title: Anterior gradient 2 overexpression in lung adenocarcinoma.
abstract: The histologic subtyping of the 2 major histotypes of nonsmall-cell lung cancer, that is, adenocarcinoma (AdC) and squamous cell carcinoma (SCC), is crucial to therapeutic decision making, but making this distinction can be a challenge. Querying the Oncomine database pinpointed anterior gradient 2 (AGR2) as being upregulated in lung AdC. On applying both quantitative real-time polymerase chain reaction and immunohistochemistry, this study tested the reliability of AGR2 status as a histotype-specific marker of lung AdC. AGR2 immunohistochemistry expression was semiquantitatively assessed in 120 cases of lung cancer (60 AdCs, 60 SCCs); 35 additional tissue samples from non-neoplastic lungs were considered as normal controls. To further support our findings, the expression of AGR2 mRNA was tested by quantitative real-time polymerase chain reaction in 30 of the considered cases (10 AdCs, 10 SCCs, and 10 normal lungs). AGR2 was consistently expressed in normal bronchial/bronchiolar columnar cells. Cases of AdC always expressed the protein (staining moderately in 30% and strongly in 70%), whereas none of the SCC cases strongly expressed AGR2 (staining was negative in 55%, weak in 33%, and moderate in 12%). AGR2 mRNA was significantly overexpressed in AdCs by comparison with SCCs (P=0.003) or normal lung tissue (P=0.002). AGR2 is upregulated in lung AdC (by comparison with either SCC or normal bronchial/bronchiolar columnar cells). AGR2 protein expression may support the histologic subtyping of nonsmall-cell lung cancer and be of clinical value in differentiating lung AdC from SCC.
authors.affiliation: Department of Medical Diagnostic Sciences & Special Therapies, University of Padova, Padova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Pizzi
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.forename: Mariangela
authors.initials: M
authors.lastname: Balistreri
authors.forename: Alessandra
authors.initials: A
authors.lastname: Galligioni
authors.forename: Federico
authors.initials: F
authors.lastname: Rea
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012189:Retrospective Studies
chemical_list: C502296:AGR2 protein, human; D014408:Biomarkers, Tumor; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm