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Appl Immunohistochem Mol Morphol. 2012 Jan;20(1):31-6. doi: 10.1097/PAI.0b013e3182233f9f.

Anterior gradient 2 overexpression in lung adenocarcinoma.

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  • 1Department of Medical Diagnostic Sciences & Special Therapies, University of Padova, Padova, Italy.


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.

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