Thyroid Diseases: Bombardieri E

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A digest of articles written 1999 and later, on the topic "Thyroid Diseases," originating from Planet Earth —» Bombardieri E.  Display:  All Citations ·  All Abstracts
1 Guideline Guidelines for radioiodine therapy of differentiated thyroid cancer. 2008

Luster M, Clarke SE, Dietlein M, Lassmann M, Lind P, Oyen WJ, Tennvall J, Bombardieri E, Anonymous00011. · Department of Nuclear Medicine, University of Würzburg, Josef-Schneider-Strasse 2, 97080 Würzburg, Germany. · Eur J Nucl Med Mol Imaging. · Pubmed #18670773 No free full text.

Abstract: INTRODUCTION: The purpose of the present guidelines on the radioiodine therapy (RAIT) of differentiated thyroid cancer (DTC) formulated by the European Association of Nuclear Medicine (EANM) Therapy Committee is to provide advice to nuclear medicine clinicians and other members of the DTC-treating community on how to ablate thyroid remnant or treat inoperable advanced DTC or both employing large 131-iodine ((131)I) activities. DISCUSSION: For this purpose, recommendations have been formulated based on recent literature and expert opinion regarding the rationale, indications and contraindications for these procedures, as well as the radioiodine activities and the administration and patient preparation techniques to be used. Recommendations also are provided on pre-RAIT history and examinations, patient counselling and precautions that should be associated with (131)I iodine ablation and treatment. Furthermore, potential side effects of radioiodine therapy and alternate or additional treatments to this modality are reviewed. Appendices furnish information on dosimetry and post-therapy scintigraphy.

2 Review MIBG for diagnosis and therapy of medullary thyroid carcinoma: is there still a role? free! 2008

Castellani MR, Seregni E, Maccauro M, Chiesa C, Aliberti G, Orunesu E, Bombardieri E. · Nuclear Medicine Division, Department of Diagnostic Imaging and Therapy, Istituto Nazionale Tumori IRCCS Foundation, Milan, Italy. · Q J Nucl Med Mol Imaging. · Pubmed #19088696 links to  free full text

Abstract: Medullary thyroid carcinoma (MTC) is a relatively rare neuroendocrine tumour originating from the parafollicular C cells and releases calcitonin (hCt), carcinoembryonic antigen (CEA) and occasionally other substances. In 20-30% of cases MTC presents a germline mutation of the RET proto-oncogene and occurs in 3 different hereditary forms: familial MTC, multiple endocrine neoplasia (MEN) 2A and MEN 2B syndrome. Prognosis of MTC is largely related to tumour extension at disease onset. Surgery remains the most effective therapy for potential cure. Overall survival is strictly linked to the occurrence of relapse. After surgery, serum hCt remains the most sensitive test for occult disease. Diagnostic imaging work-up includes ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), bone scintigraphy, as the more frequent sites of recurrence or metastases are cervical and mediastinal lymph nodes, lungs, liver and bone. Nuclear medicine procedures include (111)In-labelled somatostatin analogs, radioiodinated metaiodobenzylguanidine (MIBG), and several PET radiopharmaceuticals. Experience with radionuclide therapy in MTC is restricted to few patients treated with (131)I-MIBG or (90)Y-DOTATOC. Since 1987, 1 027 diagnostic MIBG scans were performed in the Department Department of Diagnostic Imaging and Therapy of the Istituto Nazionale Tumori IRCCS Foundation (Milan, Italy), 85 of which for MTC, with a sensitivity of 38.7% in patients with evidence of disease and 30.7 % if all patients were considered. Since 1994, 13 MTC patients were treated with MIBG with 4 partial responses and 4 stable diseases. Patients with liver or bone involvement responded to therapy and showed long-term partial remission of disease, others showed stability of disease, which was apparently unrelated to therapy. Improvement of efficacy can be achieved through dosimetric calculation of administered activity.

