Original Article Impact of polysomy 17 on HER2 testing of ... · Original Article Impact of polysomy 17 on HER2 testing of invasive breast cancer patients ... the HER2/CEP17 ratio

Int J Clin Exp Pathol 2014;7(1):163-173www.ijcep.com /ISSN:1936-2625/IJCEP1310062

Original ArticleImpact of polysomy 17 on HER2 testing of invasive breast cancer patients

Yang Liu1*, Li Ma2*, Dequan Liu1, Zhibing Yang1, Chengang Yang3, Zaoxiu Hu3, Wenlin Chen1, Zhuangqing Yang1, Sijun Chen1, Zhuoni Zhang1

1Department of Breast Surgery, The Third Affiliated Hospital, Kunming Medical University, Yunnan, China; 2De-partment of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing, China; 3Department of Pathology, The Third Affiliated Hospital, Kunming Medical University, Yunnan, China. *Equal contributors.

Received October 27, 2013; Accepted December 12, 2013; Epub December 15, 2013; Published January 1, 2014

Abstract: Background: Current American Society of Clinical Oncology/College of American Pathologists guidelines define HER2-positive tumors as those with > 6 HER2 genes per nucleus or those with HER2/CEP17 (chromosome 17) ratio > 2.2. These guidelines are potentially contradictory in tumors with polysomy of chromosome 17. The cur-rent study was performed to determine the impact of polysomy 17 on the interpretation of HER2 testing of invasive breast carcinomas. Methods: Chromosome 17 copies and HER2 gene status were identified by fluorescent in situ hybridization in 384 cases with invasive breast cancer, and the corresponding HER2 expression was obtained by im-munohistochemistry stain. Results: The average CEP17 copy number for the group was 2.1 (range, 1.0-12.4). Forty-eight cases (13.8%, 48/348) were identified as chromosome 17 polysomy with CEP 17 copy number ≥ 3. Ninety-two (26.4%) cases had > 6 copies of HER2 per nucleus, and 92 cases (26.4%) qualified as HER2 gene amplified using the HER2/CEP17 ratio (> 2.2) guideline. Polysomy 17 showed poorly positive correlations with both HER2 gene copy number and HER2 overexpression (P < 0.01, r = 0.338 and 0.271, respectively). The distribution of clinicopathologic parameters of Polysomy 17 tumors was more similar to HER2 negative than HER2 positive tumors. Conclusions: Polysomy 17 is a crucial cause of equivocal HER2 testing results by FISH, depending on which criterion (ratio vs. absolute number) is used for interpretation. Polysomy 17 cannot be an independent predictive factor for HER2 gene amplification or protein overexpression.

Keywords: Chromosome 17, polysomy, breast cancer, human epidermal growth factor receptor (HER2), fluores-cence in situ hybridization (FISH), immunohistochemistry (IHC)

Introduction

Accurate detection of the human epidermal growth factor receptor 2 (HER2/neu) altera-tions in tumors is crucial for assessing patient prognosis, predicting the response to standard chemotherapy, and determining the eligibility for HER2-tailored therapies [1]. According to the recently updated ASCO/CAP guidelines, HER2 testing is currently performed either by immunohistochemical assessment of HER2 protein, or by fluorescence in situ hybridization (FISH) analysis and by chromogenic in situ hybridization (CISH) of the HER2 gene [2, 3]. FISH assay is considered the gold-standard approach for patients with early or advanced breast cancer disease.

Previous studies have showed that FISH can be performed with single- or dual-colour probes. According to the scoring guidelines of ASCO/CAP recommendations [2], when using dual-colour FISH assays, HER2 gene amplification is defined relative to the number of signals for the chromosome 17 centromere (CEP17), with a ratio of > 2.2 qualifying for gene amplification. When using single-color FISH assay, HER2 gene amplification is considered as HER2 gene sig-nals > 6 per nucleus. These guidelines are potentially contradictory in tumors with polyso-my of chromosome 17. Obviously, chromosome 17 centromere copies may influence the final result explanation, especially in chromosome 17 polysomy cases with corresponding HER2 gene copies more than 6. Previously, it is report-

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HER2 gene status and chromosome 17 copies in breast cancer

164 Int J Clin Exp Pathol 2014;7(1):163-173

ed that polysomy 17 is a common event in breast cancer, about 5% to 50% [4, 5], but recently, Marchio et al reported the unexpected finding that true chromosome 17 polysomy is a very rare event in breast cancer (CEP17 copy number > 3.0), which is less than 10% [6]. Some reports also suspected that chromo-some 17 copies may predict HER2 gene status and the effect of HER2-tailored therapy in breast cancer patients [7, 8]. However, the exact effect of polysomy 17 and HER2 amplifi-cation remains controversial, and the clinical pathological characteristics of polysomy 17 cases are also unclear.

