ABSTRACT
Objective@#To investigate the locoregional benefit from adjuvant anti-HER-2 target therapy and the possibility of omitting postmastectomy radiation therapy (PMRT) in HER-2 positive breast cancer patients.@*Methods@#Clinical data of 1398 patients diagnosed with HER-2+ breast cancer admitted to our hospital who underwent mastectomy without PMRT from 2009 to 2014 were retrospectively analyzed, and 370 of them received adjuvant anti-HER-2 target therapy mainly with trastuzumab.@*Results@#Anti-HER-2 target therapy significantly improved the disease-free survival (DFS) and overall survival (OS), whereas reduced the locoregional recurrence (LRR) insignificantly. Multivariate analysis demonstrated that anti-HER-2 target therapy improved the locoregional recurrence-free survival (LRRFS)(P=0.06). After propensity score matching, the 5-year LRR rate was 4.4% vs. 6.4%(P=0.070) for those treated with and without anti-HER-2 target therapy. Subgroup analysis revealed that the locoregional control benefit was only significant in patients with pathological Grade Ⅰ-Ⅱtumors (2.5% vs. 5.9%, P=0.046). For patients with pN1 tumors with and without anti-HER-2 target therapy, the 5-year LRR rate was 8.2% vs. 12.3%(P=0.150). Patients with hormone receptor-positive tumors obtained significant benefit from anti-HER-2 target therapy. The 5-year LRR rate could be less than 5% in patients with favorable risk factors who received anti-HER-2 target therapy.@*Conclusions@#Anti-HER-2 target therapy with trastuzumab can improve the LRRFS of patients with HER-2+ breast cancer after mastectomy. Nevertheless, patients with radiotherapy indications have to receive radiotherapy due to relatively high recurrence rate. Newly approved dual HER-2 blockade is a promising approach to further reduce LRR. Subgroup analysis is required to identify the low-risk patients.
ABSTRACT
@#Introduction: Evaluation of HER2 status in breast cancer using immunohistochemistry (IHC) and in-situ-hybridisation (ISH) study is important to establish prognosis and to select patient for targeted therapy. Objective: The study aims to determine the concordance between HER2 protein IHC score and its gene status by dual-colour dual-hapten in-situ-hybridization (DDISH) study. Materials and Methods: Retrospective study was performed on 767 referred breast cancer cases over a period of five years. The HER2 IHC score (the initial and repeat test score) and the results of HER2 gene status by DDISH were retrieved from the histopathological reports. The agreement between initial IHC score with repeat test score was measured using Cohen Kappa. Chi square test analyzed the association between HER2 IHC score with its gene status by DDISH. Results: The concordance of HER2 IHC score between the initial and repeat test were 52.7% and 89.4% for IHC score 2+ and 3+ respectively. There was moderate agreement of HER2 IHC score between the initial and repeat test score (κ = 0.526, p<0.001). A significant association noted between HER2 IHC score with its gene status by DDISH (p<0.001). Only 56 out of 207 cases (27.1%) with 2+ IHC score showed HER2 gene amplification while the majority of cases with 3+ IHC score were gene-amplified (446 out of 451, 98.9%). Conclusion: ISH study should be done in all IHC-equivocal cases (2+) to select patient for targeted therapy. Gene amplification must also be confirmed in IHC-positive cases (3+) to prevent from giving non-effective treatment with possible adverse effects to patient with nonamplified HER2 gene.
