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Kelleher F.C.,Peter MacCallum Cancer Center | Kelleher F.C.,IE University | O'Sullivan H.,IE University | Smyth E.,The Royal Marsden Hospital | And 3 more authors.
Carcinogenesis | Year: 2013

Fibroblast growth factors (FGF) are a family of ligands that bind to four different types of cell surface receptor entitled, FGFR1, FGFR2, FGFR3 and FGFR4. These receptors differ in their ligand binding affinity and tissue distribution. The prototypical receptor structure is that of an extracellular region comprising three immunoglobulin (Ig)-like domains, a hydrophobic transmembrane segment and a split intracellular tyrosine kinase domain. Alternative gene splicing affecting the extracellular third Ig loop also creates different receptor isoforms entitled FGFRIIIb and FGFRIIIc. Somatic fibroblast growth factor receptor (FGFR) mutations are implicated in different types of cancer and germline FGFR mutations occur in developmental syndromes particularly those in which craniosynostosis is a feature. The mutations found in both conditions are often identical. Many somatic FGFR mutations in cancer are gain-of-function mutations of established preclinical oncogenic potential. Gene amplification can also occur with 19-22% of squamous cell lung cancers for example having amplification of FGFR1. Ontologic comparators can be informative such as aberrant spermatogenesis being implicated in both spermatocytic seminomas and Apert syndrome. The former arises from somatic FGFR3 mutations and Apert syndrome arises from germline FGFR2 mutations. Finally, therapeutics directed at inhibiting the FGF/FGFR interaction are a promising subject for clinical trials. © The Author 2013. Published by Oxford University Press.


Bartolazzi A.,Karolinska Hospital | Bartolazzi A.,St Andrea University Hospital | Sciacchitano S.,St Andrea University Hospital | Sciacchitano S.,St Pietro Fatebenefratelli Hospital Research Center
Applied Immunohistochemistry and Molecular Morphology | Year: 2012

In the last decade, the β-galactosyl binding protein galectin-3 has been the object of extensive molecular, structural, and functional studies aimed to clarify its biological role in cancer. Multicenter studies also contributed to discover the potential clinical value of galectin-3 expression analysis in distinguishing, preoperatively, benign from malignant thyroid nodules. As a consequence galectin-3 is receiving significant attention as tumor marker for thyroid cancer diagnosis, but some conflicting results mostly owing to methodological problems have been published. The possibility to apply preoperatively a reliable galectin-3 test method on fine needle aspiration biopsy (FNA)-derived thyroid cells represents an important achievement. When correctly applied, the method reduces consistently the gray area of thyroid FNA cytology, contributing to avoid unnecessary thyroid surgery. Although the efficacy and reliability of the galectin-3 test method have been extensively proved in several studies, its translation in the clinical setting requires well-standardized reagents and procedures. After a decade of experimental work on galectin-3-related basic and translational research projects, the major methodological problems that may potentially impair the diagnostic performance of galectin-3 immunotargeting are highlighted and discussed in detail. A standardized protocol for a reliable galectin-3 expression analysis is finally provided. The aim of this contribution is to improve the clinical management of patients with thyroid nodules, promoting the preoperative use of a reliable galectin-3 test method as ancillary technique to conventional thyroid FNA cytology. The final goal is to decrease unnecessary thyroid surgery and its related social costs. © 2011 by Lippincott Williams & Wilkins.


Carpi A.,University of Pisa | Rossi G.,CNR Institute of Neuroscience | Coscio G.D.,University of Pisa | Iervasi G.,CNR Institute of Neuroscience | And 5 more authors.
Annals of Medicine | Year: 2010

Background. New techniques of improving diagnostic reliability of thyroid nodules are needed. Aim and methods. This prospective cohort study includes patients with one (201) or multiple (22) palpable nodule(s). Preoperative fine-needle aspiration biopsy (FNAB), large-needle aspiration biopsy (LNAB), and galectin-3 detection on LNAB (GAL-3-LNAB) (total of 245 nodules) were compared when the FNAB finding was 'inadequate' or 'indeterminate'. The sizes of the needles used for FNAB and LNAB were compared with the size of thyroid follicles. Forty nodules were surgically excised according to current recommendation. Results. GAL-3-LNAB was inadequate in 4% of nodules, compared with 34% using FNAB and 11% using LNAB (P < 0.0001). GAL-3-LNAB showed no indeterminate findings, compared with 15% using FNAB and 13% using LNAB (P < 0.0001). Among the 40 excised nodules, GAL-3-LNAB showed the highest accuracy values. The sensitivity (P 0.011) and specificity (P < 0.000; P 0.001) ranges were 40%100% and 20%40% for FNAB, 40%100% and 50%53.7% for LNAB, and 100% and 76.7%80% for GAL-3-LNAB, respectively. The largest needles used for LNAB, 20 or 18 gauge, with an internal diameter of 0.6 or 0.91 mm, recorded the lowest rate of inadequate or indeterminate FNAB findings. Conclusions. GAL-3-LNAB reduced inadequate, abolished indeterminate findings, and provided specificity values higher than FNAB or LNAB in palpable thyroid nodules. © Informa UK Ltd.