3 Review Position of nuclear medicine techniques in the diagnostic work-up of neuroendocrine tumors. free! 2004

Bombardieri E, Seregni E, Villano C, Chiti A, Bajetta E. · Nuclear Medicine Division, Istituto Nazionale Tumori, Milan, Italy. · Q J Nucl Med Mol Imaging. · Pubmed #15243410 links to  free full text

Abstract: In recent years nuclear medicine has contributed to the impressive development of the knowledge of neuroendocrine tumors in terms of biology (receptor scintigraphy), pharmacology (development of new tracers), and therapy (radiometabolic therapy). At present, it is impossible to plan the management of a patient affected by a neuroendocrine tumor without performing nuclear medicine examinations. The contribution of nuclear medicine had affected and improved the management of these patients by offering various important options that are part of the modern diagnosis and treatment protocols. The clinical experience and the literature confirm that, among the wide variety of tracers and nuclear medicine modalities available today, metaiodobenzylguanidine (MIBG) and DTPA-D-Phe-octreotide (pentetreotide) are the radiopharmaceuticals of current clinical use. Several new somatostatin analogues are under investigation. Positron emission tomography (PET) supplies a range of labelled compounds to be used for the visualization of tumor biochemistry. In addition to the first routinely used PET tracer in oncology, 18F-labelled deoxyglucose (FDG), a number of radiopharmaceuticals based on different precursors such as fluorodopamine and 5-hydroxytryptophan (5-HTP) are going to gain a clinical role. Of course, the diagnosis of neuroendocrine tumors has to be based on integrated information derived from different examinations including nuclear medicine studies. The clinical presentation of neuroendocrine tumors is highly variable: sometimes they manifest typical or atypical symptoms but they may also be detected by chance during an X-ray or ultrasound examination carried out for other reasons. At disease presentation nuclear medicine modalities are sometimes able to direct physicians towards the clinical diagnosis thanks to the specificity of their imaging mechanisms. They also play a role in disease staging and restaging, patient follow-up and treatment monitoring. In addition, the biological characterisation of neuroendocrine tissues (receptor status, glucose metabolism, differentiation, etc.) allows the interpretation of radiopharmaceutical uptake as a prognostic parameter and sometimes as a predictor of the response to treatment.

4 Review Diagnostic procedures in the follow-up of patients affected by MEN type 2. 2003

Seregni E, Pallotti F, Mattavelli F, Ferrari L, Martinetti A, Aliberti G, Villano C, Castellani MR, Bombardieri E. · Division of Nuclear Medicine, National Cancer Institute, Milan, Italy. · Tumori. · Pubmed #14870788 No free full text.

Abstract: Multiple endocrine neoplasia type 2 (MEN 2) is an inherited disease caused by germline mutations in the RET proto-oncogene. The most distinctive MEN 2 variants are MEN 2A, MEN 2B and familial medullary thyroid cancer (FMTC). The hallmark of these syndromes is the development of medullary thyroid carcinoma (MTC), which occurs in almost all patients with MEN 2 syndromes. Other endocrinopathies are variably expressed. Pheochromocytoma and hyperparathyroidism occur in patients with MEN 2A with a frequency of about 50% and 30%, respectively. In this paper we summarize the most relevant diagnostic methods to detect and monitor MTC, pheochromocytoma and hyperparathyroidism.

5 Review The role of radionuclide therapy in medullary thyroid cancer. 2003

Castellani MR, Alessi A, Savelli G, Bombardieri E. · Nuclear Medicine Division, National Cancer Institute, Milan, Italy. · Tumori. · Pubmed #14870787 No free full text.

Abstract: In medullary thyroid carcinoma (MTC) the detection of occult metastases is difficult and the prognosis of widespread disease is poor. In recent years several radiopharmaceuticals have become available for the diagnosis of this tumor. None of these tracers, however, has satisfactory diagnostic sensitivity and specificity. Furthermore, only few radiopharmaceutical compounds proved to have clinical value in therapeutic applications. Radionuclide therapy utilizes unsealed radioactive sources in order to deliver selective irradiation to the target organs or cancer lesions. This approach is only clinically indicated when there is a scintigraphic evidence of sufficient tumor uptake and a favorable biodistribution. When these conditions are present, radionuclide therapy can be adopted in MTC patients. Due to the low incidence of this tumor, the poor sensitivity of the available radiopharmaceuticals and their limited indications, the clinical experience in radionuclide therapy of MTC is still limited and there is general agreement among experts that it has only a palliative role. Here we briefly report the main experiences in radionuclide therapy in the past and in recent years. In addition, we summarize the results obtained with 131I-MIBG therapy at the Istituto Nazionale Tumori of Milan, as well as the most important ongoing preclinical and phase I/II trials.

