Catalysis by oxide-supported clusters of iridium and rhodium: hydrogenation of ethene, propene, and toluene.

The hydrogenation reactions of ethene, propene, and toluene were used as probes of the catalytic properties of small clusters of rhodium (Rh6) and of iridium (Ir4 and Ir6) (as well as of larger aggregates of these metals) on oxide supports (gamma-Al2O3, MgO, and La2O3). The catalysts were characterized in the working state by extended X-ray absorption fine structure (EXAFS) spectroscopy, providing evidence of the cluster structures and cluster-support interactions; by infrared spectroscopy, providing evidence of hydrocarbon adsorbates and possible reaction intermediates on the clusters; and by kinetics of the hydrogenation reactions. The EXAFS data indicate that the metal clusters, while remaining intact and maintaining their bonding to the support during catalysis, underwent slight rearrangements to accommodate reactive intermediates. As the concentrations of reactive intermediates such as pi-bonded alkenes and alkyls on the clusters increased, the cluster frames swelled, and the clusters flexed away from the support. The data indicate self-inhibition of reaction by adsorbed hydrocarbons and differences between ethene hydrogenation and propene hydrogenation that may arise primarily from different adsorbate-adsorbate interactions.

Percutaneous ethanol injection for treatment of cervical lymph node metastases in patients with papillary thyroid carcinoma.

OBJECTIVE: The objective of this study was to evaluate the technique, efficacy, and side effects of percutaneous ethanol injection in patients with limited cervical nodal metastases from papillary thyroid carcinoma. SUBJECTS AND METHODS: Fourteen patients who had undergone thyroidectomy for papillary thyroid carcinoma presented with limited nodal metastases (one to five involved nodes) in the neck between May 1993 and April 2000. All patients had received previous iodine-131 ablative therapy with a mean total dose per patient of 7,548 MBq. Ten of the patients either were considered poor surgical candidates or preferred not to have surgery, and all were unresponsive to iodine-131 therapy. Each metastatic lymph node was treated with percutaneous ethanol injection, and patients received both clinical and sonographic follow-up. RESULTS: Twenty-nine metastatic lymph nodes in our 14 patients were injected. Mean sonographic follow-up was 18 months (range, from 2 months to 6 years 5 months). All treated lymph nodes decreased in volume from a mean of 492 mm(3) before percutaneous ethanol injection to a mean volume of 76 mm(3) at 1 year and 20 mm(3) at 2 years after treatment. Six nodes were re-treated 2-12 months after initial percutaneous ethanol injection because of persistent flow on color Doppler sonography (n = 4), stable size (n = 1), or increased size (n = 1). Two patients developed four new metastatic nodes during the follow-up period that were amenable to percutaneous ethanol injection. Two patients developed innumerable metastatic nodes that precluded retreatment with percutaneous ethanol injection. No major complications occurred. All patients experienced long-term local control of metastatic lymph nodes treated by percutaneous ethanol injection. In 12 of 14 patients, percutaneous ethanol injection was successful in controlling all known metastatic adenopathy. CONCLUSION: Sonographically guided percutaneous ethanol injection is a valuable treatment option for patients with limited cervical nodal metastases from papillary thyroid cancer who are not amenable to further surgical or radioiodine therapy.

Anaplastic thyroid carcinoma: a 50-year experience at a single institution.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is among the most aggressive of human malignancies. However, there have been few large studies of histologically well-defined ATC. We report the results of a 50-year experience of this lethal malignancy. METHODS: We reviewed all cases of ATC managed in this institution between 1949 and 1999. One pathologist (J.R.G.) reviewed all pathologic material. Clinical details were obtained from medical records, and current status of all patients was determined. RESULTS: There were 134 cases, with a female-to-male ratio of 1.5:1 and a mean age of 67 years. Benign thyroid disease was present in 27 cases (20%) and well-differentiated thyroid carcinoma in 31 (23%). Sixty-two patients (46%) had distant metastases at diagnosis, and 98% of the tumors were locally invasive. Primary treatment was surgical for 96 patients (72%). Complete resection was achieved in 29 cases (30%), with "minimal residual disease" in 25. Neither extent of operation nor completeness of resection affected survival (P > .4). Postoperative radiotherapy gave slightly longer median survival (5 vs 3 months), which was not significant (P < .08). Multimodal therapy, including operation, chemotherapy, and radiotherapy, did not improve survival. CONCLUSIONS: The outlook for patients with ATC remains grim. Novel treatments for ATC are desperately needed.

