Expression of HER-2/neu in Breast

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HER-2/neu overexpression correlates with increased expression of VEGF in primary breast carcinoma

HER-2/neu overexpression correlates with increased expression of VEGF in primary breast carcinoma

An association between HER-2/neu overexpression and VEGF expression could strengthen the hypothesis based on preclinical evidence that increased VEGF expression may be a result of HER-2/neu overexpression and may contribute to the aggressive phenotype of HER-2/neu overexpressing breast cancer cells. This would provide a rationale for combined therapeutic approaches targeting both VEGF and HER-2/neu. The primary aim of the present study was to determine possible associations between expressions of HER-2/neu and VEGF in breast carcinoma. A secondary aim was to see
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Study on Carcinomas of Breast with Special Reference to Expression of Vascular Endothelial Growth Factor and Her 2/neu

Study on Carcinomas of Breast with Special Reference to Expression of Vascular Endothelial Growth Factor and Her 2/neu

The up-regulation of HER-2 is associated with increased expression of vascular endothelial growth factor at both the RNA and protein levels in breast carcinoma cells and exposure of HER- 2-positive cells to Trastuzumab significantly decreases VEGF expression. Src, a downstream adaptor protein of the HER-2 signalling pathway, has been found to be a switch for VEGF production showing that VEGF is a downstream target of the HER-2 signalling pathway. The combination treatment with HER- 2/neu and mimics of VEGF peptide together, produce additive effects. This explains that targeting the two different receptors, brings about greater anti- tumour and anti-angiogenic effects both in vitro and in vivo [18-20].
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Exposure to depleted uranium does not alter the co expression of HER 2/neu and p53 in breast cancer patients

Exposure to depleted uranium does not alter the co expression of HER 2/neu and p53 in breast cancer patients

Conclusion In conclusion, the positive expression of these biomar- kers is associated with biologically aggressive tumors and poor prognostic profile. Although the samples were taken from an area where the exposure to depleted ura- nium is a risk, the incidence of co-expression of both p53 and HER-2/neu markers does not differ from simi- lar cancer samples in areas that have not been exposed to depleted uranium, though, the greater immunoex- pression of Her-2/neu in breast cancer in this popula- tion with risk for DU exposure, compared with findings on other populations not at risk, requires further inves- tigation as it may reflect the possible role of DU in the induction or acceleration of network signaling between different Her-2 receptors. New lines of treatment which includes genetic modulation of the signaling pathway of both genes should be considered in patients’ medical follow up. Unfortunately for DU, knowledge of the exposure time, dose absorbed, route, length of exposure and its health consequences on the Iraqi population is still lacking. This is chiefly due to restricted access of scientists required to conduct such study and should form the basis for future investigations.
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Association between HER-2/neu over-expression and clinico-pathologic parameters of breast cancer in northern Malaysia

Association between HER-2/neu over-expression and clinico-pathologic parameters of breast cancer in northern Malaysia

As breast cancer management requires consideration of several tumour-related factors, their correlation with other prognostic factors is important for clinicians. It is agreed in general that tumour size, number of lymph nodes involved and tumor grade are still the most powerful predictors of prognosis. During the recent years over expression of HER-2/neu has provided another target for treatment of breast cancer using monoclonal antibodies.

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Concordance of HER 2/Neu over Expression with Steroid Receptor Status in Female Breast Cancers

Concordance of HER 2/Neu over Expression with Steroid Receptor Status in Female Breast Cancers

lifetime. Moreover, with increased public awareness, more breast carcinomas are detected early, before axillary lymph nodes contain metastases. Two thirds of the invasive carcinoma will present with negative axillary lymph nodes. Recurrent tumors will develop in about 20% to 30% of patients with node negative invasive breast carci- noma and they are at risk of dying of disease. Those 20% to 30% of women who will have recurrence should be considered for aggressive adjuvant therapies. The remaining 70% to 80% probably need no further therapy be- cause they appear to have been cured by surgery alone, this group need not be subjected to the inconvenient and toxic effect of aggressive adjuvant therapies. Pathologists can assess risk factors for development of recurrent tumors and provide valuable information to care for these patients. These risk factors include determination of lymph node status, tumor size, tumor type, histological grade, lymphatic vascular invasion, tumor proliferation rate and hormone receptor status [4].
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Cytoplasmic p21WAF1/CIP1 expression is correlated with HER 2/ neu in breast cancer and is an independent predictor of prognosis

