title: MicroRNA profiling of primary pulmonary enteric adenocarcinoma in members from the same family reveals some similarities to pancreatic adenocarcinoma-a step towards personalized therapy.
abstract: BACKGROUND
  Primary pulmonary enteric adenocarcinoma (PEAC) is defined as a pulmonary adenocarcinoma with a predominant component of intestinal differentiation and tumor cells positive for at least one intestinal marker. The aim of the present study was the molecular and histological characterization of a PEAC from a patient with two other family members affected by similar lung tumors, which has never been reported before.
  
  
  RESULTS
  We evaluated the molecular characteristics of the proband's PEAC by using a previously validated 47-microRNA (miRNA) cancer-specific array and a predictive method to estimate tissue-of-origin probabilities. Immunohistochemical (IHC) staining for thyroid transcription factor (TTF-1), napsin A, caudal-related homeobox 2 (CDX2), cytokeratins, and mucins, as well as mutational analyses for epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), and anaplastic lymphoma kinase (ALK) were performed on formalin-fixed, paraffin-embedded (FFPE) tissues. The occurrence of PEAC in two family members was associated with similar clinicopathological features (age at diagnosis, smoking habit, tumor localization, multiple colonic polyps), histologic findings (TTF-1 negativity and CDX2 positivity), and genetic findings (KRAS (Gly12Asp) mutation, but no EGFR/ALK aberrations). miRNA profiling revealed similarities with non-small cell lung cancer (NSCLC; 75.98 %) and some overlap with pancreatic ductal adenocarcinoma (PDAC; 23.34 %), but not with colorectal cancer (CRC; less than 0.5 %). Notably, these PEACs share key PDAC-associated miRNAs associated with tumor aggressiveness (miR-31*/-126*/-506/-508-3p/-514).
  
  
  CONCLUSIONS
  We describe for the first time PEAC in members from the same family, associated with similar clinical and genetic features. miRNA profiling of the PEAC resembled a NSCLC signature, with partial overlap to a PDAC pattern. This could explain its aggressive behavior and therefore help to guide future tailored-therapeutic approaches.
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, CCA room 1.52, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.|Department of Experimental, Diagnostic and Speciality Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Garajová
authors.affiliation: Division of General and Transplant Surgery, Pisa University Hospital, Via Paradisa 2, 56124 Pisa, Italy.|Cancer Pharmacology Lab, AIRC Start-Up Unit, University of Pisa, Lungarno Pacinotti 43, 56126 Pisa, Italy.
authors.forename: Niccola
authors.initials: N
authors.lastname: Funel
authors.affiliation: Department of Pathology, F. Addari Institute, S.Orsola Malpighi Hospital, University of Bologna, Viale Ercolani 4/2, 40138 Bologna, Italy.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Fiorentino
authors.affiliation: Department of Pathology, F. Addari Institute, S.Orsola Malpighi Hospital, University of Bologna, Viale Ercolani 4/2, 40138 Bologna, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Agostini
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Via Borsari 46, 44121 Ferrara, Italy.|Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Via Fossato di Mortara 70, 44121 Ferrara, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Ferracin
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Via Borsari 46, 44121 Ferrara, Italy.|Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Via Fossato di Mortara 70, 44121 Ferrara, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Negrini
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via Piero Maroncelli 40, 47014 Meldola, Italy.
authors.forename: Giovanni Luca
authors.initials: GL
authors.lastname: Frassineti
authors.affiliation: Department of Radiology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via Piero Maroncelli 40, 47014 Meldola, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Gavelli
authors.affiliation: HPB Surgical Unit, Department of Surgery & Cancer, Hammersmith Hospital Campus, Imperial College, Du Cane Road, London, W12 0HS UK.
authors.forename: Adam Enver
authors.initials: AE
authors.lastname: Frampton
authors.affiliation: Department of Experimental, Diagnostic and Speciality Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Biasco
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, CCA room 1.52, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.|Cancer Pharmacology Lab, AIRC Start-Up Unit, University of Pisa, Lungarno Pacinotti 43, 56126 Pisa, Italy.|Cancer Pharmacology Lab, Start-Up Unit, University of Pisa, via Paradisa 2, 56124 Pisa, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Giovannetti
keywords: Enteric; Immunohistochemistry; Intestinal; PEAC; Pulmonary adenocarcinoma