CHROMOSOME 17 POLYSOMY ON
HER2/Neu STATUS IN BREAST CANCER
S. Petroni, T. Addati, M.A. Caponio, V. Rubini, M.
Asselti, G. Giannone, F. Palma, G. Simone
IRCCS – Istituto Tumori “Giovanni Paolo II”
UO Anatomia Patologica
SIAPEC-IAP Firenze
7-9 Settembre 2009
INTRODUCTION:
Chromosome 17 (Ch17polysomy ) is
often found in breast cancer and may
complicate the interpretation of HER2
testing results.
SIAPEC-IAP Firenze
7-9 Settembre 2009
The aim of the study was to analyze:
•
HER2 amplification in tumors where HER2 status
was scored as 2+ (Dako) on Immunohistochemistry
(IHC);
•
the prevalence of polysomy17, defined as ≥3 copies
of the chromosome and its correlation with HER2
protein expression and gene amplification;
•
the correlation of polysomy with biological and
pathological features as compared with tumors
HER2 amplified.
SIAPEC-IAP Firenze
7-9 Settembre 2009
MATERIAL AND METHODS:
428 cases of invasive breast cancer entered the
study.
327
cases with weakly or moderate positive staining
for HER2 on IHC (0/1+/2+) where selected.
The following methods
recommended protocol :
applied according to the

Overexpression: Immunohystochemical staining,
using polyclonal antibody A0485.

Amplification: FISH analysis (Vysis).
HER2 gene amplification: average ratio ≥2.2.
SIAPEC-IAP Firenze
7-9 Settembre 2009
RESULTS 1:
Ch17Polysomy was observed in 114/428 cases (26.7%).
In 106 of those (24.7%) the overexpression by IHC using
HercepTest was evaluated: 72 (67.9%) were scored
HER2 2+,18 (16.9%) 3+,16 as 0/1+ (p=0.007).
HER2 gene amplification was detected in 16 out off 114
polysomic cases (14%) enclosing 12 overespressed
(3+) and 4 scored as( 2+).
One only case showed an histological low grade (G1).
Nodal status (328 evaluable cases): 158 were N0 and
170 N+: polysomy was detected in 39 (24%) and 53
(31.3%) cases,respectively.
SIAPEC-IAP Firenze
7-9 Settembre 2009
RISULTS 2:
Hormone Receptor and kinetic activity were
evaluable in 110 cases.
78 tumors (71%) resulted ER+/PgR+ and 20
ER-/PgR- (18%);
76 tumors (69%) showed high MIB1 (Cut off:
20%).
SIAPEC-IAP Firenze
7-9 Settembre 2009
POLYSOMY VERSUS HERCEP-TEST
HERCEP-TEST CEP17 ≥ 3
CEP17 ≤ 3
HT 3+
18 (17%)
44 (16.35%)
HT 2+
72 (68%)
143 (53%)
HT 0/1+
16 (15%)
82 (30%)
TOT.
106
269
p= 0.007 by x2 Test
SIAPEC-IAP Firenze
7-9 Settembre 2009
Polysomy versus Hercep-Test
HT 0/1+
15%
HT 3+
17%
HT 2+
68%
HT 3+
HT 2+
HT 0/1+
SIAPEC-IAP Firenze
7-9 Settembre 2009
POLYSOMY VERSUS HER2/Neu STATUS
FISH
HER2/Neu
Amplificated
HER2/Neu
Not Amplificated
CEP17 ≥ 3
16/114 (12.3%)
98/114 (85.9)
SIAPEC-IAP Firenze
7-9 Settembre 2009
FISH VERSUS GRADING
HER2/Neu
Amplificated
HER2/Neu
Not
Amplificated
TOT.
p= 0.074 by x2 Test
G1
G2
G3
1(2%)
13(27%)
34(70.8)
13(0.4%) 127(39.9)
14
140
178(55.9%)
212
SIAPEC-IAP Firenze
7-9 Settembre 2009
CEP17 with HER2/Neu Amplification versus Grading
HER2/Neu status and
CEP17 status
G1
G2
G3
Her2/Neu Amplif.
and CEP17 ≥ 3
0 (0%)
1(0.8%)
15(13.2%)
Her2/Neu Amplif.
and CEP17 ≤ 3
3 (2.6%)
27(23.7%) 57 (50%)
p= 0.049 by x2 Test
SIAPEC-IAP Firenze
7-9 Settembre 2009
Sample n°1:
HER2/Neu (IHC) 2+
Sample n°1: Amplificated
Gene and Ch17 Polysomy
SIAPEC-IAP Firenze
7-9 Settembre 2009
Sample n°2:
HER2/Neu (IHC) 2+
Sample n°2: Amplificated
Gene and moderate Ch17
Polysomy
SIAPEC-IAP Firenze
7-9 Settembre 2009
Sample n°3:
HER2/Neu (IHC) 2+
Sample n°3: Amplificated
Gene and Ch17 Polysomy
SIAPEC-IAP Firenze
7-9 Settembre 2009
CONCLUSIONS:
Ch17Polysomy showed high incidence both in HER2
not amplified and not overexpressed cases and
confirming that HER2 gene
amplification/overexpression is indipendent from
Polysomy17.
High incidence of polysomic cases in tumor 2+ (IHC)
lead to the hypothesis that this subgroup could
benefit by target therapy.
References:
•Salido M. et al, Brest Cancer Res 2005, 7: R267R273
•Hofmann M. et al, J. Clin. Pathol. 2008; 61; 89-94
SIAPEC-IAP Firenze
7-9 Settembre 2009