HER2 Gene Overexpression Research Articles

Expresión y amplificación del gen HER2 en el cáncer gástrico avanzado

Overexpression/amplification of the HER2 gene in advanced gastric cancer is a predictor of response to adjuvant therapy with monoclonal antibodies. To determine the frequency of HER2 gene overexpression and amplification in advanced gastric cancer. One hundred nine advanced gastric cancer biopsy specimens, from 76 men and 33 women aged 67 ± 14 and 62 ± 12 years respectively, were selected. Three histological patterns (diffuse, intestinal and mixed) were recognized. Automated immunohistochemistry was performed with monoclonal c-erbB-2 (NCL-356) Novocastra. Fluorescent in situ hybridization (FISH) for HER2 was performed in positive cases. In 39% of cases, immunohistochemical staining was negative. It was 1+, 2+ and 3+ positive in 15, 36 and 11% of cases, respectively. It was positive in 16% and 3% of intestinal type and mixed carcinomas, respectively. It was negative in all diffuse carcinomas. FISH was performed in 39 (2 +) cases and in 11 (3 +) cases. The gene amplification was positive in two (2 +) and 11 (3 +) cases (11.9%). The overall concordance between immunohistochemical staining and in situ hybridization was 85%. In advanced gastric cancer, HER2 gene overexpression or amplification was observed in 11% and 12% of cases, respectively.

Assessment of HER-2 gene overexpression in Isfahan province breast cancer patients using Real Time RT-PCR and immunohistochemistry

PurposeOverexpression of proto-oncogene HER-2 is one of the main molecular markers of breast cancer involved in prognosis and diagnosis and also in trastuzumab therapy. Thus, a request for the evaluation of HER-2 status in breast cancer has been increasing. The aim of our study was assessment of HER-2 overexpression in malignant and benign breast cancer specimens by Real Time RT-PCR technique and comparison of its results with IHC outcomes. MethodsTwenty benign and sixty malignant breast cancers in addition to fifteen normal breast tissue specimens were analyzed by Real Time RT-PCR method. Fresh tissue samples were disrupted by mortar and pestle. A syringe and a needle were used for complete homogenization of the tissues. The RNA was then isolated from the samples and converted to cDNA. A standard curve was initially plotted using BioEasy SYBR Green I and then all 95 specimens were studied by Real Time RT-PCR using 2−ΔΔCt method. Results23.3% of 60 malignant specimens showed HER-2 overexpression, while all of the benign samples represented the normal expression level of HER-2 gene. The concordance rate between the results of Real Time RT-PCR and IHC was 86.6%. ConclusionReal Time RT-PCR method is an almost reliable technique and at least can be used as a complementary method for confirming IHC results. This is emanated from relatively high rate of concordance between outcomes of IHC test, as a routine method of detecting the HER-2 gene expression status, and Real Time RT-PCR technique.

Parallel Visualization of Multiple Protein Complexes in Individual Cells in Tumor Tissue

Cellular functions are regulated and executed by complex protein interaction networks. Accordingly, it is essential to understand the interplay between proteins in determining the activity status of signaling cascades. New methods are therefore required to provide information on different protein interaction events at the single cell level in heterogeneous cell populations such as in tissue sections. Here, we describe a multiplex proximity ligation assay for simultaneous visualization of multiple protein complexes in situ. The assay is an enhancement of the original proximity ligation assay, and it is based on using proximity probes labeled with unique tag sequences that can be used to read out which probes, from a pool of probes, have bound a certain protein complex. Using this approach, it is possible to gain information on the constituents of different protein complexes, the subcellular location of the complexes, and how the balance between different complex constituents can change between normal and malignant cells, for example. As a proof of concept, we used the assay to simultaneously visualize multiple protein complexes involving EGFR, HER2, and HER3 homo- and heterodimers on a single-cell level in breast cancer tissue sections. The ability to study several protein complex formations concurrently at single cell resolution could be of great potential for a systems understanding, paving the way for improved disease diagnostics and possibilities for drug development.

Detection of Subclinical Trastuzumab-Induced Cardiotoxicity in Patients with Breast Cancer

In recent decades, the treatment of cancer has shown great development in the fields of surgery, radiation therapy and the emergence of cytotoxic chemotherapy and targeted cancer therapies (including monoclonal antibodies, tyrosine-kinase inhibitors and angiogenesis inhibitors). Consequently, there has been an increase in survival of patients with cancer, making cardiovascular complications related to chemotherapy be more carefully taken into consideration by cardiologists and oncologists. The most frequent clinical manifestation of cardiotoxicity is symptomatic or asymptomatic ventricular dysfunction that can progress to heart failure1. Ventricular dysfunction can occur not only after conventional chemotherapy with anthracyclines, but with the new antitumor agents, such as trastuzumab. Several studies have shown that screening for cardiotoxicity by assessing the ejection fraction may be inadequate to detect subclinical disease2. It is known that the time of implementation of cardiovascular therapy is an important prognostic factor in heart function recovery and to prevent heart failure development3. Thus, several biomarkers have been studied in an attempt at early detection of cardiotoxicity, particularly troponin, BNP and microRNAs4,5. However, the optimal time of collection, or an ideal population to be submitted to this screening is yet to be determined. In addition, more sensitive methods for the assessment of cardiac structure and function, such as magnetic resonance imaging and strain echocardiography seem to detect the subclinical forms of the disease2. Some medications commonly used in the management of heart failure have shown a beneficial effect on chemotherapy-related cardiotoxicity. The use of angiotensin-converting enzyme inhibitors in patients with troponin increase during chemotherapy can be an effective tool to prevent left ventricular dysfunction and late cardiovascular events6. However, there are no large studies that evaluated the effect of these medications on anticancer therapy efficacy. In the treatment of cardiotoxicity associated with the use of chemotherapeutic agents, beta-blockers, enzyme inhibitors and angiotensin-converting enzyme inhibitors seem to be effective. However, early treatment of ventricular dysfunction is important, considering the correlation between the time of start of ventricular dysfunction treatment and cardiac function recovery1. The HER2 gene amplification and/or overexpression of its protein occurs in approximately 20% of breast cancers and is associated with a worse prognosis7. New chemotherapeutic agents, targeted at the HER2 receptor and its action pathway, have revolutionized the treatment of this type of cancer8. Trastuzumab, a humanized monoclonal antibody, was the first targeted therapy against the HER2 pathway and its use has changed the natural history of HER2+ breast cancer, resulting in improved survival similar to HER2- breast cancers. Thus, trastuzumab has become the key point in the treatment of HER2 + breast cancer. However, despite the outstanding benefits in survival related to anti-HER2 treatment, a significant increase in drug-related cardiac toxicity has been observed9, with several cardiac dysfunction events reported in clinical studies with the use of trastuzumab. Although cardiac toxicity induced by anti-HER2 therapy is not completely understood, preclinical studies have demonstrated an important role of HER2 signaling pathway in cardiac physiology, since both HER2 receptors and its ligands are expressed in cardiomyocytes. Despite the benefits offered by anti-HER therapy, there is justified concern about the potential adverse cardiac events and studies are needed to assess ways of early detection of this toxicity, as well as the best way of handling it, as the pathways of toxicity and therapeutics10 may be superimposed. It is believed that diastolic dysfunction may precede the onset of left ventricular systolic dysfunction11. In this issue, Dores et al12 studied 51 women with HER2 + breast cancer for five months to assess the occurrence of early cardiotoxicity. Although they found no symptomatic heart failure, the authors showed that as early as the third month of treatment, there were differences in diastolic parameters after the use of trastuzumab. The authors found a statistically significant difference in the E/e' ratio from the beginning to the third month of follow-up related to a reduction in myocardial velocity, as assessed by tissue Doppler. More than half of patients (57.9%) showed a decrease in ejection fraction, but only one had a decrease below 55%. With the development of cardio-oncology and the constant advent of new chemotherapeutic agents, surveillance studies and the search for early markers of cardiac abnormalities in cancer patients is of great importance for the adequate management of these patients. Editorial under the responsibility of Cardiosource in Portuguese. http://cientifico.cardiol.br/cardiosource2/default.asp

