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3. miRNA–221 and miRNA–483–3p Dysregulation in Esophageal Adenocarcinoma

Author

Bozzarelli, Isotta, primary, Orsini, Arianna, additional, Isidori, Federica, additional, Mastracci, Luca, additional, Malvi, Deborah, additional, Lugaresi, Marialuisa, additional, Fittipaldi, Silvia, additional, Gozzellino, Livia, additional, Astolfi, Annalisa, additional, Räsänen, Jari, additional, D’Errico, Antonia, additional, Rosati, Riccardo, additional, Fiocca, Roberto, additional, Seri, Marco, additional, Krishnadath, Kausilia K., additional, Bonora, Elena, additional, and Mattioli, Sandro, additional

Published
2024
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4. miRNA-221 and miRNA-483-3p Dysregulation Correlated with Poor Survival in Esophageal Adenocarcinoma

Author

Bozzarelli, Isotta, primary, Isidori, Federica, additional, Orsini, Arianna, additional, Mastracci, Luca, additional, Malvi, Deborah, additional, Lugaresi, Marialuisa, additional, Fittipaldi, Silvia, additional, Soderstrom, Henna, additional, Räsänen, Jari, additional, D'Errico, Antonietta, additional, Tomezzoli, Anna, additional, Rosati, Riccardo, additional, Fiocca, Roberto, additional, Seri, Marco, additional, Krishnadath, Kausilia Krishnawatie, additional, Bonora, Elena, additional, and Mattioli, Sandro, additional

Published
2023
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8. Distribution of lymph node metastases in esophageal carcinoma [TIGER study]: study protocol of a multinational observational study

Author

Hagens, Eliza R. C., van Berge Henegouwen, Mark I., van Sandick, Johanna W., Cuesta, Miguel A., van der Peet, Donald L., Heisterkamp, Joos, Nieuwenhuijzen, Grard A. P., Rosman, Camiel, Scheepers, Joris J. G., Sosef, Meindert N., van Hillegersberg, Richard, Lagarde, Sjoerd M., Nilsson, Magnus, Räsänen, Jari, Nafteux, Philippe, Pattyn, Piet, Hölscher, Arnulf H., Schröder, Wolfgang, Schneider, Paul M., Mariette, Christophe, Castoro, Carlo, Bonavina, Luigi, Rosati, Riccardo, de Manzoni, Giovanni, Mattioli, Sandro, Garcia, Josep Roig, Pera, Manuel, Griffin, Michael, Wilkerson, Paul, Chaudry, M. Asif, Sgromo, Bruno, Tucker, Olga, Cheong, Edward, Moorthy, Krishna, Walsh, Thomas N., Reynolds, John, Tachimori, Yuji, Inoue, Haruhiro, Matsubara, Hisahiro, Kosugi, Shin-ichi, Chen, Haiquan, Law, Simon Y. K., Pramesh, C. S., Puntambekar, Shailesh P., Murthy, Sudish, Linden, Philip, Hofstetter, Wayne L., Kuppusamy, Madhan K., Shen, K. Robert, Darling, Gail E., Sabino, Flávio D., Grimminger, Peter P., Meijer, Sybren L., Bergman, Jacques J. G. H. M., Hulshof, Maarten C. C. M., van Laarhoven, Hanneke W. M., Mearadji, Banafsche, Bennink, Roel J., Annema, Jouke T., Dijkgraaf, Marcel G. W., and Gisbertz, Suzanne S.

Published
2019
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9. Correlations between molecular alterations, histopathological characteristics, and poor prognosis in esophageal adenocarcinoma

Author

Orsini, Arianna, Mastracci, Luca, Bozzarelli, Isotta, Ferrari, Anna, Isidori, Federica, Fiocca, Roberto, Lugaresi, Marialuisa, D’Errico, Antonietta, Malvi, Deborah, Cataldi-Stagetti, Erica, Spaggiari, Paola, Tomezzoli, Anna, Albarello, Luca, Ristimäki, Ari, Bottiglieri, Luca, Krishnadath, Kausilia K., Rosati, Riccardo, Romario, Uberto Fumagalli, Manzoni, Giovanni De, Räsänen, Jari, Martinelli, Giovanni, Mattioli, Sandro, Bonora, Elena, Consortium, on behalf of the EACSGE Consortium on behalf of the EACSGE, EACSGE Consortium, and Arianna Orsini, Luca Mastracci, Isotta Bozzarelli, Anna Ferrari, Federica Isidori, Roberto Fiocca, Marialuisa Lugaresi, Antonietta D’Errico, Deborah Malvi, Erica Cataldi-Stagetti, Paola Spaggiari, Anna Tomezzoli, Luca Albarello, Ari Ristimäki, Luca Bottiglieri, Kausilia K. Krishnadath, Riccardo Rosati, Uberto Fumagalli Romario, Giovanni De Manzoni, Jari Räsänen, Giovanni Martinelli, Sandro Mattioli, Elena Bonora, EACSGE Consortium