6 Review Diagnostic and therapeutic aspects of iatrogenic hypoparathyroidism. 2003

Pallotti F, Seregni E, Ferrari L, Martinetti A, Biancolini D, Bombardieri E. · Nuclear Medicine Division, National Cancer Institute, Milan, Italy. · Tumori. · Pubmed #14870783 No free full text.

Abstract: Postsurgical hypoparathyroidism is the most common cause of chronic hypocalcemia. This condition may occur after removal of all parathyroid glands or after interruption of the blood supply to the parathyroid glands during thyroidectomy and radical neck dissection. The severity of the clinical presentation of hypocalcemia may vary from an asymptomatic laboratory finding to a severe life-threatening condition. Persistent hypoparathyroidism requires treatment that must be maintained throughout the patient's lifetime, and for this reason care is required to avoid complications. In this review the most relevant aspects of calcium homeostasis and its alteration in hypoparathyroidism are briefly discussed. In addition, the main approaches to treatment of the hypocalcemic state are presented.

7 Review FDG-PET in thyroid cancer. 2003

Crippa F, Alessi A, Gerali A, Bombardieri E. · Nuclear Medicine Division, PET Center, National Cancer Institute, Milan, Italy. · Tumori. · Pubmed #14870781 No free full text.

Abstract: The most widely used diagnostic nuclear medicine technique in well-differentiated thyroid cancer (DTC) is radioiodine scintigraphy, either diagnostic or post-therapeutic, together with serum thyroglobulin (Tg) measurement; this combination is usually able to determine the presence or absence of cancer. FDG-PET has shown less sensitivity in DTC that retains the ability to trap 131I. Several alternative procedures with single photon emitting radiopharmaceuticals have been evaluated including whole body scan with 201Tl, 99mTc-sestamibi or tetrofosmin scan, with different sensitivity and specificity. The main advantage of these tests is that their results are not influenced by the levels of TSH, therefore they do not require a hypothyroid state in the patient. Recently positron emission tomography (PET) with FDG has been demonstrated to be highly useful in thyroid cancer patients with a negative 131I whole body scan but measurable Tg. According to reports in the literature FDG-PET in the follow-up of operated patients has a sensitivity ranging from 70% to 90% in identifying the source of Tg. The demonstration of lesions can lead to a change in treatment including surgery or external radiation instead of radioiodine treatment. In Europe, medullary thyroid cancer (MTC) is currently visualized by 99mTc pentavalent dimercaptosuccinic acid (DMSA) and 99mTc-sestamibi or tetrofosmin. Metaiodobenzylguanidine (MIBG) radiolabeled with 123I or 131I is another reliable radiopharmaceutical for medullary tumors. (111)In-pentetreotide scan is positive in a high percentage of patients because MTC expresses somatostatin receptors. FDG-PET has an interesting role to play in calcitonin-positive patients, where PET has been shown to correctly identify lesions in cervical and mediastinal lymph nodes as well as at distant sites. Furthermore, calcitonin-guided PET has been found to be superior to CT and MRI in many patients. Recent reports indicated that 18F-DOPA scan in MTC seems to be more accurate than FDG-PET.

8 Review Recombinant human thyrotropin (rhTSH) in the follow-up and treatment of patients with thyroid cancer. 2003

Bombardieri E, Seregni E, Villano C, Aliberti G, Mattavelli F. · Nuclear Medicine Division, National Cancer Institute, Milan, Italy. · Tumori. · Pubmed #14870779 No free full text.

