1. 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

2. 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

3. 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

4. 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 applied according to the recommended protocol :
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

5. 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

6. Hormone Receptor and kinetic activity were evaluable in 110 cases.
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

7. 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= by x2 Test
SIAPEC-IAP Firenze
7-9 Settembre 2009

8. SIAPEC-IAP Firenze
7-9 Settembre 2009

9. POLYSOMY VERSUS HER2/Neu STATUS FISH CEP17 ≥ 3 HER2/Neu Amplificated
16/114 (12.3%)
Not Amplificated
98/114 (85.9)
SIAPEC-IAP Firenze
7-9 Settembre 2009

10. FISH VERSUS GRADING G1 G2 G3 HER2/Neu Amplificated 1(2%) 13(27%)
34(70.8)
HER2/Neu
Not Amplificated
13(0.4%)
127(39.9)
178(55.9%)
TOT. 14
140
212
p= by x2 Test
SIAPEC-IAP Firenze
7-9 Settembre 2009

11. 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= by x2 Test
SIAPEC-IAP Firenze
7-9 Settembre 2009

12. Sample n°1: Amplificated Gene and Ch17 Polysomy
HER2/Neu (IHC) 2+
Sample n°1: Amplificated Gene and Ch17 Polysomy
SIAPEC-IAP Firenze
7-9 Settembre 2009

13. Sample n°2: Amplificated Gene and moderate Ch17 Polysomy
HER2/Neu (IHC) 2+
Sample n°2: Amplificated Gene and moderate Ch17 Polysomy
SIAPEC-IAP Firenze
7-9 Settembre 2009

14. Sample n°3: Amplificated Gene and Ch17 Polysomy
HER2/Neu (IHC) 2+
Sample n°3: Amplificated Gene and Ch17 Polysomy
SIAPEC-IAP Firenze
7-9 Settembre 2009

15. 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: R267-R273
Hofmann M. et al, J. Clin. Pathol. 2008; 61; 89-94
SIAPEC-IAP Firenze
7-9 Settembre 2009