Subject(s)
Breast NeoplasmsABSTRACT
Objective To compare the differences and correlation between immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) of HER2 in invasive breast cancer.Methods A total of 604 breast cancer specimens from Nov.2014 to Dec.2016 in Renmin Hospital of Wuhan University were evaluated for HER2 status by both IHC and FISH to calculate the concordance between these two assays and analyze the causes of discordant cases.Results Except for cases with IHC uncertainty(2+),overall concordance between IHC and FISH in detection of HER2 was 97.2％ (412/424).The concordance for positive and negative detection was 93.0％(146/157) and 99.6％(266/267),respectively.The main reasons for the difference of HER2 expression in breast cancer detected by the two methods were the incorrect interpretation of IHC,the higher or lower concentration of antibody,and the change in guidelines.Conclusion HER2 IHC assay is subjective and sensitive to technical factors for determining the expression levels of HER2 protein in breast cancer so that it is not as stable as HER2 FISH assay.
ABSTRACT
Background and purpose:Pathogenic gene polymorphism may affect the function of gene, leading to the difference of individual tumor susceptibility and heterogeneity of bioactive substances in individuals. The purpose of this study was to investigate the interrelationship betweenHER-2 gene polymorphism and its protein expression, and to evaluate their association with the clinicopathological characteristics of breast cancer.Methods:The data from a total number of 303 female breast cancer patients of Han ethnicity were collected. The MassARRAY platform was used to examineHER-2 gene rs2517954 and rs2517955 single nucleotide polymorphisms. Meanwhile immunohistochemistry was used to detect HER-2 protein expression and corresponding estrogen receptor (ER), progesterone receptor (PR), P53 and Ki-67 expressions in breast cancer tissues. Pearson chi-square test was used to study the relationship of the two loci and the protein expression, and their correlation with clinicopathological features of breast cancer was analyzed.Results:Under the codominant model,HER-2 gene rs2517954 and rs2517955 loci polymorphisms were associated with its protein expression (χ2=9.613,P=0.008;χ2=9.613,P=0.008). And under the dominant model,HER-2 gene rs2517955 loci TT homozygous and CT heterozygous mutant was associated with its protein expression (χ2=8.894,P=0.003). There were no signiifcant correlations betweenHER-2 gene rs2517954, and rs2517955 loci polymorphisms, and breast cancer patients’ clinical stage, tumor size, histological grade, lymph node metastasis, ER, PR, Ki-67 and P53 expressions (P>0.05).Conclusion:HER-2 gene rs2517955 loci polymorphism is correlated with its protein expression. Further studies may be helpful to elucidate the mechanism of HER-2 protein expression in breast cancer.
ABSTRACT
Background and purpose: Adequate tissue ifxation, transparent dewaxing is an important step of hematoxylin eosin (HE) staining and lfuorescence in situ hybridization (FISH) in detection of breast cancerHER-2 gene. The purpose of this study was to make a comparison between poly hydroxyl acrylic acid which is an environmen-tally friendly ifxation liquid and 4% neutral buffered formaldehyde in tissue ifxation for HE staining and FISH to detect theHER-2 gene in the breast cancer tissue sections. The study aimed to evaluate the feasibility of replacing 4% buffered formaldehyde, a traditional ifxation liquid, with the poly hydroxyl acrylic acid, an environmentally friendly ifxation lfuid.Methods:This project was performed on tissue samples collected from 69 cases of breast cancer, 41 cases of breast ifbroadenoma, 40 cases of uterine leiomyoma, 25 cases of cervical tissue, 25 cases of placenta obtained from the outpatient and inpatient departments of Zhongshan Boai Hospital from Mar. 2011 to Jan. 2015, from each of which two samples were drawn and two blocks of each specimen were divided into two groups randomly. Then one group was ifxed with 4% neutral buffered formaldehyde and made into 200 sections by HE while the other group was ifxed with poly hydroxyl acrylic acid and made into another 200 sections. The slice level of the two groups was determined by the staining condition of the sections, and SPSS 19.0 was employed to compare the excellent and good rate of HE staining. Additional 69 sections were produced with two groups of breast invasive ductal carcinoma tissues, and SPSS 19.0 was used to detect the ampliifcation ofHER-2 gene by FISH.Results:First, the number of best-quality slices stained with HE ifxed separately by poly hydroxyl acrylic acid and 4% neutral buffered formaldehyde was 155 and 166, respectively. The number of excellent pieces was 41 and 33, respectively, while the number of mediocre pieces was 3 and 1 with bad pieces being 1 and 0, respectively. The excellent and good rates of HE staining were 98% and 99.5%, respectively. There was no significant difference between the two groups (χ2=1.33,P>0.05).Second, the positive rates of the tis-sue slices by FISH ifxed separately by poly hydroxyl acrylic acid and 4% neutral buffered were 26.09% and 23.19%, respectively. There was no signiifcant difference between the two groups (χ2=0.50,P>0.05).Conclusion:The results obtained with HE staining and FISH using poly hydroxyl acrylic acid as a ifxation liquid are not signiifcantly different from those using 10% neutral buffered formaldehyde. Therefore, poly hydroxyl acrylic acid meets the requirements of environmental protection, and thus has the potential to be promoted and widely used.