The current state of breast cancer classification

Breast cancer is a highly heterogeneous disease due to its diverse morphological features, the variable clinical outcome and the response to different therapeutic options. It is therefore necessary to devise a clinically meaningful classification of the disease, which has to be scientifically sound, clinically useful and widely reproducible. The established histopathological classification has a limited clinical utility, due to insufficient prognostic and predictive power. More recent classification schemes, based on the immunohistochemical characterization of breast cancer for the assessment of hormone receptor status, HER2 gene over-expression or amplification and the proliferative fraction or on gene expression profiles, correlate much better with the clinical outcome and may be used to inform the choice of the systemic therapy.

HER2/neu testing for anti-HER2-based therapies in patients with unresectable and/or metastatic gastric cancer

AimTo study the HER2 gene amplification or overexpression in patients with advanced gastric cancer (GC) and their association with patient characteristics and patient survival.Patients and methodsTumour tissue samples from 148...

Detecting overexpression level of HER2 gene in NSCLC by real-time quantitative PCR and the 2[-Delta Delta C(T)] method

背景与目的正确评价HER2基因表达的状况对于肿瘤的施治具有重要的指导意义。以往的评价大多基于免疫组织化学法, 但结果变异性大。本研究旨在探讨实时定量PCR 2-ΔΔCt法检测非小细胞肺癌(non-small cell lung cancer, NSCLC)HER2基因表达的可行性。方法采用实时定量PCR 2-ΔΔCt法同时检测212例肺癌组织和与其匹配的非肿瘤组织HER2基因的表达, 评价过表达水平。结果肺癌组织中HER2基因的表达水平高于非肿瘤组织(T=67, P < 0.05), HER2基因的过表达率为34.0%。结论实时定量PCR 2-ΔΔCt法用于检测NSCLC HER2基因的表达是可行的。

P5-13-20: TOP2A Amplification Have Associated with Response to Anthracycline-Based Preoperative Chemotherapy in Primary Breast Cancer.

Abstract Background: Recent studies have suggested that HER2 gene amplification or overexpression have association with sensitivity of anthracycline-based chemotherapy. Preclinical studies found that TOP2A amplification or deletion only could be detected in HER2 amplification or over-expressive cases. And TOP2A protein is the target of anthracycline. In fact, the value of HER2 for predicting response to anthracycline-based chemotherapy in breast cancer may be more likely related to the concomitant amplification of the TOP2A gene. In this study we studied the association between TOP2A gene amplification and response to anthracycline-based preoperative chemotherapy. Methods: 309 early and local advanced breast cancer cases were enrolled in our study. HER2 proteins were qualitatively analysed by IHC, and TOP2A gene alterations were quantified by real-time polymerase chain reaction (RT-PCR) in primary tumor core biopsies from all HER2 over expressive cases. The enrolled patients received an intense dose dense (IDD) (CE, Cyclophosphamide + Epirubicin) or conventionally (TE, Paclitaxel+Epirubicin) scheduled anthracycline- based preoperative chemotherapy. The tumor was evaluated every two cycles. Median time on study for 309 patients with follow-up was 38 months. Results: The pCR was 14.3%. HER2 overexpression was found in 80/309 (25.9%) breast cancer cases, of which 61/80 cases have been tested for TOP2A status. 19/80 cases have not been tested for TOP2A status because of lacking core biopsies tumor tissue after pathological diagnosis. HER2 overexpression was associated with a significantly higher pCR rate compared to HER2 lower expression (27.5% vs. 9.6%, P&amp;lt;0.001). Further analysis was carried on and found the significantly higher pCR rate in TOP2A co-amplified cases compared to TOP2A deleted or normal cases (56.3% vs. 13.8%, P=0.001). HER2 overexpression was associated with a significantly higher pathologic complete response (pCR) rate only when TOP2A was co-amplified (56.3% vs. 9.6%, P&amp;lt;0.001), but not when deleted or normal (13.8% vs. 9.6%, P=0.183), compared to HER2 lower expression tumors. The interaction between HER2 or TOP2A and anthracycline-based regiment was observed not only in IDD but conventionally scheduled preoperative chemotherapy. Discussion: Previous studies demonstrate that TOP2A gene amplification may define a subtype of HER2−positive breast cancer, This subtype of breast cancer may be highly sensitive to anthracycline-based chemotherapy, which may improve progression in HER2 and TOP2A co-amplification cases. Howerver, this viewpoint needs suppose from preoperative chemotherapy. Using RT-PCR to test TOP2A statue from 61 primary breast cancer tumor tissue, we demonstrate that TOP2A amplification breast cancer have highly sensitive to anthracycline-based preoperative chemotherapy. This finding suggests that TOP2A as a predictive marker in breast cancer should be included in future studies. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-13-20.

Human primary ductal carcinoma in situ (DCIS) subtype‐specific pathology is preserved in a mouse intraductal (MIND) xenograft model

Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer. The current recognition that DCIS lesions exhibit inter- and intra-lesion diversity suggests that the process of evolution to invasive breast cancer is more complex than previously recognized. Here we demonstrate the reproducible growth of primary DCIS cells derived from patient's surgical and biopsy samples by the mouse intraductal (MIND) model. MIND involves injection of cells into the NOD-SCID IL2Rgamma$^{{\rm{null}}}$ (NSG) mouse mammary ducts. Twelve (eight unique and four repeats) DCIS and two atypical hyperplasia specimens, heterogeneous with respect to biomarker expression and histology, were injected into 48 mouse mammary glands and analysed for successful xenotransplantation. Overall, 14/34 and 11/14 MIND xenotransplanted glands contained human DCIS and atypical hyperplastic cells, respectively, after 8 weeks, which formed single and multi-layered epithelium inside the ducts, and were heterogeneous with respect to expression of human cytokeratins, oestrogen receptor α (ER), and HER2. ER protein expression was recapitulated in MIND xenografts at ratios similar to the corresponding patient biopsies. In both patient biopsies and corresponding MIND xenografts, HER2 protein expression and nuclear HER2 gene overexpression were restricted to the DCIS lesions and were not found in the surrounding stroma or normal ducts. The xenografted DCIS lesions recapitulate the pathology and heterogeneity of human disease, thus providing a powerful tool for the characterization of the distinct cellular and molecular basis of inter- and intra-tumoural heterogeneity and the processes of DCIS to early invasive breast cancer progression.

Marked Response to Single Agent Trastuzumab in a Patient with Metastatic HER-2 Gene Amplified Rectal Cancer

Overexpression or HER-2 gene amplification occurs in approximately 25% of invasive breast cancers and predicts response to the targeting therapeutic antibody trastuzumab (). In this report, trastuzumab was used in the treatment of a patient with metastatic colorectal cancer harboring HER-2 gene amplification and overexpression. There was a marked radiographic response to the trastuzumab. If a larger series confirms the efficacy of trastuzumab use in patients with colorectal cancers with HER-2 gene amplification, trastuzumab could help improve the outlook for patients with this unusual colorectal cancer variant.

