the thyroid adenoma obtained during operation. Thyrocytes were isolated, cultured, and exposed to IL-1beta, tumor necrosis factor-alpha (TNF-alpha), or IFN-gamma for 48 h. RT-PCR and Western blotting were used to detect the IL-18 expression. IL-18 mRNA expression was at an extremely low levels in the normal thyroid tissues and at a significantly higher level in the thyroid tissues of HT. Immunohistochemical staining showed that IL-18 expression was augmented in the thyroid tissues of HT and was mainly localized in the thyroid follicular cells. The IL-18 mRNA expression in the isolated human thyrocytes was dose-dependently elevated by IFN-gamma rather than TNF-alpha or IL-1beta. Western blotting showed that pro-IL-18, but not mature IL-18, was detected in the lysates of the cultured human thyrocytes and the expression of pro-IL-18 was increased by IFN-gamma. IL-18 expression is elevated in the thyroid follicular cells of HT. IL-18 is constitutively expressed in the isolated human thyrocytes and its expression is up-regulated by IFN-gamma. Therefore, interplay between IL-18 and IFN-gamma may have an important role in the thyrocytes destruction in HT.

No restriction of intrathyroidal T cell receptor V alpha families in the thyroid of Graves' disease.

Recently it has been reported that the intrathyroidal T cells in Graves' disease display restriction in V alpha T cell receptor (TcR) gene family usage, although this is not found with TcR V beta gene families in the same individuals. We have performed a qualitative analysis of TcR V alpha family usage in 12 patients with Graves' disease by reverse transcription and polymerase chain reaction (PCR) amplification of RNA extracted from isolated, unstimulated intrathyroidal lymphocytes and from snap-frozen whole thyroid specimens. No restriction was observed, with 10-15 V alpha gene families being amplified in all cases. The pattern of usage was similar to that in peripheral blood lymphocytes derived from normal subjects (n = 3) and from patients with Graves' disease (n = 3), as well as that present in the thyroids of patients with non-autoimmune toxic multinodular goitre (n = 4). These results indicated that there is no marked restriction of the unselected intrathyroidal T cell population in patients with Graves' disease who have been treated with antithyroid drugs.

Expression of intercellular adhesion molecule-1 (ICAM-1) on thyroid epithelial cells in Hashimoto's thyroiditis but not in Graves' disease or papillary thyroid cancer.

In order to study the possible role of antigen-independent adhesion systems in thyroid autoimmunity, we evaluated by indirect immunofluorescence the expression of lymphocyte functional antigen-1 (LFA-1) and its ligand ICAM-1 on mononuclear cell infiltrates (when present) and thyroid follicular cells of four patients with Hashimoto's thyroiditis, 30 with Graves' disease, five with papillary cancer, two with follicular adenoma, and two normal thyroid specimens. The expression of MHC class I and class II antigens was also evaluated. Most mononuclear infiltrates were LFA-1 positive, as expected. A positivity for ICAM-1 on follicular cells was observed in three out of four Hashimoto's thyroiditis specimens; such a phenomenon was totally absent in Graves' disease or any other pathological condition, or in normal tissue. MHC class II expression on thyrocytes was observed in all the patients with Hashimoto's thyroiditis, in 27 out of 30 with Graves' disease and in three out of five papillary cancer specimens.

Identification of an adult stem/progenitor cell-like population in the human thyroid

There is evidence that tissue-specific stem cells reside in certain adult tissues. Their specific properties remain elusive, because they are rare and heterogeneous in parent tissues; furthermore, technical difficulties have been encountered in the identification and characterization of their progeny. The aim of this study was to isolate stem/progenitor cells from the human thyroid. We devised a method based on the enzymatic digestion of fresh surgical thyroid specimens, followed by culture of cells in the presence of epidermal growth factor and basic fibroblast growth factor. We also used markers that identify and characterize these cells. Spheroids with self-replicative potential were obtained from all thyroid specimens. The isolated population contained a subset of CD34+ CD45- cells and it was able, in differentiation conditions, to generate follicles with thyroid hormonal production. In support of the plasticity concept, we obtained evidence that, when most freshly isolated spheroids were co-cultured with a neuroblastoma cell line, they produced progeny expressing the neuronal marker beta-tubulin III. Spheroids were also able to undergo adipogenic differentiation when cultured in adipogenic medium. We conclude that a predominant functional type of stem/progenitor cell exists within the thyroid, with an intrinsic ability to generate thyroidal cells and the potential to produce non-thyroidal cells.