ABSTRACT
The study aimed to verify the prognostic utility, therapeutic application and clinical benefits of tumor substaging and HER2 status in papillary non-muscle invasive bladder cancer (NMIBC). Select NMIBC transurethral resection specimens from 141 patients were used to construct tissue microarrays for assessing the substaging, HER2 protein expression by immunohistochemistry (HER2-IHC) and gene amplification by dual-color silver in situ hybridization (HER2-SISH). Substages were identified by the differing depth of tumor invasion (pTa / pT1a / pT1b / pT1c). HER2 protein expression was semiquantitatively analyzed and grouped into negative (score 0, 1+) and positive (score 2+, 3+). Other clinicopathological variables were also investigated. For NMIBC, HER2-IHC and HER2-SISH showed positive results in 6/141 (4.3%) and 4/141 (2.8%) respectively, which correlated well with tumor substaging. In multivariate analysis, substaging, HER2-IHC, and HER2-SISH were found to be independent predictors of progression-free survival (P < 0.001, P < 0.001, P = 0.031). HER2-IHC was the sole independent predictor of recurrent free survival in NMIBC (P = 0.017). It is suggested that tumor substaging and HER2 status are independent predictive markers for tumor progression or recurrence, and thus could be included in diagnostic and therapeutic management for NMIBC.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Biomarkers, Tumor/metabolism , Carcinoma, Papillary/metabolism , Carcinoma, Transitional Cell/metabolism , Neoplasm Staging , Receptor, ErbB-2/metabolism , Reproducibility of Results , Sensitivity and Specificity , Urinary Bladder Neoplasms/metabolismABSTRACT
In recent years,with the development of tumor molecular biology technology,molecular targeted therapy has become a study hotspot,which plays a significant role on breast cancer treatment strategy.Among them,the human epidermal growth factor receptor-2 (Her-2) has been proven as an effective molecular target.So molecular targeted therapy of breast cancer become another important treatment except chemotherapy and endocrine therapy.
ABSTRACT
Oncogene activation and inactivation of tumor suppressor genes is an important molecular mechanism of tumor formation. HER-2 oncogene is associated with breast cancer invasion and metastasis and prognosis, HER-2 overexpressing breast cancer progresses rapidly and has poor prognosis. In recent years, the emergence of targeted therapeutic monoclonal antibody drug Herceptin which built its structure for the HER-2 has significantly inproved HER-2-positive advanced breast cancer.
