Sabato 27 ottobre 2012 - Pacini Editore

RElaziONi
Le coliti croniche non IBD
V. Villanacci
Anatomia Patologica, Spedali Civili Brescia
La relazione considera i differenti aspetti istologici con cui
può manifestarsi una colite cronica non IBD con particolare
riferimento al danno da farmaci o allergico a livello colico in
modo tale da poter fornire al clinico, da parte del patologo,
una chiara indicazione in tal senso.
Vengono esaminate le differenti possibilità riguardanti la colite
linfocitica, la colite collagena e l’incremento del numero
dei granulociti eosinofili (valore superiore a 60 per 10 campi
di visione a 40x) nei segmenti del colon SX come espressione
di tale danno.
Ulteriore elemento e la diagnosi differenziale con differenti
entità in particolare le Malattie Infiammatorie Croniche Intestinali.
role of HEr2 in esophageal and gastric
carcinogenesis and reliability of its evaluation
in endoscopic biopsies.
L. Mastracci1 , M. Fassan2 , S. Pigozzi1 , S. Bruno1 , F. Grillo1 1 Department of Surgical and Diagnostic Sciences (DISC), Pathology
Unit, University of Genoa and IRCCS S. Martino-IST University
Hospital, Genoa, Italy; 2 Department of Medicine (DIMED), Surgical
Pathology & Cytopathology Unit, University of Padua, Padua, Italy
The human epidermal growth factor receptor 2 (HER2) protooncogene,
located on chromosome 17q21 1 , encodes for a
transmembrane tyrosine-kinase receptor. HER2 gene amplification
and HER2 protein overexpression have been identified
in various carcinomas, including breast, lung, ovarian,
endometrium, colon and gastro-esophageal cancer 2 3 . Several
studies have focused on HER2 status in gastric cancer, showing
HER2 positivity rates comprised between 10 and 30% 4 5 ;
on the other hand less data are available for esophageal and
junctional adenocarcinoma (ADC), where HER2 positivity
has been reported at approximately 20-25% 6 . Similarly to
breast cancer, HER2 overexpression and amplification in
gastric and esophageal ADC has been associated with poorer
prognosis and more aggressive disease 7 8 . Recently the ToGA
trial successfully applied anti-HER2 therapy (i.e. Trastuzumab)
in advanced gastro-esophageal cancers demonstrating a
significant survival advantage in the Trastuzumab group with
no significant increase in toxic side-effects 9 . These results led
to FDA and EMEA approval of the addition of trastuzumab to
fluoropyrimidine/platinum-based therapies in advanced HER2
positive gastro-esophageal cancer 10 .
Following the enthusiasm of these results in the treatment
of a cancer that is still one of the leading causes of cancerrelated
deaths worldwide, several studies have focused on
the prognostic and predictive value of HER-2 expression in
gastric and esophageal ADC. Furthermore several papers on
the methodology of HER detection (immunohistochemistry,
Venerdì, 26 ottobre 2012
Sala Caravaggio – 08.30-10.30
Patologia gastro-enterica 1
Moderatori: Roberto Fiocca (Genova), Luca Saragoni (Forlì)
209
fluorescence in situ hybridization – FISH, chromogenic in situ
hybridization – CISH) and the specific scoring system that has
to be applied for evaluation, have appeared in the literature.
Two different aspects however still deserve to be investigated:
1) the role of HER2 in esophago-gastric cancerogenesis and
2) the reliability of HER2 evaluation in endoscopic biopsies.
1) Role of HER2 in esophageal and gastric carcinogenesis
Esophageal and gastric development of ADC (intestinal-type
ADC of the stomach and ADC in Barrett’s esophagus) depends
on a multistep process in which the main causing factor
is represented by a longstanding inflammation resulting in the
replacement of native mucosa with metaplastic epithelium. In
this setting, intestinal metaplasia (IM) has been recognized as
the “carcinogenic field” in which neoplasia (intra-epithelial
neoplasia and invasive ADC) can develop 11-13 .
Few authors have focused their attention in exploring the
HER2 status in pre-neoplastic and/or pre-invasive lesions
and only fragmentary information is available in this setting.
Concerning the development of ADC arising in Barrett’s
esophagus, the group of Villanacci and Rossi, have shown in
several reports 14-16 that HER2 overexpression/amplification is
demonstrable in a high proportion of patients with dysplasia
and ADC. In particular two out of five low grade dysplasias
(LGD), four out of eight high grade dysplasias (HGD) and
five out of thirteen ADCs have shown amplification of HER2
by FISH, providing evidence for a possible role of HER2
in the transition from dysplasia to ADC of the esophagus.
On the other hand none (0/18) of the patients with Barrett’s
esophagus (BE) showed HER2 amplification. The same field
was explored by Hu and coll 17 who have studied a larger
group of ADCs (116 cases), pre-invasive (18 LGD and 15
HGD) and pre-neoplastic (34 BE) lesions as well as columnar
cell metaplasia (CCM – 81 cases) and squamous esophageal
epithelium (86 cases). HER2 amplification was found in only
one case (6.7%) of HGD and in 21 (18%) ADCs compared to
a complete negativity of all cases of LGD, CCM and BE. This
low rate of HER2 overexpression in pre-neoplastic lesions
may support the hypothesis that HER2 is involved in a late
stage of esophageal carcinogenesis.
Still less information is available for gastric carcinogenesis in
which only the study by Lee et al. 18 has focused on this topic,
showing HER2 positivity in 12,6% (nine out of 70 cases) of
gastric HGDs in comparison to 20,2% of invasive carcinomas.
The study was conducted analyzing both the pre-invasive and
invasive component of cancer in the same patient. In 6 cases
score 3+ immunoreactivity was identified in both dysplasia
and carcinoma, while in three cases HER2 overexpression/
amplification was limited to dysplastic epithelium and not
seen in the invasive component.
The exhaustive study by our group 19 has finally explored
the HER2 status in all the phenotypic alterations involved in
gastric and esophageal carcinogenesis and in a large number
of samples. Twenty five cases for each group were evaluated.
Cases with extensive intestinal metaplasia (IM) of the
distal gastric mucosa, LGD, HGD and intestinal type ADC