It is widely accepted that most colorectal cancers (CRCs) arise from colorectal adenomas (CRAs), but transcriptomic data characterizing the progression from colorectal normal mucosa to adenoma, and then to adenocarcinoma are scarce. These transition steps were investigated using microarrays, both at the level of gene expression and alternative pre-mRNA splicing. Many genes and exons were abnormally expressed in CRAs, even more than in CRCs, as compared to normal mucosae. Known biological pathways involved in CRC were altered in CRA, but several new enriched pathways were also recognized, such as the complement and coagulation cascades. We also identified four intersectional transcriptional signatures that could distinguish CRAs from normal mucosae or CRCs, including a signature of 40 genes differentially deregulated in both CRA and CRC samples. A majority of these genes had been described in different cancers, including FBLN1 or INHBA, but only a few in CRC. Several of these changes were also observed at the protein level. In addition, 20% of these genes (i.e. CFH, CRYAB, DPT, FBLN1, ITIH5, NR3C2, SLIT3 and TIMP1) showed altered pre-mRNA splicing in CRAs. As a global variation occurring since the CRA stage, and maintained in CRC, the expression and splicing changes of this 40-gene set may mark the risk of cancer occurrence from analysis of CRA biopsies.

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Aims-To investigate the immunohistochemical expression ofp53 protein in oesophageal squamous cell carcinomas and in dysplastic areas of the oesophageal mucosa surrounding the tumours.Methods-Biopsy samples were obtained from 20 patients with an oesophageal squamous cell carcinoma. Blocks of the tumours and of the surrounding mucosa were immunostained with the monoclonal antibody DO-7. Results-Fourteen of the 20 carcinomas were positive for p53 (70%). The frequency of p53 overexpression increased with the differentiation of the tumour. Nine out of 13 dysplastic specimens were positive for p53 (69%): eight cases with severe dysplasia and one case with moderate dysplasia. No p53 immunostaining was detected in normal oesophageal epithelium. All p53 positive dysplastic specimens were taken from the mucosa adjacent to tumours that were also immunostained. In moderate dysplastic mucosa the p53 positive cells were located in the proliferative basal zone, whereas in severe dysplasia the immunostained cells increased in number and spread to upper cell layers of the epithelium.Conclusion-This study supports the hypothesis that TP53 gene is frequently involved in the development of oesophageal squamous cell carcinoma and that p53 protein accumulation is an early event in human oesophageal carcinogenesis. (J7 Clin Pathol 1995;48:531-534)

Endoscopic ultrasound (endosonography) is useful in the preoperative staging of oesophageal tumours. It may also have a role in evaluation and surveillance of patients with inoperable carcinomas. Thirty four patients with inoperable oesophageal cancer were investigated by endosonography and computed tomography before medical treatment. In 10 patients receiving combined chemotherapy and radiotherapy, the endoscopic lesions resolved and biopsy specimens were negative. When endosonography suggested the persistence of tumour infiltration in these patients, a local recurrence or distant metastases appeared within a few months. In contrast, when no infiltration was detected, no tumoral recurrence or progression was observed within eight months. These results suggest that endosonography is better than endoscopic biopsy specimens and computed tomography in assessing the response of oesophageal carcinoma to non-surgical treatment. (Gut 1992; 33: 1459-1461 Assessing the response to chemotherapy in oesophageal carcinoma is not easy and is based on data provided by endoscopy, histopathology, and computed tomography. This study aimed to assess the usefulness of endosonography in the surveillance of these patients.