Immunohistochemical analysis of sodium iodide symporter expression in metastatic differentiated thyroid cancer: correlation with radioiodine uptake.

The ability of thyroid cancers to concentrate radioiodine (RAI) is dependent, in part, upon the expression and functional integrity of the sodium iodide symporter (NIS). However, some differentiated thyroid carcinomas (DTCs) and most undifferentiated thyroid carcinomas lack the ability to concentrate iodide and are thereby insensitive to 131I therapy. Variation of NIS protein expression may be an important factor in this behavior. We wished to determine whether NIS protein expression in primary DTC tumors correlated with the subsequent RAI uptake by metastatic lesions in the same patients. We obtained paraffin-embedded tissue specimens from 60 patients with metastatic thyroid cancer who had undergone total or near-total thyroidectomy at the Mayo Clinic for DTC and had known presence or absence of RAI uptake in their tumor deposits determined by total body scanning after thyroid hormone withdrawal. Tissue sections from the primary intrathyroidal tumors were subjected to immunostaining (IS) using a monoclonal antibody against human NIS. Slides were subsequently examined for specific IS by two independent reviewers. For each patient, whole body scan (WBS) uptake was recorded, and correlation between results of IS and WBS was analyzed. Of 43 patients with a positive WBS, 37 also had positive IS of their tumors. In six patients with negative IS, a positive WBS was documented, and in three of these cases TSH at the time of surgery was less than 0.3 mIU/liter. Of the 17 patients with negative WBS, 10 were also negative on IS. Positive IS accurately predicted a positive scan in our study in 84% of cases; the ability of the IS to detect all cases with a positive scan was 86%, and it increased to 90% when patients who were receiving thyroid hormone therapy at the time of surgery were excluded from the analysis. Overall, the results of our retrospective study suggest that NIS IS of the thyroidal primary tumor in patients with papillary and follicular thyroid cancers has substantial ability to predict the behavior of subsequent deposits of metastatic and recurrent cancer with respect to iodine trapping and concentration. Our findings require confirmation in prospective studies to more accurately determine the predictive ability of the test and its role in the postoperative management of patients with DTC. If confirmed, NIS IS of DTC primary lesions may prove useful in the management of patients with known or suspected metastatic thyroid cancer.

Age-dependent cognitive deficits and neuronal apoptosis in cyclooxygenase-2 transgenic mice.

The cyclooxygenases catalyze the rate-limiting step in the formation of prostaglandins from arachidonic acid and are the pharmacological targets of (NSAIDs). In brain, cyclooxygenase-2 (COX-2), the inducible isoform of cyclooxygenase, is selectively expressed in neurons of the cerebral cortex, hippocampus, and amygdala. As an immediate-early gene, COX-2 is dramatically and transiently induced in these neurons in response to NMDA receptor activation. In models of acute excitotoxic neuronal injury, elevated and sustained levels of COX-2 have been shown to promote neuronal apoptosis, indicating that upregulated COX-2 activity is injurious to neurons. COX-2 may also contribute to the development of Alzheimer's disease, for which early administration of NSAIDs is protective against development of the disease. To test the effect of constitutively elevated neuronal COX-2, transgenic mice were generated that overexpressed COX-2 in neurons and produced elevated levels of prostaglandins in brain. In cross-sectional behavioral studies, COX-2 transgenic mice developed an age-dependent deficit in spatial memory at 12 and 20 months but not at 7 months and a deficit in aversive behavior at 20 months of age. These behavioral changes were associated with a parallel age-dependent increase in neuronal apoptosis occurring at 14 and 22 months but not at 8 months of age and astrocytic activation at 24 months of age. These findings suggest that neuronal COX-2 may contribute to the pathophysiology of age-related diseases such as Alzheimer's disease by promoting memory dysfunction, neuronal apoptosis, and astrocytic activation in an age-dependent manner.