Subjects
Cancer Research, HNF1alpha, esophageal adenocarcinoma, Oncology, TP53, SMAD4, Human medicine
Abstract

Simple Summary The molecular heterogeneity of esophageal adenocarcinoma (EAC), a severe malignancy with increasing incidence and low survival rates, misperceives the underlying biology of tumor onset and development. However, advances in high-throughput next-generation sequencing (NGS) technologies have highlighted the potential role of somatic DNA sequence markers for new diagnostic techniques or constitute novel therapeutic targets. Thus, in order to identify a molecular and prognostic signature in EAC patients, we decided to integrate the sequencing of specimens from naive patients (not treated with chemo-radiotherapy) with histological classification, with the aim of identification of potential biomarkers, and patient stratification. Combining different approaches paves the way for early identification and the selection of better therapy. Esophageal adenocarcinoma (EAC) is a severe malignancy with increasing incidence, poorly understood pathogenesis, and low survival rates. We sequenced 164 EAC samples of naive patients (without chemo-radiotherapy) with high coverage using next-generation sequencing technologies. A total of 337 variants were identified across the whole cohort, with TP53 as the most frequently altered gene (67.27%). Missense mutations in TP53 correlated with worse cancer-specific survival (log-rank p = 0.001). In seven cases, we found disruptive mutations in HNF1alpha associated with other gene alterations. Moreover, we detected gene fusions through massive parallel sequencing of RNA, indicating that it is not a rare event in EAC. In conclusion, we report that a specific type of TP53 mutation (missense changes) negatively affected cancer-specific survival in EAC. HNF1alpha was identified as a new EAC-mutated gene.

Published
2023

11. Identification of Novel Molecular Subgroups in Esophageal Adenocarcinoma to Predict Response to Neo-Adjuvant Therapies

Author

Hoefnagel, Sanne J. M., primary, Koemans, Willem J., additional, Khan, Hina N., additional, Koster, Jan, additional, Meijer, Sybren L., additional, van Dieren, Jolanda M., additional, Kodach, Liudmila L., additional, van Sandick, Johanna W., additional, Calpe, Silvia, additional, del Sancho-Serra, Carmen M., additional, Correia, Ana C. P., additional, Van Berge Henegouwen, Mark I., additional, Gisbertz, Suzanne S., additional, Hulshof, Maarten C. C. M., additional, Mattioli, Sandro, additional, Spaander, Manon C. W., additional, and Krishnadath, Kausilia K., additional

Published
2022
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14. 490. CORRELATION BETWEEN HISTOLOGICAL AND MOLECULAR ALTERATIONS WITH POOR SURVIVAL IN ESOPHAGEAL ADENOCARCINOMA

Author

Bonora, Elena, primary, Mastracci, Luca, additional, Orsini, Arianna, additional, Bozzarelli, Isotta, additional, Isidori, Federica, additional, Tassi, Valentina, additional, Fiocca, Roberto, additional, Lugaresi, Marialuisa, additional, D'Errico, Antonietta, additional, Malvi, Deborah, additional, Spaggiari, Paola, additional, Tomezzoli, Anna, additional, Albarello, Luca, additional, Ristimäki, Ari, additional, Bottiglieri, Luca, additional, Krishnadath, Kausilia, additional, Rosati, Riccardo, additional, Romario, Uberto Fumagalli, additional, De Manzoni, Giovanni, additional, Räsänen, Jari, additional, and Mattioli, Sandro, additional

Published
2022
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18. 456. THE PROGNOSTIC IMPACT OF TUMOR BUDDING IN ESOPHAGEAL ADENOCARCINOMA

Author

Fiocca, Roberto, primary, Mastracci, Luca, additional, Lugaresi, Marialuisa, additional, Grillo, Federica, additional, D'Errico, Antonietta, additional, Malvi, Deborah, additional, Spaggiari, Paola, additional, Tomezzoli, Anna, additional, Albarello, Luca, additional, Ristimäki, Ari, additional, Bottiglieri, Luca, additional, Bonora, Elena, additional, Krishnadath, Kausilia K, additional, Rosati, Riccardo, additional, Romario, Uberto Fumagalli, additional, De Manzoni, Giovanni, additional, Räsänen, Jari, additional, and Mattioli, Sandro, additional