Abstract: The follow-up of thyroid cancer is based on the detection of residual and recurrent thyroid carcinoma. This is traditionally done by means of measurements of serum thyroglobulin (Tg) combined with various imaging techniques (131I-whole body scan, ultrasound and other modalities). Tg serum levels and the uptake of 131I on a whole body scan (WBS) depend on TSH stimulation, which in thyroidectomized patients can be obtained either by withdrawal of thyroid hormone treatment (thyroxine) or by administration of exogenous TSH. At present exogenous human TSH is obtained by means of recombinant DNA technology, (recombinant human TSH (rhTSH), Thyrogen). Even if the administration of rhTSH and withdrawal of thyroid hormone are not completely equivalent, the use of rhTSH has already entered the clinical routine (rhTSH Tg test and rhTSH WBS) because with rhTSH the morbidity and discomfort associated with the withdrawal of thyroid hormone can be avoided. At a recent International Consensus Conference on the follow-up of differentiated thyroid carcinoma it was proposed to carry out only Tg measurement after rhTSH stimulation; moreover, it was stated that 131I whole body scan has to be discouraged in patients submitted to radical surgery and radioiodine ablation with no clinical evidence of residual tumor and with undetectable levels of Tg during hormonal suppression of TSH. Similar strategies in this respect tend to eliminate the 131I WBS and propose only the rhTSH Tg test combined with head and neck ultrasound (US). This is still a matter of debate, also because it is not valid for all risk groups and not all patients undergo the same clinical management (radical surgery or not, thyroid ablation with 131I or not). However, the availability of rhTSH will definitely change the management of papillary and follicular thyroid carcinoma, also with regard to iodine treatment. In fact, rhTSH can be used during radioiodine treatment to enhance the 131I uptake by the cancer cells in particular groups of patients. Patients who could benefit from this approach can be divided into three subgroups: 1) patients in whom thyroxine withdrawal may be dangerous because of the effects of long-term TSH stimulation on the tumor mass (brain metastases, vertebral metastases, presence of neurological signs, heart diseases); 2) patients affected by tumors with marked biological aggressiveness and a low iodine uptake (variants of follicular carcinoma, insular carcinoma, tall and columnar cell variants of papillary thyroid carcinoma, Hürthle cell carcinoma); 3) patients with hypothalamic-pituitary alterations. The potential efficiency of rhTSH in radiometabolic treatment is an important issue that has been studied in a limited number of patients, but is worthy of further investigations in large perspective. A recent clinical prospective trial has been proposed by the Thyroid Cancer Study Group of the Istituto Nazionale Tumori and is now ongoing.

9 Review The biological characteristics of chromogranin A and its role as a circulating marker in neuroendocrine tumours. 1999

Ferrari L, Seregni E, Bajetta E, Martinetti A, Bombardieri E. · Nuclear Medicine Division, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy. · Anticancer Res. · Pubmed #10629629 No free full text.

Abstract: This paper reviews the biology of chromogranin A (CgA) and CgA-derived peptides and their possible role as markers for neuroendocrine tumours (NETs). NETs are neoplasms characterized by a low proliferation rate and, in some cases, a favourable prognosis. NETs often overproduce and release biologically active substances that are responsible for severe syndromes. The hormones and the biogenic amines released by biologically active NETs are currently used as biomarkers, but there is a need for sensitive markers for those NETs that are "biochemically silent". Circulating CgA levels have been demonstrated to be augmented in NET patients irrespective of the presence of syndromes related to hormone overproduction. Because of the high sensitivity and specificity of CgA, this glycoprotein can be successfully used in diagnosis, prognosis and follow-up of NETs. CgA blood evaluation seems of particular interest in the management of the gastroenteropancreatic tract NETs and in carcinoids.

10 Clinical Conference Comparative evaluation of two methods to assay thyroglobulin serum concentrations in patients with differentiated thyroid carcinomas. free! 2004

Ferrari L, Seregni E, Aliberti G, Martinetti A, Pallotti F, Villano C, Lucignani G, Bombardieri E. · Nuclear Medicine Division, Radioisotope Laboratory, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. · Q J Nucl Med Mol Imaging. · Pubmed #15499298 links to  free full text

Abstract: AIM: This study was aimed at the comparative assessment of the analytical and clinical performances of 2 tests for thyroglobulin (Tg) assays: the Dynotest Tg-Plus immunoradiometric assay (IRMA), a new method that might be of interest for its claimed superior sensitivity compared to other methods, and the HTGK-2 IRMA, one of the test currently used in clinical routine. METHODS: The study was performed in serum samples from 157 patients with differentiated thyroid carcinoma (DTC). The clinical sensitivity of the test was evaluated in patients with and without thyroid stimulating hormone (TSH) suppression. RESULTS: The lowest detectable Tg concentration values and the within-assay coefficient of variation (CV) were 0.4 and 0.8 microg/L and 5% and 3% for the Dynotest Tg-Plus assay and the HTGK-2 assay, respectively; the between-assay CV was 6% for both assays. The clinical results of the Dynotest Tg-Plus and those of the HTGK-2 kit were similar in both DTC patient populations, either under or off the TSH suppressive treatment. In spite of the manufacturer's statement that the calibrators of both assays had been standardized against the same common reference (standard CRM 457 of the Community Bureau of References), the Dynotest Tg-Plus test underrated by a factor of 0.5 the Tg values measured by means of HTGK-2 IRMA. CONCLUSION: The sensitivity of the Dynotest Tg-Plus IRMA appears to be similar to that of the HTGK-2 assay.