Reactivity of site-isolated metal clusters: propylidyne on gamma-Al2O3-supported Ir4.

To contrast the reactivity of supported metal clusters with that of extended metal surfaces, we investigated the reactions of tetrairidium clusters supported on porous gamma-Al2O3 (Ir4/gamma-Al2O3) with propene and with H2. Infrared, 13C NMR, and extended X-ray absorption fine-structure spectroscopy were used to characterize the ligands formed on the clusters. Propene adsorption onto Ir4/gamma-Al2O3 at 298 K gave stable, cluster-bound mu3-propylidyne. Propene adsorbed onto Ir4/gamma-Al2O3 at 138 K reacted at approximately 219 K to form a stable, highly dehydrogenated, cluster-bound hydrocarbon species approximated as CxHy (such as, for example, C3H2 or C2H). H2 reacted with Ir4/gamma-Al2O3 at 298 K, forming ligands (likely hydrides), which prevented subsequent reaction of the clusters with propene to form propylidyne. Propylidyne on Ir4 was stable in helium or H2 as the sample was heated to 523 K, whereupon it reacted with oxygen of the support to give CO. Propylidyne on Ir4 did not undergo isotopic exchange in the presence of D2 at 298 K. In contrast, the literature shows that propylidyne chemisorbed on extended metal surfaces is hydrogenated in the presence of H2 (or D2) and exchanges hydrogen with gaseous D2 at room temperature; in the absence of H2, it decomposes thermally to give hydrocarbon fragments at temperatures much less than 523 K. The striking difference in reactivities of propylidyne on clusters and propylidyne on extended metal surfaces implies the requirement of ensembles of more than the three metal surface atoms bonded to propylidyne in the surface reactions. The results highlight the unique reactivity of small site-isolated metal clusters.

Analysis of Hurthle cell neoplasms of the thyroid by interphase fluorescence in situ hybridization.

Recent studies have indicated that numerical chromosomal abnormalities including changes in p53 and cyclin D1 may be involved in Hurthle cell tumorigenesis. We analyzed a series of Hurthle cell neoplasms of the thyroid to evaluate the diagnostic and prognostic utility of numerical anomalies by DNA fluorescent probes for cyclin D1 and p53 gene loci and chromosomes 5, 7, 11, 12, 17, and 22. Interphase fluorescence in situ hybridization (FISH) analysis was performed on paraffin-embedded tissue sections from 10 Hurthle cell adenomas, 19 Hurthle cell carcinomas, and 7 normal thyroid tissues used as controls. Directly labeled fluorescent DNA probes for the centromere region of chromosomes 7, 11, 12, and 17 and locus-specific probes for chromosomes 5 and 22, cyclin D1, and p53 were utilized for dual-probe hybridizations. Sixty percent (6 of 10) Hurthle cell adenomas and 63% (12 of 19) Hurthle cell carcinomas showed chromosome gains. Twenty percent (2 of 10) Hurthle cell adenomas and 26% (5 of 19) Hurthle cell carcinomas showed chromosome losses. Normal thyroid tissues used as controls showed no chromosomal abnormalities. Among Hurthle cell tumors with chromosomal abnormalities, adenomas averaged 2.7 gains and 0.3 losses per case, and carcinomas averaged 3.3 gains and 0.6 losses per case. The two adenomas with chromosome losses each showed loss of one chromosome, whereas the five carcinomas with losses averaged 1.8 losses per case. Chromosome 22 was the most common loss identified, occurring in three of the 11 patients who died of disease. These results indicate that chromosomal imbalances as gains are common in both benign and malignant Hurthle cell neoplasms, but Hurthle cell carcinomas tend to have more chromosome losses than adenomas. Among Hurthle cell carcinomas in this study, chromosome losses were identified only from patients who died of disease. The loss of chromosome 22 may have prognostic value in Hurthle cell carcinoma of the thyroid.

