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1. How Molecular and Ancillary Tests Can Help in Challenging Cytopathology Cases: Insights from the International Molecular Cytopathology Meeting

Author

Vigliar, Elena, primary, Bellevicine, Claudio, additional, Acanfora, Gennaro, additional, Morales, Allan Argueta, additional, Carillo, Anna Maria, additional, Cozzolino, Domenico, additional, Nacchio, Mariantonia, additional, Luca, Caterina De, additional, Pisapia, Pasquale, additional, Lozano, Maria D., additional, Roy-Chowdhuri, Sinchita, additional, and Troncone, Giancarlo, additional

Published
2024
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2. Spatially Resolved Molecular Approaches for the Characterisation of Non-Invasive Follicular Tumours with Papillary-like Features (NIFTPs)

Author

Piga, Isabella, primary, L’Imperio, Vincenzo, additional, Principi, Lucrezia, additional, Bellevicine, Claudio, additional, Fusco, Nicola, additional, Maffini, Fausto, additional, Venetis, Konstantinos, additional, Ivanova, Mariia, additional, Seminati, Davide, additional, Casati, Gabriele, additional, Pagani, Lisa, additional, Galimberti, Stefania, additional, Capitoli, Giulia, additional, Garancini, Mattia, additional, Gatti, Andrea-Valer, additional, Magni, Fulvio, additional, and Pagni, Fabio, additional

Published
2023
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3. Thyroid Cancer and Fibroblasts

Author

Avagliano, Angelica, primary, Fiume, Giuseppe, additional, Bellevicine, Claudio, additional, Troncone, Giancarlo, additional, Venuta, Alessandro, additional, Acampora, Vittoria, additional, De Lella, Sabrina, additional, Ruocco, Maria Rosaria, additional, Masone, Stefania, additional, Velotti, Nunzio, additional, Carotenuto, Pietro, additional, Mallardo, Massimo, additional, Caiazza, Carmen, additional, Montagnani, Stefania, additional, and Arcucci, Alessandro, additional

Published
2022
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4. Evaluation of the Molecular Landscape in PD-L1 Positive Metastatic NSCLC: Data from Campania, Italy

Author

Pisapia, Pasquale, primary, Iaccarino, Antonino, additional, De Luca, Caterina, additional, Acanfora, Gennaro, additional, Bellevicine, Claudio, additional, Bianco, Roberto, additional, Daniele, Bruno, additional, Ciampi, Luisa, additional, De Felice, Marco, additional, Fabozzi, Teresa, additional, Formisano, Luigi, additional, Giordano, Pasqualina, additional, Gridelli, Cesare, additional, Ianniello, Giovanni Pietro, additional, Libroia, Annamaria, additional, Maione, Paolo, additional, Nacchio, Mariantonia, additional, Pagni, Fabio, additional, Palmieri, Giovanna, additional, Pepe, Francesco, additional, Russo, Gianluca, additional, Salatiello, Maria, additional, Santaniello, Antonio, additional, Scamarcio, Rachele, additional, Seminati, Davide, additional, Troia, Michele, additional, Troncone, Giancarlo, additional, Vigliar, Elena, additional, and Malapelle, Umberto, additional

Published
2022
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5. Liquid Biopsy in Prostate Cancer Management—Current Challenges and Future Perspectives

Author

Crocetto, Felice, primary, Russo, Gianluca, additional, Di Zazzo, Erika, additional, Pisapia, Pasquale, additional, Mirto, Benito Fabio, additional, Palmieri, Alessandro, additional, Pepe, Francesco, additional, Bellevicine, Claudio, additional, Russo, Alessandro, additional, La Civita, Evelina, additional, Terracciano, Daniela, additional, Malapelle, Umberto, additional, Troncone, Giancarlo, additional, and Barone, Biagio, additional

Published
2022
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6. Evaluation of the Molecular Landscape in PD-L1 Positive Metastatic NSCLC: Data from Campania, Italy