Cytoplasmic p21WAF1/CIP1 expression is correlated with HER 2/ neu in breast cancer and is an independent predictor of prognosis

Further in vivo studies are required to establish the signifi- cance of phosphorylated Akt in relation to HER-2 and sub- cellular localisation of p21 WAF1/CIP1 , with future possibilities that immunodetection of phosphorylated p21 WAF1/CIP1 may imply activation of this pathway. Clinical relevance of HER-2-expressing tumours with cytoplasmic p21 WAF1/CIP1 is emphasised by the independent prognos- tic significance of both parameters. Prognostic signifi- cance of cytoplasmic p21 WAF1/CIP1 at 5 years retains its predictive potential for OS and RFS at 9 years. The com- bined evaluation of cytoplasmic p21 WAF1/CIP1 and HER-2 positively did not increase prognostic significance in this study, due to limited patient numbers in the respective subsets. As previously reported, nuclear p21 WAF1/CIP1 expression was generally low and provided no prognostic information [17,33,35]. Future studies will be required to address what are the best markers.
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HER 2 NEU and BMI 1 gene expression in Invasive Ductal Carcinoma Breast and Its correlation with hormone receptors and other known prognostic factors

HER 2 NEU and BMI 1 gene expression in Invasive Ductal Carcinoma Breast and Its correlation with hormone receptors and other known prognostic factors

METHOD OF DATA COLLECTION: Detailed history of the cases regarding age, sex, menstrual history, side of the breast, type of procedure, history of neo adjuvant therapy, details of gross characteristics such as tumor size, nodal status details were obtained for all the 238 mastectomy cases reported during the period from Surgical Pathology records. Freshly cut and Hematoxylin Eosin stained 4 µ thick sections of the paraffin tissue blocks of mastectomy specimens were reviewed and graded using the Nottingham modification of the Scarf Bloom Richardson Grading system (Annexure III) and they are further evaluated for the presence of necrosis, lymphocytic response and lymphovascular invasion by tumor. 20 cases of each grade from Invasive ductal carcinoma NOS subtype were randomly selected from the total cases and their representative formalin fixed paraffin embedded tissue samples were subjected to Immunohistochemistry for a panel of 4 markers and to real time reverse transcriptase polymerase chain reaction for gene analysis. The results were recorded with photographs.
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HER 2 therapy  HER 2/neu diagnostics in breast cancer

HER 2 therapy HER 2/neu diagnostics in breast cancer

PBC patients had an elevated serum HER-2/neu level. It is possible that PBC patients with elevated serum HER-2/neu levels have more extensive disease than understood. In 50 publications representing 5,044 patients with MBC, we found (on average) that 48.6% (range 23% to 80%) had elevated serum HER-2/neu levels. In more than 40% of the reports, it was found that 50% or more of the MBC patients had elevated serum HER-2/neu levels [16]. Several recent papers [18,51-53] reported that 50% to 60% of MBC patients had an elevated serum HER-2/neu. This difference may have several explanations, such as differing patient populations or wider use of the standardized FDA cleared serum HER-2/neu test. It also may be that some reports employ hormone receptor-positive patients only whereas others include mixed populations. These data are in sharp contrast to the many publications indicating that only 20% to 30% of patients with PBC have HER-2/neu over-expression by IHC or FISH amplification. It also raises the possibility that HER-2/neu status can change, by whatever mechanism, from PBC to the MBC setting.
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Expression of Her-2/neu in extrahepatic cholangiocarcinoma

