Download Adenoma serrato e polipi intestinali: nuovi aspetti e implicazioni

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