Author

Pisapia, P, Iaccarino, A, De Luca, C, Acanfora, G, Bellevicine, C, Bianco, R, Daniele, B, Ciampi, L, De Felice, M, Fabozzi, T, Formisano, L, Giordano, P, Gridelli, C, Ianniello, G, Libroia, A, Maione, P, Nacchio, M, Pagni, F, Palmieri, G, Pepe, F, Russo, G, Salatiello, M, Santaniello, A, Scamarcio, R, Seminati, D, Troia, M, Troncone, G, Vigliar, E, Malapelle, U, Pisapia, Pasquale, Iaccarino, Antonino, De Luca, Caterina, Acanfora, Gennaro, Bellevicine, Claudio, Bianco, Roberto, Daniele, Bruno, Ciampi, Luisa, De Felice, Marco, Fabozzi, Teresa, Formisano, Luigi, Giordano, Pasqualina, Gridelli, Cesare, Ianniello, Giovanni Pietro, Libroia, Annamaria, Maione, Paolo, Nacchio, Mariantonia, Pagni, Fabio, Palmieri, Giovanna, Pepe, Francesco, Russo, Gianluca, Salatiello, Maria, Santaniello, Antonio, Scamarcio, Rachele, Seminati, Davide, Troia, Michele, Troncone, Giancarlo, Vigliar, Elena, Malapelle, Umberto, Pisapia, P, Iaccarino, A, De Luca, C, Acanfora, G, Bellevicine, C, Bianco, R, Daniele, B, Ciampi, L, De Felice, M, Fabozzi, T, Formisano, L, Giordano, P, Gridelli, C, Ianniello, G, Libroia, A, Maione, P, Nacchio, M, Pagni, F, Palmieri, G, Pepe, F, Russo, G, Salatiello, M, Santaniello, A, Scamarcio, R, Seminati, D, Troia, M, Troncone, G, Vigliar, E, Malapelle, U, Pisapia, Pasquale, Iaccarino, Antonino, De Luca, Caterina, Acanfora, Gennaro, Bellevicine, Claudio, Bianco, Roberto, Daniele, Bruno, Ciampi, Luisa, De Felice, Marco, Fabozzi, Teresa, Formisano, Luigi, Giordano, Pasqualina, Gridelli, Cesare, Ianniello, Giovanni Pietro, Libroia, Annamaria, Maione, Paolo, Nacchio, Mariantonia, Pagni, Fabio, Palmieri, Giovanna, Pepe, Francesco, Russo, Gianluca, Salatiello, Maria, Santaniello, Antonio, Scamarcio, Rachele, Seminati, Davide, Troia, Michele, Troncone, Giancarlo, Vigliar, Elena, and Malapelle, Umberto

Abstract

Background: Immune-checkpoint inhibitors (ICIs) have increased and improved the treatment options for patients with non-oncogene-addicted advanced stage non-small cell lung cancer (NSCLC). However, the role of ICIs in oncogene-addicted advanced stage NSCLC patients is still debated. In this study, in an attempt to fill in the informational gap on the effect of ICIs on other driver mutations, we set out to provide a molecular landscape of clinically relevant oncogenic drivers in programmed death-ligand 1 (PD-L1) positive NSCLC patients. Methods: We retrospectively reviewed data on 167 advanced stage NSCLC PD-L1 positive patients (≥1%) who were referred to our clinic for molecular evaluation of five driver oncogenes, namely, EGFR, KRAS, BRAF, ALK and ROS1. Results: Interestingly, n = 93 (55.7%) patients showed at least one genomic alteration within the tested genes. Furthermore, analyzing a subset of patients with PD-L1 tumor proportion score (TPS) ≥ 50% and concomitant gene alterations (n = 8), we found that n = 3 (37.5%) of these patients feature clinical benefit with ICIs administration, despite the presence of a concomitant KRAS gene alteration. Conclusions: In this study, we provide a molecular landscape of clinically relevant biomarkers in NSCLC PD-L1 positive patients, along with data evidencing the clinical benefit of ICIs in patient NSCLC PD-L1 positive alterations.

Published
2022

8. Combination of Lenvatinib and Pembrolizumab as Salvage Treatment for Paucicellular Variant of Anaplastic Thyroid Cancer: A Case Report

Author

Luongo, Cristina, primary, Porcelli, Tommaso, additional, Sessa, Francesca, additional, De Stefano, Maria Angela, additional, Scavuzzo, Francesco, additional, Damiano, Vincenzo, additional, Klain, Michele, additional, Bellevicine, Claudio, additional, Matano, Elide, additional, Troncone, Giancarlo, additional, Schlumberger, Martin, additional, and Salvatore, Domenico, additional

Published
2021
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10. BRCA1/2 NGS Somatic Testing in Clinical Practice: A Short Report