Regulation of tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by DJ-1 in thyroid cancer cells

DJ-1, a cancer-associated protein protects cells from multiple toxic stresses. The expression of DJ-1 and its influence on thyroid cancer cell death has not been investigated so far. We analyzed DJ-1 expression in human thyroid carcinoma cell lines and the effect of DJ-1 on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. DJ-1 was expressed in human thyroid carcinoma cell lines; small interfering RNA-mediated downregulation of its levels significantly sensitized thyroid carcinoma cells to TRAIL-induced apoptosis, whereas the forced exogenous expression of DJ-1 significantly suppressed cell death induced by TRAIL. We also report here that TRAIL-induced thyroid cancer cell apoptosis is mediated by oxidative stress and that DJ-1, a potent nutritional antioxidant, protects cancer cells from apoptosis at least in part by impeding the elevation of reactive oxygen species levels induced by TRAIL and impairing caspase-8 activation. Subsequently, we investigated DJ-1 expression in 52 normal and 74 primary thyroid carcinomas from patients of China Medical University. The protein was not detectable in the 52 specimens of normal thyroid, while 70 out of 74 analyzed carcinomas (33 out of 33 follicular, 17 out of 19 papillary, 12 out of 13 medullar, and 8 out of 9 anaplastic) were clearly positive for DJ-1 expression. Our data demonstrated that DJ-1 is specifically expressed in thyroid carcinomas and not in the normal thyroid tissue. In addition, the protein modulates the response to TRAIL-mediated apoptosis in human neoplastic thyroid cells, at least partially through its antioxidant property.

TFF3-Based Candidate Gene Discrimination of Benign and Malignant Thyroid Tumors in a Region with Borderline Iodine Deficiency

With the advent of microarray technology, increasing numbers of marker genes are proposed to distinguish benign and malignant thyroid lesions. However, most markers await confirmation through independent studies. In this paper, we re-evaluate the diagnostic potential of 10 proposed candidate genes in benign and malignant thyroid pathologies in a region with borderline iodine deficiency. Quantitative real-time PCR was performed for CCND2, PLAB, PCSK2, HGD1, TFF3, B4GALT, LGALS3, ETS1, ADM3, and TG in 150 thyroid specimens, including 52 benign thyroid nodules (28 follicular adenoma and 24 adenomatous nodules), 52 corresponding normal thyroid tissues, 20 follicular carcinomas, 20 papillary carcinomas, and six undifferentiated carcinomas. On a single-gene basis, significant differences in mRNA expression were found for TFF3, PLAB, and ADM3 in benign thyroid nodules and thyroid malignancy. Using two-marker gene sets, we identified 11 combinations, which allowed both a distinction of benign and malignant thyroid nodules and a discrimination of follicular adenoma and carcinoma. However, for cancer prediction, analysis of a minimum of six genes per sample was necessary and allowed correct prediction of a benign thyroid lesion and thyroid cancer with 94% accuracy in the most discriminative set (TFF3/PLAB/TG/ADM3/HGD1/LGALS3). We confirm the applicability of a number of recently proposed marker genes for the distinction of benign and malignant thyroid tumor and suggest that their diagnostic usefulness is independent of the iodide supply. We propose that the most discriminative marker set identified in our validation study together with marker combinations proposed by other investigators should now be evaluated in multicenter trials.

So-called oncocytoma of the thyroid (author's transl)

There were 68 thyroids with oncocytic cell changes among thyroid specimens from 2476 thyroid operations performed between 1969 and 1978. In 12 instances there were merely Hürthle cell nests, in 13 there was an oncocytic carcinoma and in 43 oncocytic adenoma. Thyroidectomy was the preferred treatment for Hürthle-cell carcinoma. Five patients were no longer suitable for radical operation, in one there was a recurrence. If there is a potentially malignant oncocytoma, hemithyroidectomy should be performed and careful follow-up is necessary. There was no recurrence maximally 82 months postoperatively.