ABSTRACT
PURPOSE: This study aimed to investigate the clinical significance of chromosome 17 centromere (CEP17) multiplication (increased copy number of CEP17) related to human epidermal growth factor receptor 2 (HER2) and topoisomerase II alpha (TOP2A) status in patients with invasive breast cancer. METHODS: We constructed tissue microarrays using 594 invasive breast cancer samples and performed single-color silver-enhanced in situ hybridization (SISH) assay for HER2, TOP2A, and CEP17 to assess for copy number aberrations. The association of CEP17 multiplication with patient survival was analyzed according to HER2 and TOP2A status. RESULTS: Among 567 informative cases, HER2 amplification was noted in 22.8%, TOP2A amplification in 8.3% and TOP2A deletion in 11.1%. CEP17 multiplication was identified in 33.2% and was significantly associated with worse overall survival (OS) (p=0.02) and disease-free survival (DFS) (p=0.02). CEP17 multiplication correlated with patient survival in patients with normal TOP2A or non-amplified HER2 status, but the prognostic significance was lost in those with altered TOP2A or amplified HER2. On multivariate analyses, CEP17 multiplication was an independent prognostic factor for poorer OS (p=0.02) and DFS (p=0.01) in patients with normal TOP2A and non-amplified HER2. CONCLUSION: CEP17 multiplication was identified as a promising prognostic marker in patients with invasive breast cancer exhibiting either non-amplified HER2 or normal TOP2A status.
Subject(s)
Humans , Antigens, Neoplasm , Breast , Breast Neoplasms , Centromere , Chromosomes, Human, Pair 17 , Coat Protein Complex I , Disease-Free Survival , DNA Topoisomerases, Type II , DNA-Binding Proteins , Genes, erbB-2 , In Situ Hybridization , Multivariate Analysis , Prognosis , ErbB Receptors , Receptor, ErbB-2ABSTRACT
PURPOSE: This study aimed to investigate the clinical significance of chromosome 17 centromere (CEP17) multiplication (increased copy number of CEP17) related to human epidermal growth factor receptor 2 (HER2) and topoisomerase II alpha (TOP2A) status in patients with invasive breast cancer. METHODS: We constructed tissue microarrays using 594 invasive breast cancer samples and performed single-color silver-enhanced in situ hybridization (SISH) assay for HER2, TOP2A, and CEP17 to assess for copy number aberrations. The association of CEP17 multiplication with patient survival was analyzed according to HER2 and TOP2A status. RESULTS: Among 567 informative cases, HER2 amplification was noted in 22.8%, TOP2A amplification in 8.3% and TOP2A deletion in 11.1%. CEP17 multiplication was identified in 33.2% and was significantly associated with worse overall survival (OS) (p=0.02) and disease-free survival (DFS) (p=0.02). CEP17 multiplication correlated with patient survival in patients with normal TOP2A or non-amplified HER2 status, but the prognostic significance was lost in those with altered TOP2A or amplified HER2. On multivariate analyses, CEP17 multiplication was an independent prognostic factor for poorer OS (p=0.02) and DFS (p=0.01) in patients with normal TOP2A and non-amplified HER2. CONCLUSION: CEP17 multiplication was identified as a promising prognostic marker in patients with invasive breast cancer exhibiting either non-amplified HER2 or normal TOP2A status.
Subject(s)
Humans , Antigens, Neoplasm , Breast , Breast Neoplasms , Centromere , Chromosomes, Human, Pair 17 , Coat Protein Complex I , Disease-Free Survival , DNA Topoisomerases, Type II , DNA-Binding Proteins , Genes, erbB-2 , In Situ Hybridization , Multivariate Analysis , Prognosis , ErbB Receptors , Receptor, ErbB-2ABSTRACT
PURPOSE: Amplification of the human epidermal growth factor receptor 2 (HER2) gene occurs in 18% to 20% of breast cancers, and it is recognized as a prognostic and predictive marker. We investigated the HER2 status in Korean breast cancer by immunohistochemistry (IHC) and silver-enhanced in situ hybridization (SISH), as the first step toward building a nationwide quality assurance program for HER2 testing. METHODS: A total of 1,198 breast carcinoma samples were collected from six institutions and IHC and SISH were performed using tissue microarrays in central laboratories. The results were compared to those of local laboratories. RESULTS: Available data were obtained from 959 samples. Central IHC results were negative, equivocal, and positive for 756 (78.8%; range among institutions, 76.8-81.8%), 37 (3.9%; 1.9-6.2%), and 166 (17.3%; 13.6-20%), respectively. SISH results were negative, equivocal, and positive for 756 (78.8%; 77.4-79.9%), 2 (0.2%; 0-0.7%), and 201 (21%; 20.1-22.2%), respectively. HER2 gene amplification was observed in 4.4%, 19%, and 73.9% of the negative, equivocal and positive groups stratified by local IHC results, respectively. When central SISH was considered to be the gold standard method for measuring HER2 status, the false-negative and false-positive rates of local IHC were 14.4% (29/201) and 7.1% (54/756). The concordance rate between central IHC and SISH was 98.4%. CONCLUSION: Central IHC and SISH markedly decreased the interlaboratory variability of HER2 status and the results of the two were highly concordant. The quality control program for HER2 testing must be focused on decreasing both the false negativity and positivity of IHC in local laboratories.