Expression of the sodium iodide symporter in human kidney.

BACKGROUND: The human sodium iodide symporter (hNIS) is a transmembrane protein that mediates the active transport of iodide in the thyroid gland. Following cloning of NIS, NIS expression has been detected in a broad range of nonthyroidal tissues, suggesting that iodide transport in these tissues is conferred by the expression of functional NIS protein. METHODS: The aim of this study was to examine functional hNIS expression in kidney by reverse transcription-polymerase chain reaction (RT-PCR), ribonuclease protection assay (RPA), immunohistochemistry, and Western blot analysis accompanied by iodide accumulation studies in kidney cells. RESULTS: Using a pair of full-length hNIS-specific oligonucleotide primers, RT-PCR followed by Southern hybridization revealed hNIS mRNA expression in normal human kidney tissue. The PCR products were subjected to automated sequencing and revealed full identity with the published human thyroid-derived NIS cDNA sequence. Furthermore, positive protected bands indicating the presence of hNIS mRNA were apparent in RPA gel lanes corresponding to human kidney cells as well as Chinese hamster ovary (CHO) cells stably transfected with hNIS cDNA and Graves' thyroid tissue. Immunohistochemical analysis of normal human kidney tissue using a mouse monoclonal hNIS-specific antibody showed marked hNIS-specific immunoreactivity confined to tubular cells, while no hNIS-specific immunoreactivity was detected in the glomeruli. NIS protein expression in human kidney cells was further confirmed by Western blot analysis. In addition, accumulation of (125)I was detected in human kidney cells in vitro and was shown to be sodium dependent and sensitive to perchlorate. CONCLUSIONS: Functional hNIS expression was demonstrated in the renal tubular system, suggesting that renal iodide transport may be, at least in part, an active process driven by NIS.

Nondiagnostic thyroid fine-needle aspiration cytology: management dilemmas.

Approximately 10% to 20% of thyroid biopsies by fine-needle aspiration (FNA) are nondiagnostic. The management of thyroid nodules in which FNA is nondiagnostic remains controversial because few studies have addressed this issue. We retrospectively reviewed the medical records of 153 patients with nondiagnostic FNAs of the thyroid performed in 1994. Sixty patients had reaspiration biopsies performed. Thirty-seven specimens (62%) were diagnostic and 23 (38%) remained nondiagnostic. Of the 27 patients who had a thyroid operation, 10 (37%) had a malignancy. Preoperative information about physical examination, ultrasound imaging, or nondiagnostic FNA did not predict outcome. Nondiagnostic FNAs of the thyroid may be associated with a high probability of thyroid malignancy. Nondiagnostic FNAs should not be considered benign. Reaspiration followed by selective surgical treatment is recommended.

FHIT and TSG101 in thyroid tumours: aberrant transcripts reflect rare abnormal RNA processing events of uncertain pathogenetic or clinical significance.

OBJECTIVE: The chromosomal regions containing the two putative tumour suppressors, fragile histidine triad gene (FHIT) and tumour suppressor gene 101 (TSG101), are deleted frequently in thyroid tumours. We therefore analysed FHIT and TSG101 transcripts in a group of advanced thyroid tumours to establish their role in thyroid tumorigenesis. DESIGN: Retrospective analysis of FHIT and TSG101 mRNA transcripts and genomic DNA from cryo-preserved thyroid tumours. TP53, previously shown at the genomic level not to be mutated in this cohort of tumours, served as a control. PATIENTS: We analysed nine follicular thyroid carcinomas (FTC), six papillary thyroid carcinomas and six follicular adenomas (FA) and histologically normal thyroid tissue from four of the FA patients. MEASUREMENTS: Single stage and nested reverse transcription polymerase chain reaction (RT-PCR) products of FHIT, TSG101, and TP53 were analysed by agarose or polyacrylamide gel electrophoresis and sequenced. Genomic DNA was also analysed by polymerase chain reaction and sequencing (FHIT) or by Southern blotting (TSG101). Clinical data were correlated with the results of the mutation analysis. RESULTS: Truncated FHIT transcripts were observed frequently alongside full length transcripts with nested RT-PCR, most often in FTC, while single stage RT-PCR revealed only normal length transcripts in all tumours. Similar results were obtained for TP53, while abnormal TSG101 transcripts were detectable by single stage RT-PCR. Sequence analysis of the truncated FHIT and TSG101 transcripts revealed mainly exon skipping and alternate RNA processing events. Only a single point mutation (of TSG101) was found. Southern blotting for the TSG101 gene, and PCR amplification and sequencing of the FHIT gene showed no evidence of genomic abnormalities in either case, and there was no evidence of splice site mutations in the FHIT gene, suggesting that the truncated transcripts result from altered RNA processing. There was no relationship between tumour stage, grade or survival and the presence of FHIT or TSG101 abnormalities. CONCLUSIONS: Truncated FHIT and TSG101 transcripts in thyroid tumours reflect alternate mRNA splicing events, rather than genomic deletions. Such abnormal RNA processing seems to be common and widespread in thyroid neoplasms, as similar results were obtained by analysis of transcripts of TP53, which we had previously shown not to be mutated in these specimens. Although a pathogenetic role for these aberrant transcripts remains possible, no correlation was found with stage, histological grade or outcome in this small group of advanced thyroid malignancies. Relaxation of mRNA splice control appears to be a feature of follicular cell-derived thyroid neoplasms.

Pathologic features, proliferative activity, and cyclin D1 expression in Hurthle cell neoplasms of the thyroid.

Making a histologic distinction between Hurthle cell adenomas and carcinomas sometimes may be difficult. We analyzed a series of Hurthle cell lesions to determine whether specific histologic features and expression of Ki67 and cyclin D1 could be useful in distinguishing Hurthle cell adenomas from carcinomas. Formalin-fixed, paraffin-embedded tissues from 128 Hurthle cell neoplasms, including 59 adenomas; 55 carcinomas; and 14 tumors classified as neoplasms of uncertain malignant behavior (UMB), which had equivocal capsular invasion but no vascular invasion, were analyzed for expression of Ki67 and cyclin D1 by immunostaining. The distribution of immunoreactivity for Ki67 with antibody MIB-1 was analyzed by quantifying the percentage of positive nuclei that was expressed as the labeling index. None of the patients with adenomas or UMB tumors developed recurrent or metastatic disease after a mean follow-up of 7.8 and 7.9 years, respectively. Of the 55 patients with Hurthle cell carcinoma, 19 were associated with metastatic disease, 13 of whom died with disease. No patient with a Hurthle cell carcinoma without vascular invasion developed metastatic disease. The mean tumor size for Hurthle cell carcinomas (4.8 cm) was significantly larger than that of Hurthle cell adenomas (3.1 cm) or UMB tumors (3.7 cm). No patient with a Hurthle cell tumor smaller than 3.5 cm developed metastatic disease, even when vascular invasion was present. The Ki67 labeling index in Hurthle cell carcinomas (10.0 +/- 1.2) was 3-fold higher than in Hurthle cell adenomas (3.2 +/- 0.3). The Ki67 labeling index in the UMB group was 5.0 +/- 0.7. Cyclin D1 showed diffuse nuclear staining in 1 of the 59 (1.7%) Hurthle cell adenomas, in 10 of the 55 (18%) Hurthle cell carcinomas, and in none of the UMB tumors. In summary, analyses of the cell cycle proteins Ki67 and cyclin D1 in Hurthle cell thyroid neoplasms indicate that these markers may assist in distinguishing some Hurthle cell carcinomas from adenomas. Among the Hurthle cell carcinomas, large tumor size and vascular invasion are associated with clinically aggressive tumors. Our study also suggests that Hurthle cell neoplasms with only equivocal capsular invasion and no vascular invasion should behave in a benign manner.