Author

Pepe, Francesco, primary, Pisapia, Pasquale, additional, Russo, Gianluca, additional, Nacchio, Mariantonia, additional, Pallante, Pierlorenzo, additional, Vigliar, Elena, additional, De Angelis, Carmine, additional, Insabato, Luigi, additional, Bellevicine, Claudio, additional, De Placido, Sabino, additional, Troncone, Giancarlo, additional, and Malapelle, Umberto, additional

Published
2021
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11. Evaluation of Micro Satellite Instability and Mismatch Repair Status in Different Solid Tumors: A Multicenter Analysis in a Real World Setting

Author

Malapelle, Umberto, primary, Parente, Paola, additional, Pepe, Francesco, additional, De Luca, Caterina, additional, Pisapia, Pasquale, additional, Sgariglia, Roberta, additional, Nacchio, Mariantonia, additional, Gragnano, Gianluca, additional, Russo, Gianluca, additional, Conticelli, Floriana, additional, Bellevicine, Claudio, additional, Vigliar, Elena, additional, Iaccarino, Antonino, additional, Covelli, Claudia, additional, Balistreri, Mariangela, additional, Clemente, Celeste, additional, Perrone, Giovanni, additional, Danza, Angela, additional, Scaramuzzi, Fabio, additional, Fassan, Matteo, additional, Troncone, Giancarlo, additional, and Graziano, Paolo, additional

Published
2021
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14. RNA-Based Assay for Next-Generation Sequencing of Clinically Relevant Gene Fusions in Non-Small Cell Lung Cancer

Author

De Luca, C, Pepe, F, Iaccarino, A, Pisapia, P, Righi, L, Listì, A, Greco, L, Gragnano, G, Campione, S, De Dominicis, G, Pagni, F, Sgariglia, R, Nacchio, M, Tufano, R, Conticelli, F, Vigliar, E, Bellevicine, C, Cortinovis, D, Novello, S, Molina-Vila, M, Rosell, R, Troncone, G, Malapelle, U, De Luca, Caterina, Pepe, Francesco, Iaccarino, Antonino, Pisapia, Pasquale, Righi, Luisella, Listì, Angela, Greco, Lorenza, Gragnano, Gianluca, Campione, Severo, De Dominicis, Gianfranco, Pagni, Fabio, Sgariglia, Roberta, Nacchio, Mariantonia, Tufano, Rossella, Conticelli, Floriana, Vigliar, Elena, Bellevicine, Claudio, Cortinovis, Diego Luigi, Novello, Silvia, Molina-Vila, Miguel Angel, Rosell, Rafael, Troncone, Giancarlo, Malapelle, Umberto, De Luca, C, Pepe, F, Iaccarino, A, Pisapia, P, Righi, L, Listì, A, Greco, L, Gragnano, G, Campione, S, De Dominicis, G, Pagni, F, Sgariglia, R, Nacchio, M, Tufano, R, Conticelli, F, Vigliar, E, Bellevicine, C, Cortinovis, D, Novello, S, Molina-Vila, M, Rosell, R, Troncone, G, Malapelle, U, De Luca, Caterina, Pepe, Francesco, Iaccarino, Antonino, Pisapia, Pasquale, Righi, Luisella, Listì, Angela, Greco, Lorenza, Gragnano, Gianluca, Campione, Severo, De Dominicis, Gianfranco, Pagni, Fabio, Sgariglia, Roberta, Nacchio, Mariantonia, Tufano, Rossella, Conticelli, Floriana, Vigliar, Elena, Bellevicine, Claudio, Cortinovis, Diego Luigi, Novello, Silvia, Molina-Vila, Miguel Angel, Rosell, Rafael, Troncone, Giancarlo, and Malapelle, Umberto

Abstract

Gene fusions represent novel predictive biomarkers for advanced non-small cell lung cancer (NSCLC). In this study, we validated a narrow NGS gene panel able to cover therapeutically-relevant gene fusions and splicing events in advanced-stage NSCLC patients. To this aim, we first assessed minimal complementary DNA (cDNA) input and the limit of detection (LoD) in different cell lines. Then, to evaluate the feasibility of applying our panel to routine clinical samples, we retrospectively selected archived lung adenocarcinoma histological and cytological (cell blocks) samples. Overall, our SiRe RNA fusion panel was able to detect all fusions and a splicing event harbored in a RNA pool diluted up to 2 ng/µL. It also successfully analyzed 46 (95.8%) out of 48 samples. Among these, 43 (93.5%) out of 46 samples reproduced the same results as those obtained with conventional techniques. Intriguingly, the three discordant results were confirmed by a CE-IVD automated real-time polymerase chain reaction (RT-PCR) analysis (Easy PGX platform, Diatech Pharmacogenetics, Jesi, Italy). Based on these findings, we conclude that our new SiRe RNA fusion panel is a valid and robust tool for the detection of clinically relevant gene fusions and splicing events in advanced NSCLC.