When Tumor Suppressor TGFβ Meets the HER2 (ERBB2) Oncogene

Despite its tumor suppressive role in normal mammary epithelial cells, TGFβ has been reported to promote the migration, invasion and survival in breast cancer cells overexpressing the HER2 (ERBB2; neu) oncogene, and to accelerate the metastasis of neu-induced mammary tumors in mice. A clearer understanding of the molecular mechanisms underlying the crosstalk between TGFβ and HER2 has started to emerge. In recent studies reviewed here, the synergistic effect of TGFβ and HER2 on tumor progression has been shown to likely be a combined result of two distinct features: (1) loss of TGFβ's tumor suppressive effect through functional alterations in the anti-mitogenic effect of Smad-mediated transcription, and (2) gain of pro-survival and pro-migratory function through HER2-dependent mechanisms. In HER2-overexpressing breast cancer, this crosstalk results in increased cancer cell proliferation, survival and invasion, accelerated metastasis in animal models, and resistance to chemotherapy and HER2-targeted therapy. Thus, the transformed cellular context imparted by constitutively active HER2 signaling, as a consequence of HER2 gene amplification or overexpression, aborts the tumor suppressive role of TGFβ and facilitated the oncogenic role of this pathway. In turn, TGFβ potentiates oncogenic HER2 signaling by inducing shedding of the ERBB ligands and clustering of HER2 with integrins. Here we discuss recent studies examining Smad-dependent and -independent mechanisms of crosstalk between TGFβ and HER2. Therefore, blockade of TGFβ:HER2 crosstalk may suppress breast cancer progression and metastasis, and enhance the efficiency of conventional therapies in patients with HER2-overexpressing breast cancer.

The Functional Crosstalk between HER2 Tyrosine Kinase and TGF-βSignaling in Breast Cancer Malignancy

Accumulating evidence indicates a functional crosstalk between the HER2 (ErbB2) tyrosine kinase and the TGF-β signaling mediated by its serine/threonine kinase receptors. In HER2-overexpressing breast cancer, this crosstalk results in increased cancer cell proliferation, survival and invasion, accelerated cancer progression and metastasis in animal models, and resistance to chemotherapy and HER2-targeted therapy. The transformed cellular context with constitutively active HER2 signaling, as a consequence of HER2 gene amplification or overexpression, converts TGF-β from a tumor suppressor to a malignancy-promoting factor. TGF-β, in turn, potentiates oncogenic HER2 signaling by inducing shedding of the ErbB ligands and clustering of HER2 with integrins. In addition, TGF-β is associated with resistance to trastuzumab, an anti-HER2 therapeutic antibody. Recent mechanistic studies indicate that TGF-β and HER2 cooperate through both Smad-dependent and independent mechanisms. Blockade of HER2:TGF-β crosstalk may significantly enhance the efficiency of conventional therapies in breast cancer patients with HER2 overexpression.

β-Catenin pathway activation in breast cancer is associated with triple-negative phenotype but not with CTNNB1 mutation

Aberrant β-catenin expression as determined by assessment of its subcellular localization constitutes a surrogate marker of Wnt signalling pathway activation and has been reported in a subset of breast cancers. The association of β-catenin/Wnt pathway activation with clinical outcome and the mechanisms leading to its activation in breast cancers still remain a matter of controversy. The aims of this study were to address the distribution of β-catenin expression in invasive breast cancers, the correlations between β-catenin expression and clinicopathological features and survival of breast cancer patients, and to determine whether aberrant β-catenin expression is driven by CTNNB1 (β-catenin encoding gene) activating mutations. Immunohistochemistry was performed on a tissue microarray containing 245 invasive breast carcinomas from uniformly treated patients, using two anti-β-catenin monoclonal antibodies. Selected samples were subjected to CTNNB1 exon 3 mutation analysis by direct gene sequencing. A good correlation between the two β-catenin antibodies was observed (Spearman's r >0.62, P<0.001). Respectively, 31 and 11% of the cases displayed lack/reduction of β-catenin membranous expression and nuclear accumulation. Complete lack of β-catenin expression was significantly associated with invasive lobular carcinoma histological type. Subgroup analysis of non-lobular cancers or non-lobular grade 3 carcinomas revealed that lack/reduction of β-catenin membranous expression and/or nuclear accumulation were significantly associated with oestrogen receptor negativity, absence of HER2 gene amplification and overexpression, lack/reduction of E-cadherin expression and tumours of triple-negative and basal-like phenotype. Univariate survival analysis revealed a significant association between β-catenin nuclear expression and shorter metastasis-free and overall survival in the whole cohort; however, β-catenin nuclear expression was not an independent predictor of outcome in multivariate analysis. No CTNNB1 mutations were identified in the 28 selected breast carcinomas analysed. In conclusion, β-catenin/Wnt pathway activation is preferentially found in triple-negative/basal-like breast carcinomas, is associated with poor clinical outcome and is unlikely to be driven by CTNNB1 mutations in breast cancer.