Intranuclear holes (cytoplasmic pseudoinclusions) in parathyroid neoplasms, or "holes happen".

BACKGROUND: A parathyroid adenoma demonstrating intranuclear holes on aspiration cytology prompted a review of parathyroid neoplasms to determine the frequency of this phenomenon. METHODS: Aspiration cytology slides from 30 parathyroid adenomas and 1 parathyroid carcinoma were reviewed. In addition, histologic slides from 136 parathyroid adenomas and 7 parathyroid carcinomas were reviewed. Twenty-two cases had both cytologic and histologic slides available for review. The presence and approximate frequency of intranuclear holes were recorded. RESULTS: On cytologic smears, intranuclear holes were found in 3 of the 31 cases reviewed (2 adenomas and 1 carcinoma). The holes were frequent in only one adenoma (the index case) and moderate-rare in the other two cases. Review of tissue slides showed holes in 9 of 136 adenomas and 3 of 7 carcinomas; 2 adenomas and 2 carcinomas had frequent holes, whereas the remainder had holes infrequently. CONCLUSIONS: Intranuclear holes do occur in parathyroid neoplasia, in rare cases with considerable frequency. When intranuclear holes are observed in aspiration cytology specimens from the thyroid region, various thyroid and parathyroid conditions must be considered.

Monoclonal antibodies against the human sodium iodide symporter: utility for immunocytochemistry of thyroid cancer.

The recent cloning of the thyroidal protein that is responsible for iodide transport, the sodium iodide symporter (hNIS), has made possible studies designed to characterize its structure, function and expression in thyroidal tissues. Using a mannose binding protein (MBP)-hNIS fusion protein as antigen, we have developed mouse monoclonal antibodies against hNIS to utilize as tools in such studies. Twenty-four clones were initially recovered which recognized the MBP-hNIS fusion protein, but only two of them were specific for hNIS while the others recognized MBP alone. Both antibodies were found to be immunoglobulin G (IgG) 1kappa (kappa). The specificity of antibodies was tested by Western blotting using membranes prepared from COS-7 cells transiently transfected with the pcDNA3 plasmid containing the full-length hNIS cDNA, or cells transfected with the pcDNA3 vector. A major band with a molecular weight (MW) of approximately 97 kDa, and several minor bands with MW of approximately 160 kDa, approximately 68 kDa, approximately 30 kDa and approximately 15 kDa, were detected specifically in the hNIS-transfected cells. After enzymatic deglycosylation, the major band was present at 68 kDa, as expected based upon the amino acid sequence of hNIS. Immunohistochemistry was performed with several different types of thyroid tissue and non-thyroidal tissues, using the monoclonal antibodies. Strong immunostaining was observed in Graves' tissue, with intermediate staining in papillary and follicular thyroid cancers and an absence of staining in Hürthle cell cancer. The staining was specific for the follicular epithelium and was concentrated in the basolateral portion of the cell membrane. These monoclonal hNIS antibodies should prove useful in the characterization of NIS expression in benign and malignant thyroid tissue and in studies characterizing its structure and function.

Impact of primary surgery on outcome in 300 patients with pathologic tumor-node-metastasis stage III papillary thyroid carcinoma treated at one institution from 1940 through 1989.

