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Adenoma serrato e polipi intestinali: nuovi aspetti e implicazioni cliniche Stefano Crippa Istituto Cantonale di Patologia Lugano, 7 marzo 2007 Serrated Polyp • Cooper et al. (1979) Adenomatous and carcinomatous changes within hyperplastic colonic epithelium • Urbanski et al. (1984) Mixed hyperplastic adenomatous polyps: an underdiagnosed entity. • Longacre, Fenoglio-Preiser (1990) Mixed hyperplastic adenomatous polyps/serrated adenomas: a distinct form of colorectal neoplasia • Torlakovic et al. (1996) Serrated adenomatous polyposis in humans « The hyperplastic polip can be defined as a lesion caused by the inibition of programmed cell death or apoptosis » J. R. Jass (2004) Response to tissue injury Genetic mechanism (Kras, BRAF, MLH1…) Serrated lesions pathway « Despite decades of research into the behaviour of adenoma, we still do not know which adenomas are aggressive » J. R. Jass (2004) « Inhibition of apoptosis characterises serrated polips, whereas loss of inhibition of proliferation is the mechanism underlying tubular adenomas » J. R. Jass (2004) serrated neoplasia pathway vs APC pathway (Vogelstein) Colon cancer stratification tubular normal mucosa tubulovillous adenocarcinoma MSS (Mucinouspoorly differentiated) metastasis (~85% of CRCs aneuploidy) villous serrated adenocarcinoma MSI-H (Mucinouspoorly differentiated) metastasis (~15% of CRCs aneuploidy) Diagrammatic Representation of the Serrated Neoplasia Pathway Proximal Colon Normal K-ras Mutation Hyperplastic Polyp BRAF Mutation Hyperplastic Polyp MLH1 methylation Proliferation Serrated Adenoma Mutation of TGF-B, IGF and BAX genes MSI-H carcinoma The RAS-RAF-MAPK signalling pathway Growth factor OUT P B GR Cyclic AMP RAS SOS Growth factor Adenylate cyclase G-protein P Tyrosine Kinase receptor P P BRAF P G-proteincoupled receptor P MEK ERK1 ERK2 P P P P Cytoplasm Changes in gene expression Nucleus Clinical relevance • Separate traditional hyperplastic polyp from sessile serrated adenoma which is truly a neoplastic lesion that can progress to carcinoma • Nomenclature • Follow-up guidelines Nomenclature • Polipo iperplastico • Adenoma dentellato sessile (usualmente displasia di basso grado) • Adenoma dentellato (displasia di basso o alto grado) • Polipo misto iperplastico/adenomatoso Summary • Sessile serrated adenoma, used to be called hyperplastic polyp, but evidence exists that have precancerous potential through serrated neoplasia pathway • It has high growth rate, and has similar risk of developing colorectal cancer as TA • Optimal treatment is complete endoscopic removal and probably managed as conventional adenoma