11 Article Role of surgery in treatment of advanced differentiated thyroid carcinomas. free! 2007

Mattavelli F, Bombardieri E, Collini P, Costa L, Pizzi N, Fallahadar D, Pennacchioli E, Santamaria S, Cascinelli N. · Otorhinolaryngology Unit, Istituto Nazionale dei Tumori, Milan. · Acta Otorhinolaryngol Ital. · Pubmed #17608132 links to  free full text

Abstract: Well-differentiated thyroid carcinomas are characterized by a long natural history. The evolution of the reconstructive techniques and the improvement of the peri-operative anaestesiologist management of the patient have contributed, over the last few years, to a progressive widening of demolitive surgery. The aims of enlarged surgical treatment in differentiated advanced thyroid carcinomas are to guarantee respiratory and alimentary functions as well as symptomatic benefits, to obtain local control of the disease and the recovery of adjuvant therapeutic options, such as metabolic and conventional radiation. In the present study, 27 patients who underwent enlarged surgery for differentiated thyroid carcinoma involving the superior digestive-aerial ways (SDAW) were treated between January 1992 and December 2002. The following results were achieved: Group 1 (7 patients): partial resection of the trachea and larynx: 57% of patients are Not Evidence Disease (NED) at a mean follow-up of 7 years; the other 43% are Alive With Disease (AWD). Group 2 (4 patients): total laryngectomy associated with emi-pharyngectomy or oesophagectomy of whom 50% are NED at a mean follow-up of 6 years. Group 3 (4 patients): mediastinum dissection in sternotomy of whom 3 patients NED at 7, 8 and 12 years of follow-up, respectively (75%). Group 4 (12 patients): latero-cervical, retro-clavear and subclavear dissection, of whom 75% of cases are NED at a mean follow-up of 5.1 years. Enlarged surgery is justified by the long natural history of the differentiated histotypes and the advantages it offers to adjuvant therapies. An essential principle, in the case of enlarged thyroid resections, is the modularity. With respect to the loco-regional spread of the disease, the surgeon has to study a treatment plan with a surgical procedure that involves the various elective districts of spreading, planning each surgical step with the entity of demolition and reconstruction being modulated according to the demand.

12 Article Thyroid-stimulating hormone suppression for protection against hypothyroidism due to craniospinal irradiation for childhood medulloblastoma/primitive neuroectodermal tumor. 2007

Massimino M, Gandola L, Collini P, Seregni E, Marchianò A, Serra A, Pignoli E, Spreafico F, Pallotti F, Terenziani M, Biassoni V, Bombardieri E, Fossati-Bellani F. · Department of Pediatrics, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. · Int J Radiat Oncol Biol Phys. · Pubmed #17601681 No free full text.

Abstract: PURPOSE: Hypothyroidism is one of the earliest endocrine effects of craniospinal irradiation (CSI). The effects of radiation also depend on circulating thyroid-stimulating hormone (TSH), which acts as an indicator of thyrocyte function and is the most sensitive marker of thyroid damage. Hence, our study was launched in 1998 to evaluate the protective effect of TSH suppression during CSI for medulloblastoma/primitive neuroectodermal tumor. PATIENTS AND METHODS: From Jan 1998 to Feb 2001, a total of 37 euthyroid children scheduled for CSI for medulloblastoma/primitive neuroectodermal tumor underwent thyroid ultrasound and free triiodothyronine (FT3), free thyroxine (FT4), and TSH evaluation at the beginning and end of CSI. From 14 days before and up to the end of CSI, patients were administered l-thyroxine at suppressive doses; every 3 days, TSH suppression was checked to ensure a value <0.3 mum/ml. During follow-up, blood tests and ultrasound were repeated after 1 year; primary hypothyroidism was considered an increased TSH level greater than normal range. CSI was done using a hyperfractionated accelerated technique with total doses ranging from 20.8-39 Gy; models were used to evaluate doses received by the thyroid bed. RESULTS: Of 37 patients, 25 were alive a median 7 years after CSI. They were well matched for all clinical features, except that eight children underwent adequate TSH suppression during CSI, whereas 17 did not. Hypothyroidism-free survival rates were 70% for the "adequately TSH-suppressed" group and 20% for the "inadequately TSH-suppressed" group (p = 0.02). CONCLUSIONS: Thyroid-stimulating hormone suppression with l-thyroxine had a protective effect on thyroid function at long-term follow-up. This is the first demonstration that transient endocrine suppression of thyroid activity may protect against radiation-induced functional damage.

