MicroRNA profiling of primary pulmonary enteric adenocarcinoma in members from the same family reveals some similarities to pancreatic adenocarcinoma-A step towards personalized therapy

  • I. G
  • N. F
  • M. F
  • et al.
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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. 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 formalinfixed, 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.Copyright © 2015 Garajova et al.

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I., G., N., F., M., F., V., A., M., F., M., N., … G., B. (2015). MicroRNA profiling of primary pulmonary enteric adenocarcinoma in members from the same family reveals some similarities to pancreatic adenocarcinoma-A step towards personalized therapy. Clinical Epigenetics, 7(1), 129. https://doi.org/http://dx.doi.org/10.1186/s13148-015-0162-5

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