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