Expression of Her-2/neu in extrahepatic cholangiocarcinoma

Immunohistochemistry The usage of EHBC-TMA in our study allowed the entire cohort, NNB and EHBC tissues, to be analyzed on one slide, and the benefits of using TMA are well documented. 11 A known Her-2/neu-positive breast carcinoma was used as a positive control. For negative control, the primary antibody was omitted during the incubation step. The EHBC-TMA was incubated for 16 min with a Her-2/neu rabbit monoclonal antibody (clone 4B5, using the Benchmark XT; Ventana Medical Systems) and detected by ultraview universal DAB detection kit (using the Benchmark XT; Ventana Medical Systems, Inc.). Antigen retrieval was performed using the Ventana Cell Conditioner #1 for 32 min. The Her-2/neu protein expression was evaluated using the modified ToGA trial scoring criteria established for gastric and gastroesophageal carcinomas 12–14 as follows: 1) no staining or no membranous staining of tumor cells was scored as “0”; 2) tumor cells with faint membrane staining irrespective of the percentage of tumor cells were scored as “1 + ”; 3) tumor cells with weak to moderate membrane staining irrespective of the percentage of tumor cells were scored as “2 + ”; and 4) tumor cells with strong complete, basolateral, or lateral membrane reactivity irrespective of the percentage of tumor cells were scored as “3 + ”. 14 We used the presence of complete, basolat- eral, or lateral membranous reactivity in ≥ 10% of cells as the cutoff for positivity, as required by the published guidelines. 14 The Her-2/neu IHC score was calculated by two independent pathologists (RS and DC) and a consensus score was reached for each specimen.
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Correlation of ER, PR and Her-2/Neu with Histological Variants of Breast Carcinoma.

Correlation of ER, PR and Her-2/Neu with Histological Variants of Breast Carcinoma.

Vikash Kumar et al 73 (2007) studied HER-2/neu oncogene overexpression which was much higher among Indian breast cancer patients 46.3% in comparison to 25-30% in Western literature. In the present study Estrogen, Progesterone receptor or both were positive in 51.6% cases and both receptors were negative in 48.4% cases (Tab.6). HER-2/neu overexpression was in 42.7% cases (Tab.7). Hence this study is comparable with the studies conducted in the Asian countries. There appears to be a minimal variation in receptor expression; technically this could be explained by differences in technique of evaluation and inter laboratory variations.
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Patterns of HER-2/neu Amplification and Overexpression in Primary and Metastatic Breast Cancer

Patterns of HER-2/neu Amplification and Overexpression in Primary and Metastatic Breast Cancer

The HER-2/neu (also known as ERBB2) proto-oncogene, which encodes a trans- membrane growth factor receptor with tyrosine kinase activity, has become an important subject for human cancer re- search during the last decade. The impact of HER-2 amplification and expression on prognosis (1–12) and on the response to cytotoxic (4,13–18) and hormonal (15,19–22) therapies in breast cancer patients have been studied intensively. Studies of HER-2 represent a paradigm of how genetic findings have led to the development of a gene-specific therapy: In September 1998, the U.S. Food and Drug Administration approved trastuzamab (Herceptin), a recombinant monoclonal antibody targeting Her-2, for the treat- ment of metastatic breast cancer. Al- though trastuzumab binds to the Her-2 receptor with high affinity, the mecha- nism of action by which it causes tumor reduction is not understood. Despite the theoretic benefits of such a targeted treat- ment, not all patients respond favorably to trastuzamab treatment in practice. Among the patients with HER-2-positive meta- static breast cancer that is resistant to con- ventional cytotoxic treatment, only about 25% benefit from trastuzamab given in combination with cisplatin (23). The ge- netic features that distinguish the HER-2- positive breast cancers that respond to trastuzamab from those that do not remain unclear. However, it is possible that the extent of HER-2 amplification and/or overexpression in the primary tumor dif- fers from that in the metastases. The HER-2 status of the primary tumor, which is removed from the patient, determines whether or not trastuzamab treatment is prescribed. But trastuzamab works by tar- geting the metastases that remain in the patient. If at least some of the multiple metastases of an HER-2-positive primary breast tumor did not express HER-2, trastuzamab treatment would most likely not affect the course of the disease. A comprehensive, large-scale study compar- ing HER-2 gene copy numbers and pro- tein expression in primary tumors and in multiple different metastases derived from them has not been performed. To gain insight into the patterns of HER-2
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HER-2/neu and E-cadherin Expression and Microsatellite Instability in Gastric Dysplasia