Subject(s)
Humans , Breast , Breast Neoplasms , Genes, erbB-2 , Immunohistochemistry , In Situ Hybridization , Quality Control , ErbB Receptors , Receptor, ErbB-2 , Resin CementsABSTRACT
0.05). Women with triple negative breast cancer experienced more lymph node metastases (71.9%︰58.5%,P=0.034),with the higher percentage of more than 10 lymph nodes metastases(26.0%)as compared with Her-2-overexpressing breast cancer (12.2%,P=0.034). A higher percentage of histological grade 3 was identified in triple-negative (67.7%)than in Her-2-overexpressing breast cancer(42.1%,P0.05). However,significantly poorer 5-year DFS was seen in patients with triple negative phenotype (61.85 months)than with Her-2-overexpressing phenotype (78.69 months,P=0.047). Conclusion Triple-negative breast cancers were more aggressive,and these women had poorer DFS comparing with Her-2-overexpressing ones.
ABSTRACT
Objective To explore the correlation of the ER and HER-2 expression status with the short-term effect of paclitaxel and epirubicin (TE) chemotherapy advanced breast cancer. Methods Past Immunohistochemical data of 42 advanced breast cancer patients after paclitaxel combined epirubicin treatment were analyzed retrospectively. Patients were divided into four sub-groups: ER +, HER-2-group; ER +, HER-2 + group; ER-, HER-2-group; ER-, HER-2 + group. All affecting patients with complete clinical and pathological data were observed for the factors short-term effect of TE chemotherapy and for chemotherapy adverse. Results The whole 42 patients completed at least two cycles of chemotherapy, and then got efficacy evaluation. Recent response rate of the patients who got TE chemotherapy was 23 cases (54.8%).RR with different metastatic sites (P=0.038) and the number of metastasis (P=0.036) were significantly different. The mainly adverse events of chemotherapy were alopecia for 36 cases (85.7%), myelosuppression for 29 cases (69.1%), Peripheral neuritis for 10 cases (23.9%). ER,HER-2 expression in the Different sub-groups and the RR showed linear distribution (P= 0.027).RR values (83.3%) in patients of ER-, HER-2 + group was significantly higher than that of the ER +, HER-2-group (25.6%) (P=0.045). Conclusion Advanced breast cancer patients with ER-, HER-2 + were more sensitive to TE chemotherapy.ER and HER-2 expression status was a predictor of efficacy of the chemotherapy. It may be helpful to consider ER and HER-2 expression status in choosing reasonable chemotherapy.
