Anterior gradient 2 and mucin 4 expression mirrors tumor cell differentiation in pancreatic adenocarcinomas, but aberrant anterior gradient 2 expression predicts worse patient outcome in poorly differentiated tumors

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Authors

BRYCHTOVA Veronika HERMANOVÁ Markéta KARASEK Petr LENZ Jiří SELINGEROVÁ Iveta VOJTESEK Borivoj KALA Zdeněk HRSTKA Roman

Year of publication 2014
Type Article in Periodical
Magazine / Source Pancreas
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.1097/MPA.0b013e3182a63bc3
Field Oncology and hematology
Keywords AGR2; immunohistochemistry; MUC4; pancreatic ductal adenocarcinoma
Description OBJECTIVES: This study aimed to determine anterior gradient 2 (AGR2) expression in biopsies from pancreatic ductal adenocarcinomas (PDACs) and to evaluate AGR2 as a potential independent prognostic factor. METHODS: Tissue sample sections from a cohort of 135 consecutive surgically resectable PDACs were subjected to semiquantitative immunohistochemical analysis of AGR2 and mucin 4 (MUC4) expression. RESULTS: Anterior gradient 2 was over-expressed in PDAC compared with normal ductal cells. Since tumor lesions of PDAC are heterogeneous and constitute structures with various differentiation states, expression of both AGR2 and MUC4 was evaluated in each separate component. Expression levels of both proteins reflected the degree of tumor differentiation. Generally, well differentiated regions of tumor lesions expressed high levels of both proteins, moderately differentiated regions showed less AGR2 and MUC4, and poorly differentiated structures showed only weak positivity or were entirely negative. Of particular interest were occasional cases of strong AGR2 expression in high-grade tumors, where elevated protein levels were associated with shorter patient survival. CONCLUSIONS: Anterior gradient 2 and MUC4 reflect the level of differentiation of PDACs. However, in less differentiated tumors, aberrantly elevated AGR2 expression predicts poor patient outcome.
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