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.

An accurate and rapid detection of lymph node metastasis in non-small cell lung cancer patients based on one-step nucleic acid amplification assay

“…Its expression is well recognized in breast, prostate, and colorectal epithelial cells. It has also been reported that AGR2 expression is predominant in adenocarcinoma as compared to squamous cell carcinoma in NSCLC [23]. Because not all primary lesions expressed AGR2, we excluded it from marker for OSNA assay.…”

Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression

“…Also of interest are AGR2, KRT8, and SFN. AGR2 is a known proto-oncogene recently confirmed to be overexpressed in lung adenocarcinoma (Pizzi et al 2012), and has been shown to promote cell proliferation and migration in several different cancers (Ramachandran et al 2008;Vanderlaag et al 2010;Park et al 2011). KRT8, encoding keratin 8, was previously reported to be up-regulated in lung adenocarcinoma (Wikman et al 2002); and SFN, encoding stratifin, has been reported to be overexpressed in early invasive lung adenocarcinoma (Shiba-Ishii et al 2011).…”

Immunohistochemical panel for distinguishing esophageal adenocarcinoma from squamous cell carcinoma: a combination of p63, cytokeratin 5/6, MUC5AC, and anterior gradient homolog 2 allows optimal subtyping

“…In a recent analysis, Long and Hornick [11] demonstrated that 80% of esophageal and 90% of anal squamous cell carcinomas express SOX2, with less than 20% of adenocarcinomas at these sites demonstrating expression. Anterior gradient homolog 2 (AGR2) encodes a 17-kd protein expression of which has been identified in adenocarcinomas of varying sites, including lung, breast, and prostate [12][13][14][15]. We recently identified increased levels of expression of AGR2 in esophageal adenocarcinoma [16].…”