Role and new perspectives of transforming growth factor-alpha (TGF-alpha) in adenocarcinoma of the gastro-oesophageal junction

The incidence of gastro-oesophageal junction (GEJ) adenocarcinoma is increa sing in Western countries and prognosis is poor since metastasis is most of ten present at diagnosis. We examined samples from 87 resected type II GEJ adenocarcinomas, 30 of these with endoscopic diagnostic biopsy material, to evaluate transforming growth factor alpha (TGF-alpha) expression and p53 o verexpression by immunohistochemistry and in situ hybridization (for TGF-al pha), in relation to biological and clinical behaviour. TGF-alpha messenger RNA (mRNA) and protein were detectable in neoplastic cells in 56% and 64% cases respectively. TGF-alpha mRNA was detected in intra- and peritumoral l ymphocytes and those of metastatic lymph nodes, TGF-alpha protein expressio n was significantly associated with tumour progression (P = 0.025) and lymp h node metastasis (P < 0.05). The strong TGF-alpha expression found in neop lastic cells inside blood and lymphatic vessels and in metastatic localizat ions suggests that TGF-alpha-positive GEJ adenocarcinomas could have a more aggressive biological phenotype. The expression of TGF-alpha mRNA and prot ein in both inflammatory and neoplastic cells indicates that TGF-alpha is d irectly synthesized by both cell compartments. Finally, since TGF-alpha exp ression was associated with lymph node metastasis, its detection in preoper ative perendoscopic biopsies might identify patients with more aggressive t umours who may need additional therapy, including neo-adjuvant treatment. ( C) 2000 Cancer Research Campaign.