In the present study, we prospectively analyzed the HER2 status by the FISH assay and HER2

expression by IHC in a cohort of 348 patients with invasive breast cancer. We analyzed the exact effect of polysomy 17 and HER2 amplifi-cation, and indicated the clinical pathological characteristics of polysomy 17 cases.

Patients and methods

Patient samples

This study prospectively collected 348 tumor samples with invasive breast cancer from Department of breast surgery of the Third Affiliated Hospital of Kunming Medical University between November 2011 and March 2013. The study obtained a sufficient number of tumors qualified for HER2 testing in all cases. They had been detected for HER2 protein expression with IHC staining and for HER2 gene status with FISH analysis. The study involving human subjects has been in accord with the ethical standards established by the Local Commission for Medical Ethics and Clinical Studies (the Institutional Review Board (IRB) in Kunming Medical University), and in accord with the Helsinki Declaration.

Methods

Immunohistochemistry staining for HER2 expression: Each of invasive breast cancer tissue samples was fixed immediately in 10% neutral buffered formalin for 6 h - 48 h, and paraffin-embedded after operation. Immunostainings were run as described previously. The tumor tissue sections at 4 µm were routinely deparaf-finized, rehydrated and retrieved. HER2 protein expression was detected using polyclonal anti-body A0485 (DakoCytomation, Glostrup, Den- mark) at a dilution of 1:300 overnight at 4°C. Both positive and negative controls were used simultaneously with the test sample. According to ASCO/CAP guidelines, HER2 protein expres-sion was scored as follows: 0, no staining; 1+, weak and incomplete membrane staining in > 10% of the tumor cells; 2+, weak to moderate, complete membrane staining in > 10% of the tumor cells; and 3+, strong, complete mem-brane staining in > 30% of the tumor cells [3].

FISH analysis of the HER2 gene amplification: Commercially available FISH assays were done using the HER2 PathVysion FISH assay (Abbott Laboratories) as described elsewhere [9]. The kit consisted of a mixture of Spectrum Orange

Table 1. Clinicopathologic Characteristics of Patients (N = 348)Subject’s characteristics No. of subjects %Age (years) ≤ 50 years 180 51.7 > 50 years 168 48.3Tumor stage I 84 24.1 II 165 47.4 III 107 30.7 IV 2 0.6Tumor size (cm) < 2 cm 102 29.3 ≥ 2 cm, < 5 cm 228 65.5 ≥ 5 cm 18 5.2Menopause status Premenopause 178 51.1 Postmenopause 170 48.9ER status (cut-off ≥ 1%) ER+ 240 69.0 ER- 108 31.0PR status (cut-off ≥ 1%) PR+ 214 61.5 PR- 134 38.5Number of Lymph node 0 146 42.0 ≥ 1, < 4 108 31.0 ≥ 4 94 27.0HER-2 status on IHC 0/1+ 151 43.4 2+ 110 31.6 3+ 87 25.0



labeled HER2 gene probes and Spectrum Green labeled centromere controls for chromo-some 17 (CEP17). The HER2 and CEP17 signals in 30 randomly selected invasive cell nuclei in each of two separate distinct microscopic areas were examined in a blinded manner. Mean numbers of HER2 copies and CEP17 per nucleus were calculated. The tumor regions in every slide were selected by a licensed clinical laboratory scientist and confirmed by a board-certified pathologist. A new automatic system was used to analyze HER2 FISH samples with digital microscopy, called the slide scanning -platform Metafer PV (MetaSystems, Altluss- heim, Germany). Mean numbers of HER2 cop-ies and CEP17 per nucleus were calculated automatically. Polysomy 17 was defined as the occurrence of three or more copy numbers of centromeres for chromosome 17 per cell, according to Salido et al [10]. According to ASCO/CAP guideline, HER2 gene amplification was defined as HER2/CEP17 ratio ≥ 2.0 or HER2 signals per nuclei > 6 [3].

