Nuclear Symmetric Dimethylarginine Staining is Indicative of Pancreatic Ductal Adenocarcinoma.

Objective: The protein arginine methyltransferase 5 (PRMT5) is a type II PRMT that is responsible for the majority of symmetric dimethylarginine (SDMA) in eukaryotic cells. While PRMT5 is overexpressed in pancreatic ductal adenocarcinoma (PDAC), the SDMA expression patterns in PDAC tissues have not been examined. This study is aimed to characterize the SDMA expression patterns in PDAC cells and patient tissues.

Methods: Tissue microarray (TMA), immunohistochemistry (IHC) of PDAC cell lines and archival PDAC tissue blocks, and western blotting were applied to this study.

Results: Expression of PRMT5 and SDMA is elevated in PANC-1 and MIA PaCa-2 cells compared with that in the pancreatic ductal HPNE cell line. Pharmacological inhibition of PRMT5 reduces the SDMA level, indicating that PRMT5 is primarily responsible for SDMA in PDAC cells. IHC staining of the TMA containing 158 patient samples demonstrates that nuclear SDMA staining is significantly enhanced in PDAC tissues compared to normal and tumor adjacent tissues. The elevated SDMA level is evident in tissues from patients with early-stage PDAC, which is further verified using the archival PDAC tissue blocks. In addition, the SDMA staining is highly clustered in the Islets of Langerhans of the pancreas, irrespective of the disease states.

Conclusions: We demonstrate for the first time that nuclear SDMA staining is significantly enhanced in PDAC tissues and in the Islets of Langerhans of the pancreas, indicating novel tissue IHC markers for PDAC and the endocrine units of the pancreas.