Published
2021

17. RNA-Based Assay for Next-Generation Sequencing of Clinically Relevant Gene Fusions in Non-Small Cell Lung Cancer

Author

De Luca, Caterina, primary, Pepe, Francesco, additional, Iaccarino, Antonino, additional, Pisapia, Pasquale, additional, Righi, Luisella, additional, Listì, Angela, additional, Greco, Lorenza, additional, Gragnano, Gianluca, additional, Campione, Severo, additional, De Dominicis, Gianfranco, additional, Pagni, Fabio, additional, Sgariglia, Roberta, additional, Nacchio, Mariantonia, additional, Tufano, Rossella, additional, Conticelli, Floriana, additional, Vigliar, Elena, additional, Bellevicine, Claudio, additional, Cortinovis, Diego Luigi, additional, Novello, Silvia, additional, Molina-Vila, Miguel Angel, additional, Rosell, Rafael, additional, Troncone, Giancarlo, additional, and Malapelle, Umberto, additional

Published
2021
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19. Development of a Stromal Microenvironment Experimental Model Containing Proto-Myofibroblast Like Cells and Analysis of Its Crosstalk with Melanoma Cells: A New Tool to Potentiate and Stabilize Tumor Suppressor Phenotype of Dermal Myofibroblasts

Author

Avagliano, Angelica, primary, Ruocco, Maria Rosaria, additional, Nasso, Rosarita, additional, Aliotta, Federica, additional, Sanità, Gennaro, additional, Iaccarino, Antonino, additional, Bellevicine, Claudio, additional, Calì, Gaetano, additional, Fiume, Giuseppe, additional, Masone, Stefania, additional, Masullo, Mariorosario, additional, Montagnani, Stefania, additional, and Arcucci, Alessandro, additional

Published
2019
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20. The Metallophosphoesterase-Domain-Containing Protein 2 (MPPED2) Gene Acts as Tumor Suppressor in Breast Cancer

Author

Pellecchia, Simona, primary, Sepe, Romina, additional, Federico, Antonella, additional, Cuomo, Mariella, additional, Credendino, Sara Carmela, additional, Pisapia, Pasquale, additional, Bellevicine, Claudio, additional, Nicolau-Neto, Pedro, additional, Severo Ramundo, Mariana, additional, Crescenzi, Elvira, additional, De Vita, Gabriella, additional, Terracciano, Luigi Maria, additional, Chiariotti, Lorenzo, additional, Fusco, Alfredo, additional, and Pallante, Pierlorenzo, additional

Published
2019
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21. Fine-Needle Aspiration Is Suitable for Breast Cancer BRCA Molecular Assessment: A Case Report

Author

Francesco Pepe, Pasquale Pisapia, Gianluca Russo, Mariantonia Nacchio, Elena Vigliar, Mario Giuliano, Umberto Malapelle, Giancarlo Troncone, Claudio Bellevicine, Pepe, Francesco, Pisapia, Pasquale, Russo, Gianluca, Nacchio, Mariantonia, Vigliar, Elena, Giuliano, Mario, Malapelle, Umberto, Troncone, Giancarlo, and Bellevicine, Claudio

Subjects
breast cancer, BRCA1/2, molecular cytopathology, FNA, PARPi, NGS, Pathology, RB1-214, skin and connective tissue diseases
Abstract

Breast cancer is the most common cause of cancer-related deaths in the female population worldwide. To the best of our knowledge, breast cancer (BRCA)1/2 gene mutations have not been described yet on breast cancer cytological specimens. Here we describe the case of a 38-year old woman with a family and personal history for breast cancer, who underwent a fine needle aspiration (FNA) procedure for a novel 30 mm lesion located in the external quadrants of the contralateral (left) breast. Cytological findings and ancillary immunostaining confirmed the diagnosis of a triple negative NST carcinoma. BRCA1/2 molecular assessment was carried out on DNA extracted from cytological (November 2020), biopsy (December 2014) and surgical resection (July 2015) specimens, as well as on the resection of a benign fibroadenoma, by using a next generation sequencing approach. Molecular analysis showed a pathogenic BRCA1 insertion (c.5266dupC; p.Q1756PfsTer74) in the cytological specimen (allelic fraction 92.0%), biopsy (allelic fraction 84.2%), surgical resection (allelic fraction 87.8%) and fibroadenoma (58.9%), demonstrating a germinal BRCA mutated status.