13 Article Evaluation of circulating calcitonin: analytical aspects. 2003

Martinetti A, Seregni E, Ferrari L, Pallotti F, Aliberti G, Coliva A, Fracassi S, Bombardieri E. · Nuclear Medicine Division, National Cancer Institute, Milan, Italy. · Tumori. · Pubmed #14870789 No free full text.

Abstract: BACKGROUND AND AIM: Calcitonin (hCT) is a useful serum marker for the diagnosis and monitoring of medullary thyroid carcinoma (MTC). However, hCT values provided by different methods may differ, leading to difficulties in the interpretation of hCT results. In this study we compared four immunoradiometric (IRMA) and radioimmunometric (RIA) assays for hCT determination. MATERIAL AND METHODS: hCT was measured in 35 patients by means of the following commercially available IRMA or RIA kits: CT US (Biosource), IRMA hCT (Schering-CIS bio international), ultra-sensitive calcitonin (DSL), and calcitonin assay (Scantibodies). A comparison of the distribution of the hCT values measured by the tested IRMA-RIAs and a correlation analysis were performed. RESULTS: The hCT values were widely dispersed and the classification of the patients according to the hCT cutoff value varied depending on the assay used. CONCLUSION: Despite efforts to develop new, highly specific antibodies, the evaluation of this marker is still flawed by analytical inaccuracy. hCT values are widely dispersed depending on the method used for marker measurement; as a consequence, patient classification according to the hCT cutoff value is still dependent on the assay used.

14 Article Critical aspects of immunoradiometric thyroglobulin assays. 2003

Ferrari L, Biancolini D, Seregni E, Aliberti G, Martinetti A, Villano C, Pallotti F, Chiesa C, Bombardieri E. · Nuclear Medicine Division, National Cancer Institute, Milan, Italy. · Tumori. · Pubmed #14870780 No free full text.

Abstract: BACKGROUND AND AIM OF THE STUDY: Thyroglobulin (Tg) evaluation is currently used in the follow-up of patients with differentiated thyroid carcinoma (DTC), but the measurement methods are flawed by analytical inaccuracy. In this paper we describe the results of a comparison between seven different immunoradiometric assays (IRMAs) for Tg determination. MATERIAL AND METHODS: Tg was measured in 50 patients with DTC by means of the following commercially available IRMA kits: HTGK-2 (DiaSorin), Tg IRMA (Schering-CIS bio international), ELSA-hTG (Schering-CIS bio international), Tg IRMA C.T. (ICN Pharmaceuticals), SELco Tg (Medipan Diagnostica), Tg Bridge IRMA (Adaltis) and IRMA-mat Tg (BYK-Sangtec Diagnostica). The distribution of the Tg values measured by the different IRMAs was compared and a correlation analysis was performed. RESULTS: The Tg values were widely dispersed and the classification of patients according to Tg concentrations of clinical relevance varied depending on the IRMA used. CONCLUSION: Despite efforts to develop standardized Tg assays, the measurement of this biomarker is still affected by a considerable degree of analytical inaccuracy. Tg values vary widely between assays and the classification of patients according to Tg values with clinical relevance is still dependent on the assay used.

15 Article Differential expression of mucins 1-6 in papillary thyroid carcinoma: evidence for transformation-dependent post-translational modifications of MUC1 in situ. 2003

Magro G, Schiappacassi M, Perissinotto D, Corsaro A, Borghese C, Belfiore A, Colombatti A, Grasso S, Botti C, Bombardieri E, Perris R. · Institute for Anatomic Pathology, University of Catania, Via Biblioteca 4, Catania, Italy. · J Pathol. · Pubmed #12845632 No free full text.

