Colorectal cancers are believed to arise predominantly from adenomas. Although these precancerous lesions have been subjected to extensive clinical, pathologic, and molecular analyses, little is currently known about the global gene expression changes accompanying their formation. To characterize the molecular processes underlying the transformation of normal colonic epithelium, we compared the transcriptomes of 32 prospectively collected adenomas with those of normal mucosa from the same individuals. Important differences emerged not only between the expression profiles of normal and adenomatous tissues but also between those of small and large adenomas. A key feature of the transformation process was the remodeling of the Wnt pathway reflected in patent overexpression and underexpression of 78 known components of this signaling cascade. The expression of 19 Wnt targets was closely correlated with clear up-regulation of KIAA1199, whose function is currently unknown. In normal mucosa, KIAA1199 expression was confined to cells in the lower portion of intestinal crypts, where Wnt signaling is physiologically active, but it was markedly increased in all adenomas, where it was expressed in most of the epithelial cells, and in colon cancer cell lines, it was markedly reduced by inactivation of the B-catenin/T-cell factor(s) transcription complex, the pivotal mediator of Wnt signaling. Our transcriptomic profiles of normal colonic mucosa and colorectal adenomas shed new light on the early stages of colorectal tumorigenesis and identified KIAA1199 as a novel target of the Wnt signaling pathway and a putative marker of colorectal adenomatous transformation.

Nodular regenerative hyperplasia (NRH) is an uncommon liver disease characterised histologically by numerous small hyperplastic nodules that are not separated by fibrotic tissue. It is thought to be the result of obliterative vasculopathy, and it has been associated with chronic use of medications, toxic substances and a wide variety of systemic diseases. Imaging diagnosis of early-stage NRH remains problematic. The nodules are rarely discerned and their appearance and behaviour before and after contrast medium administration are heterogeneous and not specific. A review of the literature shows that ultrasound has succeeded on occasion in revealing small focal liver lesions in patients with NRH. To our knowledge, there has been no published data on the performance in this setting of last-generation ultrasound scanners and techniques such as contrast-enhanced ultrasound (CEUS). The question is an important one because abdominal ultrasound is widely used as a first-line imaging technique for the evaluation of liver disease, and this makes it particularly suitable as a potential tool for the early diagnosis of NRH. Owing to the prolonged subclinical period and the limited help provided by imaging, the diagnosis in vivo of NRH is currently frequently missed, and it is still made exclusively on the basis of liver biopsy. In conclusion, this report describes 4 cases of biopsy-proven NRH that have been diagnosed over the past 2 years by our group. All were characterised by known comorbidities that confer a predisposition to NRH and by a peculiar parenchymal ultrasound pattern that we refer to as the "atoll sign".

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