Published
2022
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22. Identification of Novel Molecular Subgroups in Esophageal Adenocarcinoma to Predict Response to Neo-Adjuvant Therapies

Author

Hoefnagel, Sanne J. M., Koemans, Willem J., Khan, Hina N., Koster, Jan, Meijer, Sybren L., van Dieren, Jolanda M., Kodach, Liudmila L., van Sandick, Johanna W., Calpe, Silvia, del Sancho-Serra, Carmen M., Correia, Ana C. P., Henegouwen, Mark I. Van Berge, Gisbertz, Suzanne S., Hulshof, Maarten C. C. M., Mattioli, Sandro, Spaander, Manon C. W., Krishnadath, Kausilia K., Hoefnagel, Sanne J. M., Koemans, Willem J., Khan, Hina N., Koster, Jan, Meijer, Sybren L., van Dieren, Jolanda M., Kodach, Liudmila L., van Sandick, Johanna W., Calpe, Silvia, del Sancho-Serra, Carmen M., Correia, Ana C. P., Henegouwen, Mark I. Van Berge, Gisbertz, Suzanne S., Hulshof, Maarten C. C. M., Mattioli, Sandro, Spaander, Manon C. W., and Krishnadath, Kausilia K.

Abstract

Esophageal adenocarcinoma (EAC) is a highly aggressive cancer and its response to chemo- and radiotherapy is unpredictable. EACs are highly heterogeneous at the molecular level. The aim of this study was to perform gene expression analysis of EACs to identify distinct molecular subgroups and to investigate expression signatures in relation to treatment response. In this prospective observational study, RNA sequencing was performed on pre-treatment endoscopic EAC biopsies from a discovery cohort included between 2012 and 2017 in one Dutch Academic Center. Four additional cohorts were analyzed for validation purposes. Unsupervised clustering was performed on 107 patients to identify biological EAC subgroups. Specific cell signaling profiles were identified and evaluated with respect to predicting response to neo-adjuvant chemo(radio)therapy. We identified and validated three distinct biological EAC subgroups, characterized by (1) p38 MAPK/Toll-like receptor signaling; (2) activated immune system; and (3) impaired cell adhesion. Subgroup 1 was associated with poor response to chemo-radiotherapy. Moreover, an immune signature with activated T-cell signaling, and increased number of activated CD4 T memory cells, neutrophils and dendritic cells, and decreased M1 and M2 macrophages and plasma cells, was associated with complete histopathological response. This study provides a novel molecular classification for EACs. EAC subgroup 1 proved to be more therapy-resistant, while immune signaling was increased in patients with complete response to chemo-radiotherapy. Our findings give insight into the biology of EACs and in cellular signaling mechanisms underlying response to neo-adjuvant treatment. Future implementation of this classification will improve patient stratification and enhance the development of targeted therapies.

Published
2022

26. Prognostic Significance of Pulmonary Multifocal Neuroendocrine Proliferation With Typical Carcinoid

Author

Tassi, Valentina, primary, Scarnecchia, Elisa, additional, Ferolla, Piero, additional, Mete, Ozgur, additional, Manjula, Maganti, additional, Allison, Frances, additional, Potenza, Rossella, additional, Vannucci, Jacopo, additional, Ceccarelli, Silvia, additional, Yasufuku, Kazuhiro, additional, De Perrot, Marc, additional, Pierre, Andrew, additional, Darling, Gail, additional, Colella, Renato, additional, Ascani, Stefano, additional, Mattioli, Sandro, additional, Keshavjee, Shaf, additional, Waddell, Thomas Kenneth, additional, Puma, Francesco, additional, and Daddi, Niccolò, additional

Published
2022
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33. Genomic profiles of primary and metastatic esophageal adenocarcinoma identified via digital sorting of pure cell populations: results from a case report

