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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.

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Presentation on theme: "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."— Presentation transcript:

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. SIAPEC-IAP Firenze 7-9 Settembre 2009 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.

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 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 HERCEP-TESTCEP17 3 HT 3+18 (17%)44 (16.35%) HT 2+72 (68%)143 (53%) HT 0/1+16 (15%)82 (30%) TOT POLYSOMY VERSUS HERCEP-TEST p= by x 2 Test SIAPEC-IAP Firenze 7-9 Settembre 2009

8 SIAPEC-IAP Firenze 7-9 Settembre 2009

9 FISHCEP17 3 HER2/Neu Amplificated16/114 (12.3%) HER2/Neu Not Amplificated98/114 (85.9) POLYSOMY VERSUS HER2/Neu STATUS SIAPEC-IAP Firenze 7-9 Settembre 2009

10 FISH VERSUS GRADING G1G2G3 HER2/Neu Amplificated 1(2%)13(27%)34(70.8) HER2/Neu Not Amplificated 13(0.4%)127(39.9)178(55.9%) TOT SIAPEC-IAP Firenze 7-9 Settembre 2009 p= by x 2 Test

11 HER2/Neu status and CEP17 status G1G2G3 Her2/Neu Amplif. and CEP (0%)1(0.8%)15(13.2%) Her2/Neu Amplif. and CEP (2.6%)27(23.7%)57 (50%) CEP17 with HER2/Neu Amplification versus Grading SIAPEC-IAP Firenze 7-9 Settembre 2009 p= by x 2 Test

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

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

14 Sample n°3: 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. SIAPEC-IAP Firenze 7-9 Settembre 2009 References: Salido M. et al, Brest Cancer Res 2005, 7: R267- R273 Hofmann M. et al, J. Clin. Pathol. 2008; 61; 89-94


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