Pennazza G.,Biomedical University of Rome | Santonico M.,University of Rome Tor Vergata | Martinelli E.,University of Rome Tor Vergata | Paolesse R.,University of Rome Tor Vergata | And 6 more authors.
Sensors and Actuators, B: Chemical | Year: 2011

The analysis of the volatile organic compounds (VOCs) released by bio-systems represents a promising approach for the diagnosis of human diseases including cancers. Experimental results suggested the possibility to detect tumors in vivo through the analysis of released VOCs from different body compartments, such as breath and skin. This paper illustrates the results obtained measuring VOCs mixtures released by well-characterized tumor cells derived from human malignancies by using an array of broadly selective chemical sensors. The patterns of VOCs emitted by two different melanoma tumorigenic cell lines transplanted ad hoc in a mice model were investigated. The recorded sensors signals are compatible with the existence of a distinguishable tumor specific pattern of VOCs evolving during the exponential phase of tumor growth. © 2010 Elsevier B.V. All rights reserved.


Bartolazzi A.,St Andrea University Hospital | Santonico M.,University of Rome Tor Vergata | Pennazza G.,Biomedical University of Rome | Martinelli E.,University of Rome Tor Vergata | And 3 more authors.
Sensors and Actuators, B: Chemical | Year: 2010

In recent years a body of evidences about the relationship between volatile compounds released in body compartments and diseases have been provided. These researches did not indicate if anomalous volatile patterns are a consequence of a general alteration of body metabolism or if they originate from cancer cells. In order to approach a solution to this question, in this paper, an experiment aimed at discriminating cultured tumoral cells lines from their volatile compounds is illustrated. Volatile organic compounds have been fingerprinted with a gas sensor array and a gas-chromatography/mass-spectrometer. These results suggest that cell lines from human tumors are characterized by a distinct volatile compounds profile and that these patterns when fingerprinted by a chemical sensor array tend to cluster according to the kind of tumor. These findings provide a hint about the possibility to identify a specific volatile fingerprint for each tumor type. © 2009 Elsevier B.V. All rights reserved.


Sciacchitano S.,University of Rome La Sapienza | Sciacchitano S.,Fondazione University Niccolo Cusano per la Ricerca Medico Scientifica | Lavra L.,Fondazione University Niccolo Cusano per la Ricerca Medico Scientifica | Ulivieri A.,Fondazione University Niccolo Cusano per la Ricerca Medico Scientifica | And 10 more authors.
Endocrine | Year: 2015

The use of galectin-3 ThyroTest in the preoperative evaluation of cytologically indeterminate (Thy-3) thyroid nodules has been largely validated by retrospective and prospective multicentre studies. Here we report the results of galectin-3 ThyroTest routinely applied in the management of Thy-3 nodules in combination with clinical and ultrasonography (US) examination, in which galectin-3 positive nodules were directly referred to surgery whereas galectin-3 negative lesions were considered for clinical and US long-term follow-up. A cohort of 331 patients, bearing 340 thyroid Thy-3 nodules, was enrolled and subjected to galectin-3 expression analysis. A total of 256 galectin-3 negative nodules were directed to periodical clinical and US examination, while 84 galectin-3 positive cases were referred to surgery. Excluding 63 dropout patients plus 15 patients that were operated because of clinical reasons the remaining 176 galectin-3 negative nodules were followed with clinical and US examination for an average period of 31 months. During the follow-up, the volume of galectin-3 negative nodules was unchanged in 85 cases (48 %), reduced in 47 (27 %), and increased in 44 (25 %). Based on combined clinical features and US follow-up results, a total of 36 out of 191 galectin-3 negative nodules (19 %) were referred to surgery, with a final histological finding of 28 benign lesions, three follicular tumor of uncertain malignant potential (FT-UMP), and five malignant lesions, corresponding to a 7 % false negative rate. In the group of 84 galectin-3 positive nodules, we detected 65 thyroid cancers with a prevalence of 77 %, 12 FT-UMPs, and 7 false positive lesions, corresponding to a 4 % false positive rate. A total of 150 patients were not operated and are still under clinical and US monitoring while surgery was performed in 118 patients with a final 70 thyroid cancers diagnosed, corresponding to a 59 % prevalence of malignancy detected at surgery and to a 26 % prevalence of malignancy among the entire Thy-3 nodule population. Galectin-3 ThyroTest is an easy and cheap diagnostic procedure that integrates conventional fine-needle-aspiration cytology, reduces the number of unnecessary thyroidectomies and increases the rate of malignancy at surgery. Clinical and US follow-up of galectin-3 negative lesions allows to further reduce false negative cases. © 2015 Springer Science+Business Media New York


Kelleher F.C.,Peter Mac Callum Cancer Center | Kelleher F.C.,St Vincents University Hospital | Viterbo A.,St Vincents University Hospital | Viterbo A.,St Andrea University Hospital
Cancers | Year: 2013