BACKGROUND: The pathologic tumor-node-metastasis (pTNM) system is universally used to define the extent of disease in human malignancies. This study evaluated the impact of initial therapy on cause-specific mortality (CSM) rates and recurrence rates in pTNM stage III papillary thyroid carcinoma. METHODS: Three hundred patients (median age, 58 years) were followed on average for 14 postoperative years. Of these, 246 patients (82%) had complete primary tumor resection; 208 patients (69%) had nodal metastases; 161 (54%) had locally invasive primary tumors; 45 patients (15%) underwent initial unilateral lobectomy (UL). Bilateral lobar resection (BLR) accounted for 242 patients (near-total, 54%; total thyroidectomy, 23%). RESULTS: The 30-year rates for CSM, distant metastases, nodal metastases, and local recurrence (LR) were 29%, 22%, 19%, and 16%, respectively. The 20-year rates for CSM were significantly higher (50% vs 14%) when primary tumor was incompletely resected (P = .0001). After complete resection, 20-year rates for CSM and LR after BLR were 12% and 10%, respectively, which were significantly lower (P < .05) than the 23% and 26% rates seen after UL. There were no significant differences in nodal metastases or distant metastases rates between UL and BLR (P > .4). The 20-year LR rate after total thyroidectomy (13%) was not different (P = .5) from the 11% seen after near-total thyroidectomy. CONCLUSIONS: In this nonrandomized evaluation of patients with pTNM stage III papillary thyroid carcinoma, the extent of primary thyroid resection appeared to significantly impact CSM and LR but did not apparently influence regional or distant metastasis.

Analysis of human sodium iodide symporter immunoreactivity in human exocrine glands.

The human sodium iodide symporter (hNIS) is an intrinsic transmembrane protein that mediates the active transport of iodide across the basolateral membrane of thyroid follicular cells. In addition to normally functioning thyroid tissue, various extrathyroidal tissues, including salivary gland, lacrimal gland, gastric mucosa, choroid plexus, and lactating mammary gland, have been demonstrated to accumulate iodide. After cloning and molecular characterization of the sodium iodide symporter, expression of hNIS messenger ribonucleic acid has been detected in a broad range of extrathyroidal tissues using Northern blot analysis and RT-PCR. In this study we used both monoclonal and polyclonal antibodies directed against different portions of hNIS protein together with a highly sensitive immunostaining technique to assess hNIS protein expression in tissue sections derived from normal human salivary and lacrimal glands, pancreas, as well as gastric and colonic mucosa. Immunohistochemical analysis of normal human salivary and lacrimal glands revealed marked hNIS immunoreactivity in ductal cells and less intense staining of acinar cells. Further, immunostaining of gastric and colonic mucosa showed marked hNIS immunoreactivity confined to chief and parietal cells in gastric mucosa and to epithelial cells lining mucosal crypts in colonic mucosa. In normal human pancreas, hNIS immunoreactivity was located in ductal cells, exocrine parenchymal cells, and Langerhans islet cells. In conclusion, our study demonstrates the expression of hNIS protein by several human exocrine glands, suggesting that iodide transport in these glands is a specific property conferred by the expression of hNIS protein, which may serve important functions by concentrating iodine in glandular secretions.

Development of monoclonal antibodies against the human sodium iodide symporter: immunohistochemical characterization of this protein in thyroid cells.

The thyroid sodium-iodide symporter (NIS) is responsible for iodide concentrating ability within thyroid follicular cells. We sought to develop monoclonal antibodies against human NIS (hNIS) for use as reagents in structure-function studies of the protein, as well as potential tools in the assessment of NIS expression in benign and malignant thyroid tissues. Synthetic peptides corresponding to the second ExMD and to the carboxy-terminal ExMD of hNIS were produced and utilized as antigens to develop monoclonal antibodies, which were tested by Western blotting using membranes prepared from COS-7 cells transiently transfected with a pcDNA3 plasmid containing the gene for the full-length hNIS, or a control vector. Western blotting showed a major band with molecular weight (MW) of approximately 97 kDa and several minor bands with MW of approximately 160 kDa, 68 kDa, 30 kDa, and 15 kDa, all specific for hNIS-transfected cells. Immunohistochemistry was performed in various types of thyroid tissues and nonthyroidal tissues, using the monoclonal antibodies. Strong immunostaining was observed in Graves' tissue, intermediate staining in papillary and follicular thyroid cancer, and no staining in Hürthle cell cancer or in nonthyroidal tissue. The staining was specific for the follicular epithelium in each of the tissues and was most intense in the basolateral portion of the cell membrane. Overall, our observations indicate that the monoclonal antibodies are specific for hNIS and will be invaluable reagents for investigating the role of NIS in thyroid disease.