Published
2021
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22. Molecular Testing of Thyroid Fine-Needle Aspiration: Local Issues and Solutions. An Interventional Cytopathologist Perspective

Author

G. Troncone, Roberta Sgariglia, Francesco Pepe, Pasquale Pisapia, Mariantonia Nacchio, Caterina De Luca, Claudio Bellevicine, Bellevicine, Claudio, Sgariglia, Roberta, Nacchio, Mariantonia, De Luca, Caterina, Pisapia, Pasquale, Pepe, Francesco, and Troncone, Giancarlo

Subjects
Thyroid nodules, medicine.medical_specialty, 030209 endocrinology & metabolism, Prognostic stratification, thyroid, 03 medical and health sciences, 0302 clinical medicine, molecular pathology, medicine, Pathology, RB1-214, Medical physics, Thyroid.FNA, medicine.diagnostic_test, Molecular pathology, business.industry, Thyroid, medicine.disease, medicine.anatomical_structure, Fine-needle aspiration, FNA, 030220 oncology & carcinogenesis, NGS, business, molecular techniques, interventional cytopathologist
Abstract

Molecular testing has acquired a relevant role for diagnostic and prognostic stratification of indeterminate thyroid nodules. Besides the available commercial solutions marketed in the United States, various local testing strategies have been developed in the last decade. In this setting, the modern interventional cytopathologist, the physician who performs the both aspirate and the morphologic interpretation plays a key role in the correct handling of fine-needle aspiration (FNA) samples not only for microscopy but also for molecular techniques. This review summarizes experiences with local approaches to the molecular testing of thyroid FNA, highlighting the role of the modern interventional cytopathologist.

Published
2021

23. Cytopathology Practice in the COVID-19 Era: Focus on Sample Workload

Author

Umberto Malapelle, Giancarlo Troncone, Pasquale Pisapia, Caterina De Luca, Filippo Dello Iacovo, Antonino Iaccarino, Claudio Bellevicine, Elena Vigliar, Iaccarino, Antonino, Dello Iacovo, Filippo, Pisapia, Pasquale, De Luca, Caterina, Malapelle, Umberto, Bellevicine, Claudio, Troncone, Giancarlo, and Vigliar, Elena

Subjects
medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Outbreak, COVID-19, 030209 endocrinology & metabolism, Workload, Sample (statistics), 03 medical and health sciences, Biosafety, 0302 clinical medicine, cytopathology, Cytopathology, FNA, 030220 oncology & carcinogenesis, Pandemic, medicine, Pathology, cancer, RB1-214, Sampling (medicine), screening programs, Intensive care medicine, business
Abstract

Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak was declared a pandemic, the magnitude of coronavirus disease 2019 (COVID-19) has continued to grow, putting an unprecedented strain on all medical fields. Its effects on cytopathology workloads have been dramatic. Indeed, despite the implementation of several laboratory biosafety recommendations, cytological screening activities and cytological sampling of patients at low risk of malignancy have been postponed to limit the risk of contagion and to lessen the strain on overwhelmed hospital facilities. In this scenario, a drastic reduction in the total number of cytological specimens has been observed worldwide. This review summarizes the current evidence of the impact of the COVID-19 pandemic on cytopathology practice by focusing on its impact on cytological sample workload.