Statistical methods

Statistical analyses were performed using SPSS software, version 17.0 (SPSS Inc., Chicago, IL). Significant associations between aberrations of CEP17 copy number, HER2 sta-tus, and clinicopathologic characteristics were determined using 2-sided Fisher exact test. In addition, differences in clinicopathologic vari-ables between subgroups were checked using χ2 tests. The correlation between the HER2 copy number, the IHC score of HER2 protein and the polysomy 17 was assessed using Spe- arman rank correlation coefficient. A P-value < 0.05 was considered statistically significant.

Results

Patient data and clinical characteristics

Of 348 invasive breast cancer patients ana-lyzed in the present study, the clinicopathologic characteristics of patients with invasive breast carcinoma are presented in Table 1. Mean age

Figure 1. HER2 protein expression detected by IHC. A: Negative (score 0). B: Negative (score 1+). C: Equivocal (score 2+). D: Positive (score 3+).



was 51 years (range 19-84). Two hundred and two carcinomas (58.0%) were node negative, 146 (42.0%) had nodal involvement. Of all patients, 240 (69.0%) were ER positive, and 214 (61.5%) were negative. The representative images of HER2 assays in the present study are presented in Figure 1. A total of 87 (25.0%) specimens were positive and scored 3+ by IHC test (Figure 1D), while 151 (43.4%) specimens were negative and scored 0 and 1+ (Figure 1A, 1B). The remaining 110 specimens (31.6%) were scored 2+ (Figure 1C) and were thus con-sidered as equivocal in Table 2.

Comparison between IHC and FISH for HER2 status

Comparison between IHC and FISH for HER2 testing is outlined in Tables 2 and 3 with differ-ent FISH criteria for HER2 status. Figures 1 and 2 show the HER2 protein and gene expression in breast cancer. The average CEP17 copy num-ber for the group was 2.1 (range, 1.0-12.4) (Figure 3). Fourty-eight cases (13.8%, 48/348) were identified as chromosome 17 polysomy with CEP 17 copy number ≥ 3. Ninety-two (26.4%) cases had > 6 copies of HER2 per nucleus, and 92 cases (26.4%) qualified as HER2 gene amplified using the HER2/CEP17 ratio (> 2.2) guideline. An equivocal HER2 sta-tus by FISH was found in 8 (2.3%) of 348 patients based on absolute HER2 gene copy

number and in 11 (3.2%) of 348 patients based on the ratio HER2/CEP17. Remarkably, none of these patients showed HER2 overexpression on IHC (score 3+). Most of patients with an equivocal HER2 status by FISH displayed poly-somy 17. Of IHC score 2+ cases, approximately 85% cases showed HER2 gene non-amplifica-tion by FISH, but of FISH HER2 equivocal cases, about 100% cases indicated equivocal HER2 status or negative. HER2 overexpression was significantly associated with HER2 gene num-ber (r = 0.719, p < 0.001) and HER2/CEP17 (r = 0.739, p < 0.001). Note that there was a poor correlation between polysomy 17 and HER2 expression (r = 0.271, p < 0.001), HER2 gene copies (r = 0.338, p < 0.001). Figure 4 shows the distribution of mean number of HER2/cen-tromere 17 ratio, in which 44.1% cases were 2-2.99.

Impact of polysomy 17 on HER2 status by IHC and FISH

Polysomy 17 was observed in 48 (12.4%) of 348 patients, either on its own (15/48), in com-bination with HER2 gene equivocal status (4/48), or in combination with HER2 gene amplification (29/48). As shown in Table 4, among the polysomy 17 cases with HER2 over-expression by IHC (score 3+), most cases (24/26) showed HER2 gene amplification. In contrast, of polysomy 17 cases with HER2 non-

Table 2. Comparison between IHC and FISH for Determination of HER2 StatusFISH

Positive Equivocal NegativeIHC HER2 > 6 % 4 ≤ HER2 ≤ 6 % HER2 < 4 % TotalPositive, 3+ 80 92.0 0 0.0 7 8.0 87Equivocal, 2+ 9 80.9 6 5.5 95 86.4 110Negative, 0/1+ 3 2.0 2 1.3 146 96.7 151Total 92 26.4 8 2.3 248 71.3 348

