title: Pulmonary Adenocarcinoma With Enteric Differentiation: Immunohistochemistry and Molecular Morphology.
abstract: Pulmonary adenocarcinoma with enteric differentiation (PAED) is a rare subtype of lung adenocarcinoma recently recognized in the WHO classification. It is defined as an adenocarcinoma in which the enteric component exceeds 50% and have to show the expression of at least 1 immunohistochemical marker of enteric differentiation. Although the definition of this tumor type is very important, above all in the differential diagnosis between a primary lung tumor and a metastasis of colorectal adenocarcinoma, this cancer still lacks a distinctive immunohistochemical and molecular signature. We recruited the largest series in the literature of PAEDs according to the morphology and the positivity for intestinal markers. Then, we evaluated the immunohistochemical and molecular profile of these adenocarcinomas. In our series, CDX-2 and CK7 were the immunohistochemical markers mostly expressed by PAEDs. There was an inverse relationship between the expression of pnuemocytes markers, such as TTF-1, and intestinal markers. Molecular analysis revealed KRAS as the most frequently mutated gene (>60% of cases), with very few cases harboring abnormalities affecting EGFR, BRAF, and ALK genes. PAEDs are morphologically very heterogenous. The immunohistochemical profile based on CDX-2 and CK7 positivity of PAEDs appears very robust to support this diagnosis, and it is applicable also on small biopsies. KRAS appears as the most important mutated gene in such tumors.
authors.affiliation: Department of Diagnostics and Public Health.
authors.forename: Alessia
authors.initials: A
authors.lastname: Nottegar
authors.affiliation: Department of Molecular Biotechnology and Health Science, Center for Experimental Research and Medical Studies (CeRMS), University of Turin, Turin.|Departments of Pathology and Pharmacology, Weill Cornell Cancer Center, Weill Cornell Medical College, Cornell University, New York, NY.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Tabbò
authors.affiliation: Department of Diagnostics and Public Health.|Department of Pathology, Santa Chiara Hospital, Trento.
authors.forename: Claudio
authors.initials: C
authors.lastname: Luchini
authors.affiliation: Department of Diagnostics and Public Health.
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
authors.affiliation: Medical Oncology, University and Hospital Trust of Verona, Verona.
authors.forename: Emilio
authors.initials: E
authors.lastname: Bria
authors.affiliation: Department of Medicine (DIMED), University of Padua, Padua.
authors.forename: Nicola
authors.initials: N
authors.lastname: Veronese
authors.affiliation: Medical Oncology, University and Hospital Trust of Verona, Verona.
authors.forename: Antonio
authors.initials: A
authors.lastname: Santo
authors.affiliation: Medical Oncology, University and Hospital Trust of Verona, Verona.
authors.forename: Sara
authors.initials: S
authors.lastname: Cingarlini
authors.affiliation: Department of Diagnostics and Public Health.
authors.forename: Eliana
authors.initials: E
authors.lastname: Gilioli
authors.affiliation: Oncology Department, Fondazione Poliambulanza, Brescia.
authors.forename: Chiara
authors.initials: C
authors.lastname: Ogliosi
authors.affiliation: Department of Diagnostics and Public Health.
authors.forename: Albino
authors.initials: A
authors.lastname: Eccher
authors.affiliation: Department of Diagnostics and Public Health.
authors.forename: Licia
authors.initials: L
authors.lastname: Montagna
authors.affiliation: Department of Diagnostics and Public Health.
authors.forename: Serena
authors.initials: S
authors.lastname: Pedron
authors.affiliation: Department of Pathology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Doglioni
authors.affiliation: Department of Pathology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Cangi
authors.affiliation: Departments of Pathology and Pharmacology, Weill Cornell Cancer Center, Weill Cornell Medical College, Cornell University, New York, NY.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Inghirami
authors.affiliation: Department of Diagnostics and Public Health.
authors.forename: Marco
authors.initials: M
authors.lastname: Chilosi
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000473:pathology; D056809:Alveolar Epithelial Cells / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D000071616:CDX2 Transcription Factor / Q000378:metabolism; D002454:Cell Differentiation; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000473:pathology; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D006801:Humans; D007150:Immunohistochemistry; D053552:Keratin-7 / Q000378:metabolism; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000473:pathology; D009154:Mutation / Q000235:genetics; D057089:Pathology, Molecular; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D000074482:Thyroid Nuclear Factor 1 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C117307:KRAS protein, human; D053552:Keratin-7; D000074482:Thyroid Nuclear Factor 1; D016283:Proto-Oncogene Proteins p21(ras)