ABSTRACT
BACKGROUND: S Phase Kinase Associated Protein 2 (Skp2), an F-box protein necessary for DNA replication, has recently been demonstrated to be an oncogene. The purpose of this study was to examine the Skp2 expression and to investigate its association with expressions of estrogen receptor (ER), androgen receptor (AR) and HER-2, as well as clinicopathological variables including tumor recurrence. METHODS: The expressions of Skp2, ER and AR were examined by immunohistochemistry and HER-2 amplification by chromogenic in situ hybridization (CISH) in 117 cases of breast carcinoma. RESULTS: Skp2 was expressed in 26 patients (22.2%) and was significantly correlated with tumor type (p=0.031), tumor grade (p=0.017) and ER expression (p=0.038). Twenty four (20.5%) of 117 patients had a tumor recurrence, and 6 patients (5.1%) died of multifocal metastases. Tumor recurrence was significantly correlated with histological grade (p=0.041) and lymph node status (p<0.001). CONCLUSIONS: Although Skp2 expression was statistically insignificant in association with tumor recurrence, it might be useful as a biologic predictor in breast cancer. The simple and reliable immunohistochemical assay presented in this study can be a routine part of breast cancer evaluation and may influence patient management.
Subject(s)
Humans , Breast Neoplasms , Breast , DNA Replication , Estrogens , Immunohistochemistry , In Situ Hybridization , Lymph Nodes , Neoplasm Metastasis , Oncogenes , Receptors, Androgen , Recurrence , S Phase , S-Phase Kinase-Associated ProteinsABSTRACT
PURPOSE: The human epidermal growth factor receptor-2 (HER2) is overexpressed in breast cancer. The subset of patients with breast cancer demonstrating a HER2-positive status has aggressive tumors and a poor prognosis. Knowledge of the HER2 status is prerequisite when considering a patient's eligibility for anti-HER2 targeted therapy (Herceptin(R)). There are several assays available for determining the HER2 status. The aim of this study was to compare and evaluate the HER2 status in breast cancer by means of immunohistochemistry (IHC), FISH and real-time PCR. METHODS: DNA samples from fresh tumor tissues of 20 patients with breast cancer were analyzed with real-time PCR, using the LightCycler-HER2/neu PCR assay. A tissue microarray, containing 20 samples obtained from formalin- fixed, paraffin-embedded tissues, was used for IHC and FISH (PathyVysionTM). RESULTS: The frequencies of HER2 gene amplification for real-time PCR and FISH were 35 and 65% respectively, and the IHC frequency of overexpression was 70%. This study showed 75% concordance between IHC vs. FISH, 65% between IHC vs real-time PCR and 70% between FISH vs. real-time PCR. Considering real-time PCR as the gold standard, this study showed sensitivities and specificities of 100 and 46.2% for IHC, and of 100% and 53.8% for FISH. CONCLUSION: These results demonstrated marked discordance for the HER2 stati according to the various methods used. IHC, a familiar cost-effective test, will undoubtedly remain in routine clinical practice for HER2 screening but confirmatory HER2 testing using either FISH or real-time PCR is recommended for indeterminate cases. Real-time quantitative PCR for HER2 appears to be clinically useful due to its simplicity and ability to produce rapid results.
Subject(s)
Humans , Breast Neoplasms , Breast , DNA , Epidermal Growth Factor , Genes, erbB-2 , Immunohistochemistry , Mass Screening , Polymerase Chain Reaction , Prognosis , Real-Time Polymerase Chain ReactionABSTRACT
Objective To explore the relevance among HER-2 gene amplification,microvessel density(MVD),tumor size,lymph node metastasis and histological grading,as well as to discuss the significance of the levels of HER-2 gene amplification and MVD on the prognostic judgment of breast cancer.Method From 2001 to 2005,30 breast cancer specimens were collected from the Affiliated Hospital of Academy of Military Medical Sciences.Coloring in situ hybridization(CISH) was used to examine HER-2 gene amplification in paraffin-embedded tissue samples.Microvessels in tissue were labeled by CD34 antibody using IHC,and the MVD was then counted under optical microscope.Result HER-2 gene amplification was found in 11 of 30 cases(36.7%).MVD in breast cancer samples with HER-2 gene amplification was 67.91?24.36,significantly higher than those samples without HER-2 gene amplification(47.48?13.27,P