Table 3. Comparison between IHC and FISH for Determination of HER2 statusFISH

Positive Equivocal NegativeIHC R* > 2.2 % 1.8 ≤ R ≤ 2.2 % R < 1.8 % TotalPositive, 3+ 80 88.5 0 0.0 7 8.0 87Equivocal, 2+ 11 9.1 8 7.3 91 82.7 110Negative, 0/1+ 1 0.7 3 2.0 147 97.3 151Total 92 25.3 11 3.2 245 71.5 348*The ratio of HER2/chromosome 17 copy number (R).



overexpression, all cases did not show HER2 amplification. In HER2 non-amplification patients, 5.6% (13/245) had polysomy 17,

94.7% (232/245) did not have polysomy 17. Interestingly, three patients showed a relatively high increase in HER2 gene copy number as a

Figure 2. HER2 detection using Metafer PV (MetaSystems, Altlussheim, Germany). A: Carl Zeiss AG microscope. B: HER2 non-amplification. C: HER2 amplification.



result of polysomy 17 (6-7 copies) and were interpreted as positive based on absolute HER2 gene copy number. But according to the HER2/CEP17 ratio, however, three of these patient cases were interpreted as HER2 nega-tive (ratio 6/4, 7/6, 7/5, all < 1.8), whereas two patient cases were in the equivocal range (ratio 8/4 and 10/5, both = 2.0). These data illustrate how polysomy 17 can be interpreted as HER2 positive or HER2 negative, partly depending on which scoring method is applied to interpret HER2 FISH results.

Clinicopathologic characteristics of polysomy 17 tumors

The distribution of clinicopathologic parame-ters in HER2 negative, polysomy 17, and HER2 positive tumors were shown in Table 5. Compared with HER2 negative tumors, HER2 positive tumors showed higher clinical stage (P = 0.039), higher tumor stage (P < 0.001) and were more frequently ER negative (P < 0.001) and PR negative (P < 0.001). Polysomy 17 tumors were more similar to HER2 negative

Figure 3. HER2 gene status identified by FISH. A: HER2 gene non-amplification without polysomy 17. B: HER2 gene amplification with polysomy 17. C: HER2 gene non-amplification without polysomy 17. D: HER2 gene amplification with polysomy.



than HER2 positive tumors. Although tumor grade (P = 0.041), ER status (P < 0.001), and PR status (P < 0.001) differed significantly between polysomy 17 tumors and HER2 posi-tive tumors, no differences were found between polysomy 17 tumors and HER2 negative tumors in any of the clinicopathologic parameters investigated.

Discussion

This study aimed to investigate the frequency of Polysomy 17 and its association with HER2 alterations in invasive breast cancer patients by FISH and IHC analysis. Also, we determined the clinical pathological characteristics in Polysomy 17 patients.

The potential for such misinterpretations is that polysomy 17 is relatively common in breast car-cinomas. In a recently published series by Vanden et al, > 40% of breast carcinomas were found to harbor increased CEP17 copy number [11]. However, recent validation studies per-formed via comparative genomic hybridization have shown that “true” polysomy 17 is a rare event and that CEP17 amplification can mimic the presence of multiple copies of chromosome 17, leading to an overestimation of the inci-dence of polysomy 17, as confirmed in our study [12]. In our series, polysomy 17, defined as three or more chromosome copies, was reported in about 13.8% of invasive breast can-cer by FISH analysis, following ASCO/CAP guide-lines, which suggested that standard detection method and diagnosis criterion maybe critical for accurate detection of polysomy 17. In addi-tion, HER2 gene is located on chromosome 17, and CEP 17 copy number is used to evaluate

the amplification of chromosome 17. Therefore, CEP17 copy number rep-resents an important source of inac-curacy in FISH testing for HER2 amplification.

Our study indicates that determina-tion of HER2 amplification status may partly depend on whether CEP17 copy number was taken into account. Indeed, almost 23% of the studied cases harboring > 6 copies of the HER2 gene did not show HER2 gene amplification (ratio > 2.2). Importantly, a majority of these cases had a borderline score (2+) on IHC, and more than 85% of patients

Figure 4. Distribution of mean number of HER2/centromere 17 ratio.

with IHC 2+ showed HER2 negative by FISH analysis. Therefore, these cases were not ame-nable for anti-HER2 targeted therapy and did not fit with the HER2 amplification breast carci-noma category.

