For the p53 Special IssueIn this article, we survey the major p53 (TP53) alterations identified in gastric carcinomas and their precursors. These include p53 expression, mutations, and loss of heterozygosity (LOH). Not only are the various abnormalities summarized, but in addition there is a survey of the literature with respect to the impact of these changes on patient prognosis and treatment response. The majority of published studies involve the immunohistochemical detection of the protein. These use different antibodies, different detection techniques, and different methods of interpretation. Therefore not surprisingly, the results of many of the studies are contradictory with one another. Overall, however, it appears that p53 alterations occur early in the development of gastric carcinoma, being present even in the nonneoplastic mucosa and they increase in frequency as one progresses along the pathway of gastric carcinoma development. p53 immunoreactivity is seen in 17%-90.7% of invasive gastric carcinomas. p53 alterations occur much more commonly in proximal lesions than in distal ones, suggesting that the molecular events leading to the development of gastric carcinoma may be very different in proximal vs. distal tumors. p53 mutations occur in 0%-77% of gastric carcinomas. The mutations are distributed widely across the gene from exons 4-11 with hot spots of mutation at codons 175, 248, 273, 282, 245, and 213. G:C>A:T transitions at CpG sites are the commonest type of mutation. At least 60% of carcinomas with mutations also exhibit p53 LOH. Hum Mutat 21:258-270,

Until recently, two major forms of colorectal epithelial polyp were recognized: the adenoma and the hyperplastic polyp. Adenomas were perceived to represent the precursor to colorectal cancer, whereas hyperplastic polyps were viewed as innocuous lesions with no potential for progression to malignancy. We now recognize, however, that the lesions formerly classified as hyperplastic actually represent a heterogeneous group of polyps, some of which have a significant risk for neoplastic transformation. These serrated polyps include not only hyperplastic polyps but also traditional serrated adenomas and sessile serrated adenomas. These polyps demonstrate characteristic molecular alterations not commonly seen in colorectal adenomas, and they probably progress to colorectal cancer by means of a new pathway: the serrated neoplasia pathway. The morphologic features of serrated colorectal lesions, the molecular alterations that characterize them, and their role in colorectal cancer development are discussed herein.

To our knowledge, this is the largest American single-center experience demonstrating that CBE-EMR with close endoscopic surveillance is an effective treatment modality for BE with HGD/IMC. Although the rate of stenosis development is significant, it is easily treated by endoscopic dilation. Patients considering endoscopic ablation should be counseled appropriately. The role of CBE-EMR in patients with lymphatic invasion or superficial submucosal invasion remains to be defined.

In genomic analyses of BE tissues from patients with or without later progression to HGD or EAC, we found significantly higher numbers of TP53 mutations in BE from patients with subsequent progression. These mutations were frequently detected before the onset of dysplasia or substantial changes in copy number.

CBE-EMR is a safe and highly effective long-term treatment that should be offered to all patients with Barrett's esophagus with HGD and IMC.