Up-regulated cytoplasmic expression, with reduced membranous distribution, of the src substrate p120(ctn) in gastric...

p120(ctn) is a substrate of the tyrosine kinase pp60 src. Tyrosine kinases such as src localize to the adherens junctions and phosphorylate junctional proteins in both normal and transformed cells.(1) p120(ctn) forms a complex with E-cadherin at the adherens junction and is phosphorylated by ligands such as epidermal growth factor receptor as well as pp60 src. Phosphorylation of p120(ctn) has been shown to correlate with cell transformation. The aim of this study was to investigate in vivo expression of p120(ctn) in gastric carcinoma and to examine any relationship to pathological characteristics and patient survival. Immunohistochemical staining for p120(ctn) was performed in 68 gastric carcinoma specimens (19 diffuse, 49 intestinal type), in 22 lymph node metastases, and in gastric mucosal biopsies from 16 patients with gastric dysplasia and ten healthy controls. Up-regulation of p120(ctn) cytoplasmic staining was seen in six (37 per cent) of the gastric dysplasia cases and in 45 (66 per cent) tumours (89 per cent of diffuse and 57 per cent of intestinal tumours). Loss of membranous distribution of staining for p120(ctn) was seen in 22 (32 per cent) tumours (52 per cent of diffuse and 24 per cent of intestinal tumours). The staining pattern in the primary tumour showed no correlation with tumour type, grade, or stage, or patient survival. Of 22 lymph node metastases examined, 13 (60 per cent) showed loss of membranous staining. In conclusion, staining for p120(ctn) in gastric carcinoma and dysplasia revealed marked up-regulation of cytoplasmic staining, sometimes associated with reduced membranous expression. Up-regulation of expression of p120(ctn) has not previously been described in human epithelial malignancy. The significance of these findings is uncertain, but they may reflect a change in tyrosine kinase signal transduction pathways, and a role for p120(ctn) in ligand-induced mitogenic signalling and cell transformation.