Presentazione Fatta presso l'Ospedale della Marmara University ad Istanbul per l'esame di Anatomia Patologica. E' stato preso uno studio proveniente dall'Università degli Studi di Palermo. Il presentatore è Salvatore Zichichi. Esame conclusivo del periodo passato seguendo i casi in materia.

2. Advanced Gastric Cancer
is one of
the most prevalent and lethal
cancers worldwide;
989.602 new cases;
737.419 Dead;
represents the second and the
fourth leading cause of cancer
death in the world. No important
if female or male.

3. Trastuzumab for Advanced Gastric
Cancer(ToGA) – The Lancet 2010

4. ToGA
• 122 centers;
• 24 countries
• One Mission: Find overall survival in all
randomised patients who received study
medication at least once;

5. ToGa Result
on 594 patients
26% reduction in the risk of mortality;
Trastuzumab in combination with chemotherapy
can be considered as a new standard option for
patients with HER2-positive;

6. About ToGA
Thanks to this large study, it arrived to verify the
input data and observe the incidence in other
territories;
Different universities, including that of Palermo.
Participating in this new research based on
observation retrospective.

7. Sicily
Today, no data with regard to the HER2 status in AGCs are available
from the geographical area of a Mediterranean region;
This study analyzed 304 surgical cases of advanced/metastatic;
obtained from the archives of 10 Sicilian anatomopathological units;
the comparison between 1993-1995 and 2003-2005, independently
from the gender of patients;
Verify positive rate: HER2 into consideration histotype, grade, stage
and Ki-67 expression.

8. Ornek
Post-operative mortality excluded of the study (30 days
within of surgery);
No medical intervent;
All informed conses obtained of the patients;
Local Ethics Committees approval this study;
Mix Woman-Man;
Age range, 41-93 years (mean age 68.3);
Tumor localizated in the antrum, body, fundus,
gastroesophageal junction ;

9. Istological Type Detected
183 Tubolar/papillar/mucinous
adenocarcinomas (PTM);
98 poorly cohesive carcinoma;
23 rare variant of adenocarcinoma:
14 hepatoid adenocarcinomas (HAC);
9 mitochondrion-rich adenocarcinomas (MRC);

10. HER2
Determination
specimens were fixed in 10% neutral
formalin for 24‐48 h and paraffin
embedded at 56 C;
The histotypes, according to the WHO
classification, grade and staging were
also available.
IHC;
FISH(when were considered equivocal):
was performed exclusively in three well-
trained anatomopathological institutions
Following Score
0 absent staining
1+ faint and discontinuous
membranous staining in
<10% of n.e.
2+ light to moderate lateral,
basolateral or complete
membranous staining in
>10% of n.e.
3+ strong, intense lateral,
basolateral or complete
staining in >10% of n.e.

11. Additional immunohistochemestry
hepatoid adenocarcinomas sample
tested using polyclonal rabbit anti-
human and and monoclonal mouse
anti-human hepatocyte;
mitochondrion-rich adenocarcinomas
samples exhibited a positive
immunostaining pattern that was
localized in the cellular supranuclear
region by mouse polyclonal anti-
human mitochondria antibody;

12. Result of Observation
in Sicily
Consideration, HER2-positive rate, a range of variability 7.69-21.7%, was
identified in the various anato- mopathological units, with a mean value of
17.43% ;
This latter rate was marginally lower than the mean HER2 positivity that has
been previously cited;
53 of 304 AGC cases, independently from the histotype;
consideration only the IHC studies that are available in the literature, which
have been performed on 3264 AGC samples
HER2-positive rate was 17.6% (range, 6.8‐34.0%), which is equivalent to the
result of the present study
a non‐significant variation in HER2 determination should be attributed to the
subjective interpretation.

13. Neoplastic elements of the poorly cohesive
histotype showing HER2 negativity (x400)
3,5% -MRC-
Light-moderate incomplete HER2 2+ staining was
appreciated in the tubular areas of the
adenocarcinomas (x400)
31,3% -HACs-
Strong intense complete and diffuse HER2 staining
was encountered in AGC at a lower magnification
(x150)
31,3% -HACs -
Neoplastic thrombi showing 3+ HER2 overexpression
(x400). AGC, advanced gastric carcinoma.
-Angiolymphatic-
Progressive increase in the oncoprotein
immunoreactivity was observed:

14. HER2 overexpression was
significantly associated with:
high grade;
advanced stage;
high Ki-67 LI value;

15. Eureka!
HER2 status may represent an additional
morphological parameter that is able to affect
the mortality of patients with gastric cancer;
is a possibility that HER2 overexpression in AGC
may emerge as an independent prognostic
parameter, this requires clinical oncological
outcomes that are currently unavailable for the
present casuistry.

16. Kesif!
According to the ToGA;
17,43% AGC show one over expression of HER2;
Plus Success of treatment with trastuzumab
associated with chemotherapy for AGC;

17. New Therapy? Probable!
further investigations that are jointly
performed by pathologists and
oncologists present within the
geographical area of the current
study should confirm that the
association between trastuzumab
and chemotherapy determines an
improvement in survival for patients
with AGC showing amplification or
overexpression of the HER2 protein.

18. Consideration About
Life Style
• Gastrointestinal Disorders;
• Blood and Lymphatic system
disordes;
• General, metabolic and other
disorders;

19. İlginiz için teşekkür ederim!

20. Trionfo della Morte