Notably, the value of the effect of polysomy 17 on HER2 alteration in breast cancer is contro-versial. Some studies showed that polysomy 17 alone might not significantly contribute to the variation in HER2 copy number and HER2 pro-tein overexpression [13-15]. However, Sneige et al concluded that the copy number of chro-mosome 17 was associated with an increased level of HER2 protein but not with HER2 ampli-fication [16]. Other authors found that the fre-quency of polysomy 17 was higher in IHC 3+/ nonamplified tumors than in IHC 0/1+/2+/non-amplifiedones and that the mean chromosome 17 copy number increased with IHC scoring in these nonamplified tumors [17-19]. Based on our experience, we would suggest that the HER2 amplification and chromosome 17 poly-somy should be recorded simultaneously in the pathologic report. We found that there was a poor correlation between polysomy 17 and HER2 protein overexpression (r = 0.223, p < 0.001), HER2 gene copies (r = 0.271, p < 0.001). In addition, our data showed that poly-somy 17 influenced the HER2 protein expres-sion in IHC 2+ or FISH equivocal tumors. For example, 12.7% (14) of 110 tumors with IHC 2+ score had polysomy 17, more than that those cases with IHC 0/1+, and 100% (11) of 11 tumors with FISH equivocal status had polyso-my 17, more than that those cases with HER2 non-amplification or amplification. In addition, the frequency of cases that had both polysomy



Table 4. Correlation between HER2 protein expression and chromosome 17 polysomyChromosome 17 polysomy

Present (n = 48) % Absent (n = 300) % Total r PIHC 0.271 0.000 3+ 26 30.0 61 70.0 87 2+ 14 12.7 96 87.3 110 0/1+ 8 5.3 143 94.7 151FISH 0.390 0.000 R* > 2.2 29 31.5 63 68.5 92 1.8 ≤ R ≤ 2.2 8 72.7 4 43.0 11 R < 1.8 11 4.5 234 95.5 245FISH 0.223 0.000 HER2 > 6 31 33.7 61 66.3 92 4 ≤ HER2 ≤ 6 7 87.5 1 12.5 8 HER2 < 4 10 4.0 238 96.0 248*The ratio of HER2/chromosome 17 copy number (R).

Table 5. Distribution of Clinicopathologic Features in Polysomy 17 Tumors Compared With HER2 Negative and HER2 Positive Tumors identified by R

HER2 Negative(n = 230)

Polysomy 17(n = 48)

HER2 Positive(n = 63)

Characteristic No. % P* No. % P† No. % P‡

Age (years) 0.850 0.863 0.982 ≤ 50 years 118 51.3 24 50 35 55.6 > 50 years 112 48.7 24 50 28 44.4Tumor stage 0.542 0.041 0.000 I 56 24.4 7 20.8 10 15.9 II 110 47.8 27 41.7 19 30.2 III 64 27.8 13 35.4 33 52.4 IV 0 0 1 2.1 1 1.6Tumor size (cm) 0.080 0.223 0.961 < 2 cm 71 30.9 9 18.8 20 31.7 ≥ 2 cm, <5 cm 149 64.8 34 70.8 40 63.5 ≥ 5 cm 10 4.29 5 10.4 3 4.8Histological grade 0.127 0.945 0.039 Well differentiated 24 10.4 1 2.1 1 1.6 Moderate differentiated 146 63.5 30 62.5 40 63.5 Poor differentiated 60 26.1 17 35.4 22 34.9Menopause status 0.328 0.322 0.800 Premenopause 119 51.7 21 43.8 33 52.4 Postmenopause 111 48.3 27 56.2 30 47.6ER status 0.253 0.016 0.000 ER+ 172 74.8 32 66.7 27 42.9 ER- 58 25.2 16 33.3 36 57.1PR status 0.894 0.003 0.000 PR+ 152 66.1 32 66.7 24 38.1 PR- 78 34.9 16 33.3 39 61.9LNM 0.228 0.591 0.651



17 and HER2 amplification (50.0%) was higher than that (27.1%) of those that had polysomy 17 without HER2 amplification (P < 0.001). Therefore, we concluded that HER2 gene ampli-fication or protein overexpression may partially contribute to polysomy 17 in tumors but poly-somy 17 cannot predict HER2 status itself.

