Adenoma serrato e polipi intestinali: nuovi aspetti e ... · « Inhibition of apoptosis characterises serrated polips, whereas loss of inhibition of proliferation is the mechanism

Adenoma serrato e polipi intestinali: nuovi aspetti e

implicazioni cliniche

Stefano Crippa

Istituto Cantonale di Patologia

Lugano, 7 marzo 2007

PolypSerrated

• Torlakovic et al. (1996) Serrated adenomatous polyposisin humans

• Longacre, Fenoglio-Preiser (1990) Mixed hyperplasticadenomatous polyps/serrated adenomas: a distinct form ofcolorectal neoplasia

• Urbanski et al. (1984) Mixed hyperplasticadenomatous polyps: an underdiagnosed entity.

• Cooper et al. (1979) Adenomatous and carcinomatouschanges within hyperplastic colonic epithelium

Serrated lesions pathway

Response to tissue injury Genetic mechanism(Kras, BRAF, MLH1…)

« The hyperplastic polip can be defined as a lesion causedby the inibition of programmed cell death or apoptosis »J. R. Jass (2004)

« Despite decades of research into the behaviour of adenoma, we still do not know which adenomas are aggressive »J. R. Jass (2004)

serrated neoplasia pathway

vs

APC pathway (Vogelstein)

« Inhibition of apoptosis characterises serrated polips, whereasloss of inhibition of proliferation is the mechanism underlyingtubular adenomas » J. R. Jass (2004)

serrated

villous

tubulo-villous

tubular

adenocarcinomaMSI-H

(Mucinous-poorly

differentiated)

normalmucosa

adenocarcinomaMSS

(Mucinous-poorly

differentiated)

metastasis(~85% of CRCsaneuploidy)

metastasis(~15% of CRCsaneuploidy)

Colon cancer stratification

Diagrammatic Representation of the Serrated Neoplasia Pathway

Proximal ColonNormal

Hyperplastic Polyp Hyperplastic Polyp

Serrated Adenoma

MSI-H carcinoma

MLH1 methylation

Proliferation

Mutation of TGF-B, IGF and BAX genes

K-ras Mutation BRAF Mutation

Growthfactor

P

P

P

P

PPP

GRBSOS RAS

OUT

Changes ingene expression

CyclicAMP

Nucleus

Cytoplasm

P

BRAF

MEK

ERK1 ERK2

Adenylatecyclase

Growthfactor

G-protein

G-protein-coupledreceptor

The RAS-RAF-MAPK signalling pathway

TyrosineKinase

receptor

P P

Clinical relevance

• Separate traditional hyperplastic polyp from sessile serratedadenoma which is truly a neoplastic lesion that can progress tocarcinoma

• 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 developingcolorectal cancer as TA

• Optimal treatment is complete endoscopic removal and probably managed as conventional adenoma