Bright-field In Situ Hybridization for HER2 Gene Amplification in Breast Cancer Using Tissue Microarrays

HER2 gene amplification or overexpression occurs in 15% to 25% of breast cancers and has implications for treatment and prognosis. The most commonly used methods for HER2 testing are fluorescence in situ hybridization (FISH) and immunohistochemistry. FISH is considered to be the reference standard and more accurately predicts response to trastuzumab, but is technically demanding, expensive, and requires specialized equipment. In situ hybridization is required to be eligible for adjuvant treatment with trastuzumab in Australia. Bright-field in situ hybridization is an alternative to FISH and uses a combination of in situ methodology and a peroxidase-mediated chromogenic substrate such as diaminobenzidine [chromogenic in situ hybridization (CISH)] or multimer technology coupled with enzyme metallography [silver-enhanced in situ hybridization (SISH)] to create a marker visible under bright-field microscopy. CISH was introduced into diagnostic testing in Australia in October 2006. SISH methodology is a more recent introduction into the testing repertoire. An evaluation of CISH and SISH performance to assess patient outcome were performed using tissue microarrays. Tissue microarrays were constructed in duplicate using material from 593 patients with invasive breast carcinoma and assessed using CISH and SISH. Gene amplification was assessed using the American Society of Clinical Oncology/College of American Pathologists guideline and Australian HER2 Advisory Board criteria (single probe: diploid, 1 to 2.5 copies/nucleus; polysomy >2.5 to 4 copies/nucleus; equivocal, >4 to 6 copies/nucleus; low-level amplification, >6 to 10 copies/nucleus and high-level amplification >10 copies/nucleus; dual probe HER2/CHR17 ratio: nonamplified <1.8, equivocal 1.8 to 2.2, amplified >2.2). Results were informative for 337 tissue cores comprising 230 patient samples. Concordance rates were 96% for HER2 single probe CISH and SISH and 95.5% for single probe CISH and dual probe HER2/CHR17 SISH. Both bright-field methods correlated with immunohistochemistry results and with breast cancer-specific survival. HER2 SISH testing combines the advantages of automation and bright-field microscopy to facilitate workflow within the laboratory, improves turnaround time, and correlates with patient outcome.

HER2 status testing by immunohistochemical and fFluorescence in situ hybridization in China

e22233 Background: HER2 gene overexpression is associated with aggressive breast cancer and poor clinical prognosis. Humanized anti-HER2 monoclonal antibody trastuzumab, which is targeted HER2 protein has showed to improve overall survival in patients with HER2-positive breast cancer in both the metastatic and adjuvant settings. There are some differences in HER2 positive rate among difference reports in China. This study tested HER2 status by immunohistochemistry(IHC) and fluorescence in situ hybridization (FISH) and compared HER2 testing at central and regional laboratories in China. Methods: Assessment of HER2 status was performed by FISH using the HercepTeast kit at central laboratory and by IHC using commercial available anti-HER2 probe in formalin-fixed and paraffin-embedded tissue section of 280 breast cancer samples. IHC HER2 testing was performed on 149 samples in the central laboratory. IHC HER2 testing was performed on 80 samples at both central laboratory and regional laboratory. Results: 280 samples were tested 373 times testing by IHC and FISH. The results were showed in table 1 . 80 samples was tested by IHC at central and regional laboratory and testing results of 36.4% samples were accordant (K=0.038). 94.1% IHC3+ at central laboratory were HER2 FISH positive and 83.3% IHC 3+ at regional laboratory were HER2 FISH positive. 86.7% IHC 2+ at central laboratory were HER2 FISH positive and 62.7% IHC 2+ at regional laboratory were HER2 FISH positive. 17 samples were observed HER2 FISH positive in the 27 IHC 0/1+ tested at regional laboratoty. So good correlation was obsearved between FISH HER2 status and IHC results from central laboratory but not from regional laboratory. Conclusions: This study emphasized the important of accurate HER2 testing. HER2 FISH test should be performed for the IHC 2+ samples. Even HER2 FISH test maybe performed for IHC 0/1 sample according to clinical characteristics in China in order to make the patients have targeted therapy chance. [Table: see text] No significant financial relationships to disclose.