Undifferentiated pleomorphic sarcoma (UPS) is an inclusive term used for sarcomas that defy formal sub-classification. The frequency with which this diagnosis is assigned has decreased in the last twenty years. This is because when implemented, careful histologic assessment, immunohistochemistry, and ultra-structural evaluation can often determine lineage of differentiation. Further attrition in the diagnostic frequency of UPS may arise by using array-comparative genomic hybridization. Gene expression arrays are also of potential use as they permit hierarchical gene clustering. Appraisal of the literature is difficult due to a historical perspective in which specific molecular diagnostic methods were previously unavailable. The American Joint Committee on Cancer (AJCC) classification has changed with different inclusion criteria. Taxonomy challenges also exist with the older term "malignant fibrous histiocytoma" being replaced by "UPS". In 2010 an analysis of multiple sarcoma expression databases using a 170-gene predictor, re-classified most MFH and "not-otherwise-specified" (NOS) tumors as liposarcomas, leiomyosarcomas or fibrosarcomas. Interestingly, some of the classifier genes are potential molecular therapeutic targets including Insulin-like growth factor 1 (IGF-1), Peroxisome proliferator- activated receptor γ (PPARγ), Nerve growth factor β (NGF β) and Fibroblast growth factor receptor (FGFR). © 2013 by the authors; licensee MDPI, Basel, Switzerland.


D'Angelo F.A.,St Andrea University Hospital | Magistri P.,St Andrea University Hospital | Antolino L.,St Andrea University Hospital | Socciarelli F.,St Andrea University Hospital
International Journal of Surgical Pathology | Year: 2014

Metastases of non-thyroid malignancies to the thyroid gland have been reported in 1.4% to 3% of patients undergoing thyroid surgery for thyroid malignancy. We report a case of thyroid metastases from renal cell carcinoma in a 57-year-old man, who underwent a left nephrectomy 11 years earlier for a renal cell carcinoma. The histological examination demonstrated a CD-10 positive and thyroglobulin and thyroid transcription factor-1 negative tissue, with numerous noncaseating gigantocellular granulomas. These findings are interesting for the possible role of the immune response in metastatic localizations. © The Author(s) 2013.


PubMed | University of Rome La Sapienza, Fondazione University Niccolo Cusano per la Ricerca Medico Scientifica, Messina University and St Andrea University Hospital
Type: Journal Article | Journal: Endocrine | Year: 2016

The use of galectin-3 ThyroTest in the preoperative evaluation of cytologically indeterminate (Thy-3) thyroid nodules has been largely validated by retrospective and prospective multicentre studies. Here we report the results of galectin-3 ThyroTest routinely applied in the management of Thy-3 nodules in combination with clinical and ultrasonography (US) examination, in which galectin-3 positive nodules were directly referred to surgery whereas galectin-3 negative lesions were considered for clinical and US long-term follow-up. A cohort of 331 patients, bearing 340 thyroid Thy-3 nodules, was enrolled and subjected to galectin-3 expression analysis. A total of 256 galectin-3 negative nodules were directed to periodical clinical and US examination, while 84 galectin-3 positive cases were referred to surgery. Excluding 63 dropout patients plus 15 patients that were operated because of clinical reasons the remaining 176 galectin-3 negative nodules were followed with clinical and US examination for an average period of 31months. During the follow-up, the volume of galectin-3 negative nodules was unchanged in 85 cases (48%), reduced in 47 (27%), and increased in 44 (25%). Based on combined clinical features and US follow-up results, a total of 36 out of 191 galectin-3 negative nodules (19%) were referred to surgery, with a final histological finding of 28 benign lesions, three follicular tumor of uncertain malignant potential (FT-UMP), and five malignant lesions, corresponding to a 7% false negative rate. In the group of 84 galectin-3 positive nodules, we detected 65 thyroid cancers with a prevalence of 77%, 12 FT-UMPs, and 7 false positive lesions, corresponding to a 4% false positive rate. A total of 150 patients were not operated and are still under clinical and US monitoring while surgery was performed in 118 patients with a final 70 thyroid cancers diagnosed, corresponding to a 59% prevalence of malignancy detected at surgery and to a 26% prevalence of malignancy among the entire Thy-3 nodule population. Galectin-3 ThyroTest is an easy and cheap diagnostic procedure that integrates conventional fine-needle-aspiration cytology, reduces the number of unnecessary thyroidectomies and increases the rate of malignancy at surgery. Clinical and US follow-up of galectin-3 negative lesions allows to further reduce false negative cases.


PubMed | St Andrea University Hospital
Type: Case Reports | Journal: International journal of surgical pathology | Year: 2014

Metastases of non-thyroid malignancies to the thyroid gland have been reported in 1.4% to 3% of patients undergoing thyroid surgery for thyroid malignancy. We report a case of thyroid metastases from renal cell carcinoma in a 57-year-old man, who underwent a left nephrectomy 11 years earlier for a renal cell carcinoma. The histological examination demonstrated a CD-10 positive and thyroglobulin and thyroid transcription factor-1 negative tissue, with numerous noncaseating gigantocellular granulomas. These findings are interesting for the possible role of the immune response in metastatic localizations.

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