Hyalinizing trabecular adenoma of the thyroid gland: recognition and characterization of its cytoplasmic yellow body.

Many round, pale yellow, cytoplasmic inclusion bodies were found in hematoxylin and eosin-stained sections of a hyalinizing trabecular adenoma of the thyroid. The bodies were refractile and frequently had a microvacuolated or granular substructure. They were usually located close to the nucleus, often indented it, and rarely occurred within it. Histochemically, they showed a glycosaminoglycan, proteoglycan, and lipid content, displayed autofluorescence on exposure to ultraviolet light, and were unreactive with a variety of immunostains. Ultrastructurally, the inclusions were consistent with giant lysosomes, showing parallel whorled and arrayed membranes ("fingerprint" bodies) as a component of their substructure. Review of sections of 75 hyalinizing trabecular adenomas in our files revealed that the cytoplasmic bodies were present in all cases (100%), indicating that these inclusions most likely are a universal feature of the neoplasm.

Direct extension of malignant lesions to the thyroid gland from adjacent organs: report of 17 cases.

OBJECTIVE: To characterize malignant tumors with direct extension to the thyroid gland from adjacent organs. METHODS: We retrospectively studied 17 patients with direct extension of malignant tumor to the thyroid from primary lesions in the head and neck who had been examined at Mayo Clinic Rochester between 1985 and 1994. The origin of the primary tumor was identified in all cases. Thyroid involvement was confirmed histologically. Data were analyzed for the frequency and types of malignant lesions, the clinical course, and the follow-up after thyroid involvement. RESULTS: All 17 study patients had a diagnosis of a primary malignant tumor before detection of thyroid involvement. Of the 17 patients, 12 had squamous cell carcinoma (SCC) of the larynx, 2 had SCC of the tongue base, 2 had SCC of the proximal and the cervical esophagus, respectively, and 1 had synovial cell sarcoma of the proximal esophagus. The time between diagnosis of the primary tumor and detection of thyroid invasion in the patients with SCC of the larynx or tongue base ranged from 1 to 196 months (mean, 38). Only 1 of these 14 patients had thyroid gland involvement clinically evident before surgical exploration. Thyroid invasion was diagnosed after surgical intervention. All three patients with esophageal malignant tumors had thyroid involvement clinically. CONCLUSION: SCC of the larynx, tongue base, or proximal esophagus may invade the thyroid gland directly. SCC of the larynx may have the greatest tendency to extend to the thyroid. In patients with SCC, extension of the primary malignant tumor to the thyroid gland should be considered despite lack of clinical evidence.

Unilateral total lobectomy: is it sufficient surgical treatment for patients with AMES low-risk papillary thyroid carcinoma?

BACKGROUND: Controversy continues regarding the optimal extent of primary thyroid resection in most patients with papillary thyroid carcinoma (PTC), who are at minimal risk of cause-specific mortality (CSM). This study was designed to compare CSM and recurrence rates after either unilateral lobectomy (UL) or bilateral lobar resection (BLR) in patients with PTC considered low risk by AMES criteria. METHODS: Outcome was studied in 1685 patients initially treated during 1940 through 1991 and followed for up to 54 postoperative years (mean, 18 years). One thousand six hundred fifty-six patients (98%) had complete primary tumor resection; 634 (38%) had involvement of regional nodes. One hundred ninety-five patients (12%) had UL; BLR accounted for 1468 (near-total 60%; total thyroidectomy 18%). RESULTS: Thirty-year rates for CSM and distant metastasis were 2% and 3%, respectively. Twenty-year rates for local recurrence and nodal metastasis were 4% and 8%, respectively. There were no significant differences in CSM or distant metastasis rates between UL and BLR (P > .2). After UL, 20-year rates for local recurrence and nodal metastasis were 14% and 19%, significantly higher (P = .0001) than the 2% and 6% rates seen after BLR. CONCLUSIONS: UL was not associated with higher CSM rates, but it was associated with a significantly higher risk of locoregional recurrence. Thus BLR probably represents a preferable initial surgical approach to patients with low-risk PTC.