HER2 status and breast cancer therapy: recent advances

The phenotype imparted by expression of the HER2 gene in breast cancer and progress made in modifying the disease's natural history through pharmacologically modulating its function has served as a paradigm for rationally targeted therapy and personalized medicine. About 20-25% of breast cancer cases are associated with HER2 gene amplification and overexpression, creating a distinct subtype of breast cancer that is associated with more aggressive behaviour, higher likelihood of overall and brain metastases, and differential responsiveness to certain hormonal and chemotherapeutic agents. Anti-HER2 monoclonal antibodies have led to significant improvements in survival for both advanced and early stage HER2+ breast cancer, while newer agents, including other antibodies and HER2 receptor tyrosine kinase inhibitors and signal transduction modulators, are also demonstrating clinical activity and represent further opportunities to improve curability and quality of life.

Histopathological features of invasion of breast invasive ductal carcinoma and safety of breast-conserving surgery

In order to investigate the relationship between the extent of tumor invasion and the tumor size, axillary lymph nodes metastasis, Her-2 gene overexpression, and histologic grading in breast invasive ductal carcinoma as well as the optimal extent of excision during the breast-serving surgery, the clinical data of 104 patients with breast invasive ductal carcinoma who had received modified radical mastectomy were analyzed. The correlation analysis on invasive extent, which was evaluated by serial sections at an interval of 0.5 cm from 4 different directions taking the focus as the centre, and the tumor size, axillary lymph nodes metastasis, Her-2 gene overexpression, and histologic grading was processed. There was a significant correlation between invasive extent and tumor size (r=0.766, P<0.01), and lymph nodes metastases (r=0.574, P<0.01), but there was no significant correlation between invasive extent and Her-2 expression (r=0.106, P>0.05), and histologic grading (r=0.228, P>0.05). The 100% negative rate of infiltration in patients without nipple discharge with tumor size <2, 2-3 and >3 cm was obtained at 1.5, 2.0 and 2.5 cm away from the tumor respectively. It is concluded that the performance of breast-serving surgery in patients with breast invasive ductal carcinoma should be evaluated by tumor size in combination with axillary lymph nodes involvement to decide the possibility of breast-serving and the secure excision extent.

Is overexpression of HER-2 a predictor of prognosis in colorectal cancer?

