Cancers (Feb 2023)
Correlations between Molecular Alterations, Histopathological Characteristics, and Poor Prognosis in Esophageal Adenocarcinoma
- 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,
- on behalf of the EACSGE Consortium
Affiliations
- Arianna Orsini
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy
- Luca Mastracci
- Unit of Anatomic Pathology, Ospedale Policlinico San Martino IRCCS, 16125 Genova, Italy
- Isotta Bozzarelli
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy
- Anna Ferrari
- IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
- Federica Isidori
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy
- Roberto Fiocca
- Unit of Anatomic Pathology, Ospedale Policlinico San Martino IRCCS, 16125 Genova, Italy
- Marialuisa Lugaresi
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy
- Antonietta D’Errico
- Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy
- Deborah Malvi
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy
- Erica Cataldi-Stagetti
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy
- Paola Spaggiari
- Unit of Anatomic Pathology, Humanitas University, 20089 Milan, Italy
- Anna Tomezzoli
- Unit of Anatomic Pathology, Azienda Ospedaliera di Verona, 37122 Verona, Italy
- Luca Albarello
- Pathology Unit, San Raffaele Scientific Institute, 20135 Milan, Italy
- Ari Ristimäki
- Department of Pathology, HUSLAB and HUS Diagnostic Center, University of Helsinki, 00170 Helsinki, Finland
- Luca Bottiglieri
- Unit of Anatomic Pathology, Istituto Europeo di Oncologia, 20122 Milan, Italy
- Kausilia K. Krishnadath
- Laboratory of Experimental Medicine and Pediatrics (LEMP), Department of Gastroenterology and Hepatology, University Hospital Antwerp, 2650 Antwerp, Belgium
- Riccardo Rosati
- Department of Gastrointestinal Surgery, San Raffaele Hospital, Vita-Salute San Raffaele University, 20135 Milan, Italy
- Uberto Fumagalli Romario
- Digestive Surgery, European Institute of Oncology, IRCCS, 20122 Milan, Italy
- Giovanni De Manzoni
- Department of Surgery, General and Upper G.I. Surgery Division, University of Verona, 37126 Verona, Italy
- Jari Räsänen
- Department of General Thoracic and Esophageal Surgery, Helsinki University Hospital, 00170 Helsinki, Finland
- Giovanni Martinelli
- IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
- Sandro Mattioli
- Division of Thoracic Surgery, Maria Cecilia Hospital, GVM Care & Research Group, Cotignola, 48022 Ravenna, Italy
- Elena Bonora
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy
- on behalf of the EACSGE Consortium
- DOI
- https://doi.org/10.3390/cancers15051408
- Journal volume & issue
-
Vol. 15,
no. 5
p. 1408
Abstract
Esophageal adenocarcinoma (EAC) is a severe malignancy with increasing incidence, poorly understood pathogenesis, and low survival rates. We sequenced 164 EAC samples of naïve 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.
Keywords
