Introduction Pancreatic adenocarcinomas are resistant to medical therapies and associated with a poor prognosis. Sulfatase 2 (SULF2) is one of two extracellular heparan sulphate 6-O-endosulfatases that modulate ligand activated FGF and Wnt signalling. SULF2 expression is dramatically upregulated at mRNA levels in pancreatic cancers (NCBI GEO). We have investigated SULF2 protein expression in pancreatic adenocarcinomas, in association with clinicopathological parameters.
Methods Immunohistochemistry for SULF2 was performed on archived FFPE (Formalin-Fixed paraffin Embedded) blocks from 21 resected primary pancreatic adenocarcinomas, most of which were histologically defined as ductal (19/21, 90.5%). Membranous and cytoplasmic expression of SULF2 in tumour and stromal cells were separately assessed. Additionally, immunostaining for α-Smooth Muscle Actin (a-SMA) was performed for further cell characterisation.
Results SULF2 was expressed in tumour cells in the majority of the tumours (18/21, 86%). This expression was either cytoplasmic (13/21, 61.9%), membranous (12/21, 57.1%) or both (17/21, 80.9%). Membranous positivity was found almost exclusively in tumours with low differentiated areas (11/12, p=0.007). Membranous overexpression was also associated with shorter patient survival (p=0.011). Spindle-shaped cells of desmoplastic tumour stroma showed strong cytoplasmic positivity in all tumours studied (21/21, 100%). These cells were also positive for a-SMA, a marker of activated pancreatic stellate cells. Non-neoplastic pancreas showed only focal positivity for SULF2; this involved mainly endothelial, and scattered epithelial cells of exocrine pancreas.
Conclusion SULF2 over- expression is common in pancreatic adenocarcinomas, in both the ductal cancer cells as well as the desmoplastic tumour stroma. Tumour cell membranous localisation and over expression is associated with a more aggressive tumour behaviour and poorer patient survival. SULF2 is a novel candidate biomarker in patients for pancreatic cancer, identifying those with a poorer prognosis, as well as those who may benefit from therapies inhibiting SULF2.
Competing interests None declared.
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