Ontology type: schema:ScholarlyArticle Open Access: True
2015-12
AUTHORSIngrid Garajová, Niccola Funel, Michelangelo Fiorentino, Valentina Agostini, Manuela Ferracin, Massimo Negrini, Giovanni Luca Frassineti, Giampaolo Gavelli, Adam Enver Frampton, Guido Biasco, Elisa Giovannetti
ABSTRACTBACKGROUND: 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. FINDINGS: 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. More... »
PAGES129
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