While there is evidence that specific T cell populations can promote the growth of established tumors, instances where T cell activity causes neoplasms to arise de novo are infrequent. Here, we employed two conditional mutagenesis systems to delete the TGF-β signaling pathway component Smad4 in T cells and observed the spontaneous development of massive polyps within the gastroduodenal regions of mice. The epithelial lesions contained increased levels of transcripts encoding IL-11, IL-6, TGF-β, IL-1β, and TNF-α, and lamina propria cells isolated from lesions contained abundant IL-17A + CD4 + T cells. Furthermore, we found that Smad4 deficiency attenuated TGF-β-mediated in vitro polarization of FoxP3 + CD4 + T cells, but not IL-17A + CD4 + T cells, suggesting that the epithelial lesions may have arisen as a consequence of unchecked Th17 cell activity. Proinflammatory cytokine production likely accounted for the raised levels of IL-11, a cytokine known to promote gastric epithelial cell survival and hyperplasia. Consistent with IL-11 having a pathogenic role in this model, we found evidence of Stat3 activation in the gastric polyps. Thus, our data indicate that a chronic increase in gut Th17 cell activity can be associated with the development of premalignant lesions of the gastroduodenal region.

A 56-year-old woman was noted to have a 5 cm to 6 cm long, irregular narrowing of the distal esophagus on an upper gastrointestinal series. Initial endoscopy revealed a polypoid mass in the distal esophagus and concurrent endoscopic ultrasound revealed changes typical of inflammation but no evidence of an obvious neoplastic process. Repeated biopsies revealed only inflammation with no evidence of malignancy. Only after prolonged acid suppression did biopsies reveal verrucous carcinoma of the esophagus. The patient underwent a trans-hiatal esophagectomy and has remained well with no evidence of progression since. Verrucous carcinoma is a rare variant of squamous cell carcinoma, taking on a papillary or warty appearance grossly. Histological diagnosis may be difficult because this tumour typically shows no high-grade dysplasia. Therefore, diagnosis can be challenging, often requiring multiple sets of endoscopic biopsies due to the overlying hyperkeratotic layer. Of the 20 cases that have been reported, this is the second to provide an endosonographic description and the first to describe a change in endoscopic appearance with acid suppression.

The c-erbB-2 oncogene has been shown to be amplified in a variety of human adenocarcinomas. Antibodies to the protein product, p185, have been used for immunostaining of paraffin-embedded material, and have demonstrated that high levels of c-erbB-2 protein expression correlate with gene amplification under certain conditions. In studies by others, amplification has been demonstrated in 40 per cent of tubular type adenocarcinomas of the stomach, and an immunohistochemical study on frozen tissue has demonstrated staining in 3 out of 10 cases. Our study, using paraffin-embedded material, demonstrates staining in 19 per cent of 126 cases using a polyclonal antibody. Of the positive cases, 75 per cent were tubular or papillary type (P less than 0.025), and prominent staining was restricted to this group. Three cases showed well-defined positive areas in keeping with clonal expression of p185. No specific staining of normal or dysplastic epithelium adjacent to the carcinomas was found.