title: CDX-2 Expression in Primary Lung Adenocarcinoma.
abstract: Adenocarcinoma with enteric differentiation is a rare subtype of lung adenocarcinoma that is recognized as a variant type of primary adenocarcinoma in the 2015 World Health Organization classification of lung tumors. Published immunohistochemistry studies show variable staining pattern for CDX-2 ranging from positivity in 71% of the cases to no staining. As little is known about CDX-2 expression in lung adenocarcinomas lacking histologic features of enteric differentiation, our aim was to determine the rate of CDX-2 positivity in non-enteric-type lung adenocarcinomas. We performed immunohistochemistry for CDX-2, CK7, CK20, TTF-1, napsin A, and p40 using 4-μm sections of a previously constructed tissue microarray containing 93 primary lung adenocarcinomas that lack morphologic evidence of enteric differentiation. The cohort included 22 well, 54 moderately, and 17 poorly differentiated tumors (55 female, 38 male; age range: 42 to 86, median: 64.5). All 93 tumors were strongly CK7 positive, whereas variable CK20 staining was seen in 4 tumors (1 strong, 1 moderate, and 2 focal). Both TTF-1 and napsin A were positive in 81 of 93 (87%) tumors with only 6 of 93 (6.5%) tumors negative for both the markers. Eleven tumors were CDX-2 positive (5 strong, 3 moderate, and 3 weak), all of which were also TTF-1 and napsin A positive and p40 negative. One CDX-2-positive tumor showed focal CK20 staining. Mutation studies for EGFR/K-ras/ALK were performed in four CDX-2-positive tumors and detected a K-ras mutation in one of them. CDX-2 positivity can be seen in a subset (12%) of lung adenocarcinoma. These tumors are CK7, TTF-1, and napsin A positive and p40 negative. Focal CK20 staining is only seen in rare cases. CDX-2 positivity should not be used as the only criteria to exclude lung origin.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD.
authors.forename: Morgan L
authors.initials: ML
authors.lastname: Cowan
authors.forename: Qing K
authors.initials: QK
authors.lastname: Li
authors.forename: Peter B
authors.initials: PB
authors.lastname: Illei
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D016282:Aspartic Acid Endopeptidases / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D000071616:CDX2 Transcription Factor; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D015870:Gene Expression; D014644:Genetic Variation; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D053554:Keratin-20 / Q000235:genetics; D053552:Keratin-7 / Q000235:genetics; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009687:Nuclear Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D012680:Sensitivity and Specificity; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics; D000095043:Cyclin-Dependent Kinase-Activating Kinase
chemical_list: D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; C117307:KRAS protein, human; D053554:Keratin-20; D053552:Keratin-7; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D018844:Cyclin-Dependent Kinases; D016282:Aspartic Acid Endopeptidases; C498549:NAPSA protein, human; D016283:Proto-Oncogene Proteins p21(ras); D000095043:Cyclin-Dependent Kinase-Activating Kinase