Published
2021

24. Evaluation of the Molecular Landscape in PD-L1 Positive Metastatic NSCLC: Data from Campania, Italy

Author

Pasquale Pisapia, Antonino Iaccarino, Caterina De Luca, Gennaro Acanfora, Claudio Bellevicine, Roberto Bianco, Bruno Daniele, Luisa Ciampi, Marco De Felice, Teresa Fabozzi, Luigi Formisano, Pasqualina Giordano, Cesare Gridelli, Giovanni Pietro Ianniello, Annamaria Libroia, Paolo Maione, Mariantonia Nacchio, Fabio Pagni, Giovanna Palmieri, Francesco Pepe, Gianluca Russo, Maria Salatiello, Antonio Santaniello, Rachele Scamarcio, Davide Seminati, Michele Troia, Giancarlo Troncone, Elena Vigliar, Umberto Malapelle, Pisapia, P, Iaccarino, A, De Luca, C, Acanfora, G, Bellevicine, C, Bianco, R, Daniele, B, Ciampi, L, De Felice, M, Fabozzi, T, Formisano, L, Giordano, P, Gridelli, C, Ianniello, G, Libroia, A, Maione, P, Nacchio, M, Pagni, F, Palmieri, G, Pepe, F, Russo, G, Salatiello, M, Santaniello, A, Scamarcio, R, Seminati, D, Troia, M, Troncone, G, Vigliar, E, Malapelle, U, Pisapia, Pasquale, Iaccarino, Antonino, DE LUCA, Caterina, Acanfora, Gennaro, Bellevicine, Claudio, Bianco, Roberto, Daniele, Bruno, Ciampi, Luisa, De Felice, Marco, Fabozzi, Teresa, Formisano, Luigi, Giordano, Pasqualina, Gridelli, Cesare, Pietro Ianniello, Giovanni, Libroia, Annamaria, Maione, Paolo, Nacchio, Mariantonia, Pagni, Fabio, Palmieri, Giovanna, Pepe, Francesco, Russo, Gianluca, Salatiello, Maria, Santaniello, Antonio, Scamarcio, Rachele, Seminati, Davide, Troia, Michele, Troncone, Giancarlo, Vigliar, Elena, and Malapelle, Umberto

Subjects
molecular oncology, molecular pathology, PD-L1, immune-checkpoint inhibitors, biomarkers, immune-checkpoint inhibitor, Lung Neoplasms, Organic Chemistry, General Medicine, Protein-Tyrosine Kinases, Catalysis, B7-H1 Antigen, Computer Science Applications, Inorganic Chemistry, Proto-Oncogene Proteins p21(ras), Carcinoma, Non-Small-Cell Lung, Proto-Oncogene Proteins, Mutation, Humans, biomarker, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, Retrospective Studies
Abstract

Background: Immune-checkpoint inhibitors (ICIs) have increased and improved the treatment options for patients with non-oncogene-addicted advanced stage non-small cell lung cancer (NSCLC). However, the role of ICIs in oncogene-addicted advanced stage NSCLC patients is still debated. In this study, in an attempt to fill in the informational gap on the effect of ICIs on other driver mutations, we set out to provide a molecular landscape of clinically relevant oncogenic drivers in programmed death-ligand 1 (PD-L1) positive NSCLC patients. Methods: We retrospectively reviewed data on 167 advanced stage NSCLC PD-L1 positive patients (≥1%) who were referred to our clinic for molecular evaluation of five driver oncogenes, namely, EGFR, KRAS, BRAF, ALK and ROS1. Results: Interestingly, n = 93 (55.7%) patients showed at least one genomic alteration within the tested genes. Furthermore, analyzing a subset of patients with PD-L1 tumor proportion score (TPS) ≥ 50% and concomitant gene alterations (n = 8), we found that n = 3 (37.5%) of these patients feature clinical benefit with ICIs administration, despite the presence of a concomitant KRAS gene alteration. Conclusions: In this study, we provide a molecular landscape of clinically relevant biomarkers in NSCLC PD-L1 positive patients, along with data evidencing the clinical benefit of ICIs in patient NSCLC PD-L1 positive alterations.

Published
2022

25. Thyroid Cancer and Fibroblasts

Author

Angelica Avagliano, Giuseppe Fiume, Claudio Bellevicine, Giancarlo Troncone, Alessandro Venuta, Vittoria Acampora, Sabrina De Lella, Maria Rosaria Ruocco, Stefania Masone, Nunzio Velotti, Pietro Carotenuto, Massimo Mallardo, Carmen Caiazza, Stefania Montagnani, Alessandro Arcucci, Avagliano, Angelica, Fiume, Giuseppe, Bellevicine, Claudio, Troncone, Giancarlo, Venuta, Alessandro, Acampora, Vittoria, De Lella, Sabrina, Ruocco, MARIA ROSARIA, Masone, Stefania, Velotti, Nunzio, Carotenuto, Pietro, Mallardo, Massimo, Caiazza, Carmen, Montagnani, Stefania, and Arcucci, Alessandro

Subjects
Cancer Research, thyroid cancer, tumor microenvironment, cancer-associated fibroblasts, thyroid cancer cells, Oncology
Abstract