Abstract: Mucins are primary glycoproteins of epithelia that are known to undergo major changes in their post-translational processing during neoplastic transformation. This study has examined the expression pattern of seven primary mucins, ie mucin (MUC) 1, 2, 3, 4, 5AC, 5B and 6, in normal, hyperplastic, benign neoplastic, and papillary-type carcinoma (PTC) tissues of the thyroid. MUC1 and MUC5B were the only mucins to be widely transcribed in both benign and malignant tissues. In contrast, MUC4 transcripts were undetectable in normal thyroids, and were present in only 40% of the hyperplastic and malignant thyroid tissues. In PTC, MUC1 was identified as a single mRNA transcript, rejecting the idea that this mucin may undergo transformation-dependent alternative splicing in thyroid tumours. The tissue distribution of MUC1 and MUC4 proteins was highly heterogeneous: this largely paralleled their mRNA expression profiles and supported the conclusion that whereas MUC1 was ubiquitously expressed in PTC, MUC4 was detectable in less than 20% of the cases analysed. In order to determine whether post-translational modifications of MUC1, putatively associated with malignancy, also occurred in the mucin produced by PTC, immunohistochemistry was performed with a panel of well-characterized anti-MUC1 antibodies in conjunction with digestion of the tissue sections with deglycosylating enzymes. These experiments, which were supported by immunochemical analyses of the MUC1 and MUC4 glycoforms extracted from tissues, collectively demonstrated markedly divergent MUC1 glycosylation profiles in normal and benign thyroid tissues when compared with PTC. Characteristically, these latter neoplastic cells produced mucin molecules carrying complex poly-N-lactosamine-type glycans capped with fucose and neuraminic acid residues. The present study also found evidence in PTC for the potential presence of proteolytically processed MUC1 isoforms which differ in their post-translational traits depending on whether they are retained on the cell surface or secreted into the extracellular space. It is proposed that the observed differences in the glycosylation properties of normal and neoplastic MUC1 may be exploitable as an ancillary tool in the diagnosis of PTC.

16 Article Predictive value of thyroglobulin changes for the efficacy of thyroid remnant ablation. 2001

Savelli G, Chiti A, Rodari M, Schreiner F, Maccauro M, Aliberti G, Gerali A, Bombardieri E. · Division of Nuclear Medicine, Istituto Nazionale Tumori, Milan, Italy. · Tumori. · Pubmed #11669557 No free full text.

Abstract: The aim of this case-control study was to determine the utility of the evaluation of changes in serum thyroglobulin (Tg) levels before and after 1311 diagnostic total body scan (TBS) in patients with thyroid cancer to predict the efficacy of radioiodine ablation. Among 134 consecutive patients with differentiated thyroid carcinoma (DTC) who had undergone a thyroidectomy and TBS prior to radioiodine ablation, we selected those subjects with no evidence of distant metastases and with two consecutive assessments of Tg before TBS and radioiodine ablation within a period of four weeks. With this selection procedure 27 patients (22 with papillary and five with follicular carcinomas) were included in our evaluation. The ablation therapy was considered successful when the TBS performed one year after treatment did not show any or less than 1% cervical 131I uptake, Tg levels remained below 3 ng/mL, and clinical and instrumental examinations were negative for the presence of relapses. These criteria divided the selected patients into two subsets: patients with successful radioiodine ablation and patients with residual thyroid tissue. The majority of patients with unsuccessful ablation showed an increase in serum Tg levels, while most of the patients with successful ablation showed a steady decrease in Tg concentrations. Statistical analysis evidenced that the increase in Tg levels after TBS was related to unsuccessful ablation (P > or = 0.01). By contrast, the rate of thyroid remnants with 131I uptake did not show any relationship with the outcome of ablation therapy. The group of patients with increasing Tg levels after TBS had a relative risk of 3.3 of unsuccessful ablative therapy compared to the group with stable or decreasing Tg levels. This study supports the concept that by monitoring Tg levels in patients who undergo diagnostic TBS before radioiodine ablation it is possible to obtain useful information about the efficacy of 131I therapy.