Interestingly, there is another issue of clinical relevance that whether Polysomy 17 is associ-ated with a clinical behavior similar to that of

HER2 amplified tumors. Many previous data suggest that the presence of CEP17 alterations could identify a subset of breast cancers with more aggressive biological and clinical behav-ior, which may show non-responsiveness to conventional therapy independently of HER2 amplification status [20-23]. Bartlett et al in a recent study showed that the presence of poly-somy 17, as established by CEP17 FISH, was predictive of response to anthracyclines [24]. This further underlines the importance of

0 100 43.5 20 41.7 24 38.1 ≥ 1, < 4 73 31.7 11 22.9 21 33.3 ≥ 4 57 24.8 17 35.4 18 28.6HER2 status on IHC 0.000 0.000 0.000 0/1+ 141 61.3 8 16.7 1 1.6 2+ 83 36.1 14 29.2 7 11.1 3+ 6 2.6 26 54.1 55 87.3Ki status 0.866 0.775 0.569 Positive 38 16.5 9 18.8 14 22.2 Negative 180 78.3 38 79.2 45 71.5 Unknown 12 5.2 1 2.0 4 6.3P53 status 0.002 0.790 0.003 Positvie 46 20.0 20 41.7 27 42.9 Negative 182 79.1 27 56.3 36 57.1 Unknown 2 0.9 1 2.0 0 0CEA (cutoff 5 μg/ml) 0.546 0.573 0.120 Positive 5 2.2 2 4.2 5 7.9 Negative 225 97.8 46 95.8 58 92.1CA125 (cutoff 35 μg/ml) 0.803 0.110 0.146 Positive 8 3.5 2 4.2 1 1.6 Negative 222 96.5 46 95.8 62 98.4CA153 (cutoff 25 μg/ml) 0.179 0.484 0.692 Positive 9 3.9 4 8.3 3 4.8 Negative 221 96.1 44 91.7 60 95.2TPS (cutoff 100 U/l) 0.620 0.635 0.943 Positive 24 10.4 5 10.4 10 15.9 Negative 83 36.1 22 45.8 26 41.3 Unknown 123 53.5 21 43.8 27 42.9CK5/6 0.113 0.149 0.684 Positive 12 5.2 5 10.4 2 3.2 Negative 89 38.7 15 31.3 23 36.5 Unknown 129 56.1 28 58.3 38 60.3TOP2A 0.107 0.524 0.418 Positive 87 37.8 24 50.0 34 54.0 Negative 123 53.5 20 41.7 26 41.3 Unknown 20 8.7 4 8.3 3 4.7*HER-2 negative versus polysomy 17. †Polysomy 17 versus HER-2 positive. ‡HER-2 positive versus HER-2 negative.



assessing chromosome 17 copy number increase for investigating the possible implica-tion in the clinical management of patients with Chromosome 17 copy number gain. A recently published data suggested that the presence of CEP17 alterations could identify a subset of breast cancers with more aggressive biological and clinical behavior, which may show nonre-sponsiveness to conventional therapy indepen-dently of HER2/neu amplification status [25]. And Moelans et al showed that Chromosome 17 polysomy without HER2 amplification does not predict response to lapatinib in metastatic breast cancer [26]. Our finding suggested that the clinicopathologic impact of CEP17 altera-tion is not as strong as that of HER2 gene amplification and show that polysomic tumors possess pathologic features more similar to HER2 negative than to HER2 positive tumors. It is likely that long term studies are required to point out an independent prognostic role or clinical response to trastuzumab of polysomy 17.

In summary, polysomy 17 is a crucial cause of equivocal HER2 testing results by FISH, depend-ing on which criterion (ratio vs. absolute num-ber) is used for interpretation. We provide evi-dence that the polysomy of chromosome 17 cannot be an independent predictive factor for HER2 gene amplification or protein overexpres-sion in invasive breast cancer. Determining what CEP17 amplification means in terms of response to trastuzumab and anthracyclin treatments remains to be further studied.

Acknowledgements

We would like to thank all patients in our study. We are indebted to Mr. Muhammad Jabran for his careful English assistance during the prepa-ration of the manuscript. This work was sup-ported by Society Science and Technology Development Program Fund of Yunnan Province (2009ZC118M), Joint special fund of Science and Technology Department of Yunnan Province (2010CD184).

Disclosure of conflict of interest

None.

Address correspondence to: Dr. Dequan Liu, Department of Breast Surgery, The Third Affiliated Hospital, Kunming Medical University, No. 519

Kunzhou Road, Xishan District, Kunming City, Yunnan, China. Tel: +86-871-8185656; Fax: +86-871-8185656; E-mail: [email protected]

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Original Article Impact of polysomy 17 on HER2 testing of ... · Original Article Impact of polysomy 17 on HER2 testing of invasive breast cancer patients ... the HER2/CEP17 ratio