Thyroid cancer is the most common type of endocrine cancer, and its prevalence continue to rise. Non-metastatic thyroid cancer patients are successfully treated. However, looking for new therapeutic strategies is of great importance for metastatic thyroid cancers that still lead to death. With respect to this, the tumor microenvironment (TME), which plays a key role in tumor progression, should be considered as a new promising therapeutic target to hamper thyroid cancer progression. Indeed, thyroid tumors consist of cancer cells and a heterogeneous and ever-changing niche, represented by the TME, which contributes to establishing most of the features of cancer cells. The TME consists of extracellular matrix (ECM) molecules, soluble factors, metabolites, blood and lymphatic tumor vessels and several stromal cell types that, by interacting with each other and with tumor cells, affect TME remodeling, cancer growth and progression. Among the thyroid TME components, cancer-associated fibroblasts (CAFs) have gained more attention in the last years. Indeed, recent important evidence showed that thyroid CAFs strongly sustain thyroid cancer growth and progression by producing soluble factors and ECM proteins, which, in turn, deeply affect thyroid cancer cell behavior and aggressiveness. Hence, in this article, we describe the thyroid TME, focusing on the desmoplastic stromal reaction, which is a powerful indicator of thyroid cancer progression and an invasive growth pattern. In addition, we discuss the origins and features of the thyroid CAFs, their influence on thyroid cancer growth and progression, their role in remodeling the ECM and their immune-modulating functions. We finally debate therapeutic perspectives targeting CAFs.

Published
2022
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26. The Metallophosphoesterase-Domain-Containing Protein 2 (MPPED2) Gene Acts as Tumor Suppressor in Breast Cancer

Author

Lorenzo Chiariotti, Simona Pellecchia, Romina Sepe, Mariana Severo Ramundo, Elvira Crescenzi, Pasquale Pisapia, Pierlorenzo Pallante, Gabriella De Vita, Claudio Bellevicine, Mariella Cuomo, Luigi Terracciano, Alfredo Fusco, Antonella Federico, Sara Carmela Credendino, Pedro Nicolau-Neto, Pellecchia, Simona, Sepe, Romina, Federico, Antonella, Cuomo, Mariella, Credendino, Sara Carmela, Pisapia, Pasquale, Bellevicine, Claudio, Nicolau-Neto, Pedro, Severo Ramundo, Mariana, Crescenzi, Elvira, De Vita, Gabriella, Terracciano, Luigi Maria, Chiariotti, Lorenzo, Fusco, Alfredo, and Pallante, Pierlorenzo

Subjects
0301 basic medicine, Cancer Research, MPPED2-AS1, tumor suppressor, Bisulfite sequencing, MPPED2, Biology, medicine.disease_cause, lcsh:RC254-282, breast cancer, long non-coding RNA, methylation, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Downregulation and upregulation, Carcinoma, medicine, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, DNA methylation, DNMT1, Cancer research, Breast carcinoma, Carcinogenesis
Abstract

Background: We have recently reported the downregulation of the Metallophosphoesterase-domain-containing protein 2 (MPPED2) gene and its cognate long non-coding RNA, MPPED2-AS1, in papillary thyroid carcinomas. Functional studies supported a tumor suppressor role of both these genes in thyroid carcinogenesis. We then decided to investigate their role in breast carcinogenesis. Methods: In order to verify MPPED2 expression, 45 human breast carcinoma samples have been investigated by quantitative real-time polymerase chain reaction (qRT-PCR). Then, MPPED2 has been transfected in several human breast carcinoma cell lines, analyzing its role in cell proliferation, migration and invasion. To study the regulation of MPPED2 expression the methylation of its promoter was investigated by targeted bisulfite sequencing. Results: MPPED2 expression was decreased in breast cancer samples, and this was confirmed by the analysis of data available in The Cancer Genome Atlas (TCGA). Interestingly, the hypermethylation of MPPED2 promoter likely accounted for its downregulation in breast cancer. Additionally, MPPED2-AS1 was also found downregulated in breast cancer tissues and, intriguingly, its expression decreased the hypermethylation of the MPPED2 promoter by inhibiting DNA methyltransferase 1 (DNMT1). Furthermore, the restoration of MPPED2 expression reduced cell proliferation, migration and invasion capability of breast carcinoma cell lines. Conclusion: Taken together, these results propose MPPED2 downregulation as a critical event in breast carcinogenesis.

Published
2019
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