Author

Isidori, Federica, Malvi, Deborah, Fittipaldi, Silvia, Forcato, Claudio, Bozzarelli, Isotta, Sala, Claudia, Raulli, Giovanni, D'Errico, Antonia, Fiorentino, Michelangelo, Seri, Marco, Krishnadath, Kausilia K., Bonora, Elena, Mattioli, Sandro, Lugaresi, Maria Luisa, D'Errico, Antonietta, Castellani, Gastone, Fiocca, Roberto, Mastracci, Luca, Räsänen, Jari, Söderström, Henna, CCA - Imaging and biomarkers, Gastroenterology and Hepatology, AGEM - Re-generation and cancer of the digestive system, Isidori, Federica, Malvi, Deborah, Fittipaldi, Silvia, Forcato, Claudio, Bozzarelli, Isotta, Sala, Claudia, Raulli, Giovanni, D'Errico, Antonia, Fiorentino, Michelangelo, Seri, Marco, Krishnadath, Kausilia K., Bonora, Elena, Mattioli, Sandro, Lugaresi, Maria Luisa, Castellani, Gastone, Fiocca, Roberto, Mastracci, Luca, Räsänen, Jari, and Söderström, Henna

Subjects
0301 basic medicine, Cancer Research, Esophageal Neoplasms, Receptor, ErbB-2, Biopsy, medicine.medical_treatment, Case Report, Somatic evolution in cancer, Targeted therapy, ErbB-2, 0302 clinical medicine, Surgical oncology, Neoplasm Metastasis, Stage (cooking), Esophageal Neoplasm, Tumor, medicine.diagnostic_test, Single Nucleotide, Genomics, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Immunohistochemistry, Neoplasm Metastasi, Oncology, 030220 oncology & carcinogenesis, Adenocarcinoma, Female, Esophageal adenocarcinoma, Human, Receptor, Stromal cell, Polymorphism, Single Nucleotide, lcsh:RC254-282, Clonal Evolution, 03 medical and health sciences, Genetic, Next generation sequencing, Biomarkers, Tumor, Genetics, medicine, Humans, Polymorphism, Neoplasm Staging, Digital cell sorting, Esophageal adenocarcinoma, Next generation sequencing, Adenocarcinoma, Biomarkers, Tumor, Biopsy, Clonal Evolution, Esophageal Neoplasms, Female, Humans, Immunohistochemistry, Mutation, Neoplasm Metastasis, Neoplasm Staging, Polymorphism, Single Nucleotide, Receptor, ErbB-2, Genomics, Whole Genome Sequencing, Whole Genome Sequencing, business.industry, Cancer, medicine.disease, Digital cell sorting, 030104 developmental biology, Mutation, Genomic, Cancer research, business, Biomarkers
Abstract

Background We report on a female patient who underwent primary radical resection for a stage 2B Her-2-positive Barrett’s-type esophageal adenocarcinoma (EAC). Despite Her-2 targeted therapy, her disease recurred and required repeated metastectomies. Case presentation Digital cell sorting and targeted sequencing of cancer sub-clones from EAC and metastases revealed a completely mutated TP53, whereas the sorted stromal cells were wild-type. Her-2 amplification was significantly lower in the metastases when the patient became therapy-resistant. Conclusions The mechanism of therapy resistance illustrated by this case could only be detected through accurate analysis of tumor sub-populations. Investigating tumor sub-populations of recurrent disease is important for adjusting therapy in recurrent EAC. Electronic supplementary material The online version of this article (10.1186/s12885-018-4789-4) contains supplementary material, which is available to authorized users.

Published
2018

34. The Prognostic Impact of Histology in Esophageal and Esophago-Gastric Junction Adenocarcinoma

Author

Fiocca, Roberto, primary, Mastracci, Luca, additional, Lugaresi, Marialuisa, additional, Grillo, Federica, additional, D’Errico, Antonietta, additional, Malvi, Deborah, additional, Spaggiari, Paola, additional, Tomezzoli, Anna, additional, Albarello, Luca, additional, Ristimäki, Ari, additional, Bottiglieri, Luca, additional, Bonora, Elena, additional, Krishnadath, Kausilia K., additional, Raulli, Gian Domenico, additional, Rosati, Riccardo, additional, Fumagalli Romario, Uberto, additional, De Manzoni, Giovanni, additional, Räsänen, Jari, additional, and Mattioli, Sandro, additional

Published
2021
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35. Total gastrectomy versus upper pole gastrectomy for the surgical therapy of Siewert type II adenocarcinoma of the esophagus: pathology may drive the choice

Author

Lugaresi, Marialuisa, primary, Mattioli, Benedetta, additional, Daddi, Niccolò, additional, Pilotti, Vladimiro, additional, Ferruzzi, Luca, additional, Raulli, GianDomenico, additional, Malvi, Deborah, additional, D’Errico, Antonietta, additional, Fiocca, Roberto, additional, and Mattioli, Sandro, additional

Published
2021
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