BackgroundThe development of novel chemotherapeutic agents in colorectal cancer has improved survival. Following initial response to chemotherapeutic strategies many patients develop refractory disease. This poses a significant challenge common to many cancer subtypes. Newer agents such as Bevacizumab have successfully targeted the tyrosine kinase receptor epidermal growth factor receptor in metastatic colorectal cancer. Human epidermal growth factor receptor-2 is another member of the tyrosine kinase receptor family which has been successfully targeted in breast cancer. This may play a role in colorectal cancer. We conducted a clinicopathological study to determine if overexpression of human epidermal growth factor receptor-2 is a predictor of outcome in a cohort of patients with colorectal cancer.MethodsClinicopathological data and paraffin-embedded specimens were collected on 132 consecutive patients who underwent colorectal resections over a 24-month period at Mayo General Hospital. Twenty-six contained non-malignant disease. Her-2/neu protein overexpression was detected using immunohistochemistry (IHC). The HER-2 4B5 Ventana monoclonal antibody was used. Fluorescent insitu hybridisation (FISH) was performed using INFORM HER-2/Neu Plus. Results were correlated with established clinical and pathological predictors of outcome including TNM stage. Statistical analysis was performed using SPSS version 11.5.Results114 were HER-2/Neu negative using IHC, 7 showed barely perceptible positivity (1+), 9 showed moderate staining (2+) and 2 were strongly positive (3+). There was no correlation with gender, age, grade, Dukes' stage, TNM stage, time to recurrence and 5-year survival (p > 0.05). FISH was applied to all 2+ and 3+ cases as well as some negative cases selected at random. Three were amplified (2 were 3+ and 1 was 2+). Similarly, HER-2 gene overexpression did not correlate with established prognostic indicators.ConclusionHER-2 protein is over expressed in 11% of colorectal cancer patients. The gene encoding HER-2 is amplified in 3% of cases. Overexpression of HER-2 is not a predictor of outcome. However, patients who over express HER-2 may respond to Herceptin therapy.

RELATION BETWEEN HER-2 GENE EXPRESSION AND GLEASON SCORE IN PATIENTS WITH PROSTATE CANCER

HER-2 is a proto-oncogene of the tyrosine kinase receptor family on chromosome 17. Overexpression of this gene affects the growth and prognosis of some tumors. This study was performed to evaluate the expression of the HER-2 gene in patients with prostate cancer and its relation with the Gleason score.Pathology specimens of all men with prostate cancer who had undergone radical prostatectomy without any supportive treatment were studied. The Gleason scores of the specimens and the expression of HER-2 gene were examined. The expression of HER-2 was scored between zero and 3+ in accordance with the HercepTest method. Patients with scores of 2+ and 3+ were considered to be positive for HER-2 overexpression.Of 150 cancerous prostate specimens evaluated, 20 (13.3%) were positive for HER-2 gene overexpression. A weakly positive HER-2 overexpression (2+) was seen in 15 of them (75%) and the remaining 5 (25%) were strongly positive. The Gleason score was not different between the HER-2-positive and HER-2-negative patients (P = .08). Fourteen out of 97 patients (14.4%) with a Gleason score less than 7 and 6 out of 53 (11.3%) with scores of 7 or greater were positive for HER-2 overexpression.The frequency of HER-2 gene overexpression is not very high in our patients with prostate cancer, and we failed to show any association of HER-2 expression and the Gleason score.

Comparison of HER2 Detection Methods Between Central and Regional Laboratories in Greece

Purpose HER2 gene amplification and overexpression is associated with aggressive breast cancer and poor prognosis. Accurate HER2 testing of patients with breast cancer before treatment is important to ensure that as many patients with HER2-positive breast cancer as possible receive the most appropriate treatment and that women with HER2-negative disease avoid a potentially toxic therapy. This study compares immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) HER2 testing at central and regional laboratories in Greece. Patients and Methods The HER2 status of 458 breast cancer samples was determined by IHC in central and regional laboratories using commercially available anti-HER2 antibodies. FISH analysis, scored as number of signals or a ratio, was subsequently performed by the central laboratory on most samples. Various statistical analyses were used to examine concordance between test center results. Results Immunohistochemistry HER2 testing was successfully performed on 445 samples in the central laboratory and 381 samples in regional laboratories, with good concordance between central and regional laboratories. After FISH analyses of a large proportion of these samples, good correlation was observed between FISH HER2 status and IHC results from the central laboratory but not from regional laboratories. These data suggest that HER2 status determined by IHC in a central laboratory is generally more accurate than that determined by a regional laboratory. Conclusion This study emphasizes the importance of accurate HER2 testing and the need to continually check the reproducibility and reliability of the test.