HER-2/neu and E-cadherin Expression and Microsatellite Instability in Gastric Dysplasia

Both cytoplasmic and membranous HER-2/ neu proteins were confirmed to be a 185-kDa whole molecule by immunoblotting. 21 Garcia et al. showed that cytosolic HER-2 level of gastric carcinoma cells was associated with an unfavorable outcome. 32 It has been suggested that because proteins are synthesized in the ribosomes, the antibody may detect cytoplasmic precursors of the final product. 33 As with breast cancer, it has been observed that only cases with membrane reactivity are linked to HER- 2 gene amplification and clinical response to Herceptin therapy. 34
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Triple-negative (ER, PgR, HER-2/neu) breast cancer in Indian women

Triple-negative (ER, PgR, HER-2/neu) breast cancer in Indian women

The score for proportion staining multiplied by the score for staining intensity is equal to the score. Score 0 indicates that endocrine treatments or tamoxifen will definitely not work and such patients should receive an alternative first-line treatment. Score 2–3 indicates a 20% chance of response to endocrine treatment. Score 4–6 indicates a 50% chance of response to endocrine treatment. Score 7–8 indicates a good (75%) chance of response to endocrine treatment. 0 score is negative, which denotes no staining seen or staining seen in less than 10% of tumor cells. Score 1 + is negative, which denotes that a faint/barely perceptible membrane staining is detected in more than 10% of tumor cells but that the cells are stained in only part of the membrane. Score 2 + shows a borderline or weakly positive result, which denotes that weak to moderate complete membrane staining is seen in more than 10% of tumor cells. Score 3 + is strongly positive, which denotes that strong complete membrane staining is seen in more than 30% of tumor cells. True HER-2/neu positivity is shown by crisp brown-colored membrane staining in at least 30% of the invasive tumor. Score 3 is two steps higher than HER-2/neu expression in surrounding benign breast parenchyma.
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Her-2/Neu, Estrogen and Progesterone Receptor Expression In WHO Grade I Meningiomas

Her-2/Neu, Estrogen and Progesterone Receptor Expression In WHO Grade I Meningiomas

in addition to their similar steroid hormone receptor profiles, suggest that new treatment methods used for breast cancer tumors may also be viable options for meningiomas. [8,9] However, the role of sex steroids and Her-2/neu expression in the pathogenesis, progression, and treatment of meningiomas awaits investigation.

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Tumor escape and progression of HER 2/neu negative breast cancer under immune pressure

Tumor escape and progression of HER 2/neu negative breast cancer under immune pressure

nuclear staining along with cytosolic staining for IFN-g Ra in their tumors. Discussion If HER-2/neu-specific IFN-g producing T cells are involved in HER-2/neu loss and tumor recurrence, we might be able to detect such immune responses in patients with HER-2/neu negative breast cancer, who might have had undetectable HER-2/neu positive pre- malignant tumors in the past, that had lost HER-2/neu expression and progressed to invasive carcinoma under the immune pressure. The fact that 55-75% of patients with premalignant DCIS overexpress HER-2/neu in their tumor lesions and 75% of breast cancers are HER-2/neu negative would suggest the progression of HER-2/neu positive DCIS to HER-2/neu negative breast cancer is only in the tumor clones that express IFN-g Ra. We have already shown that T cell-mediated tumor antigen loss was due to hypermethylation of the neu promoter and loss of neu both at mRNA and protein levels [3,5].
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A study on role of HER 2/NEU over expression in gastric carcinoma in south Indian population

A study on role of HER 2/NEU over expression in gastric carcinoma in south Indian population

indicate poor prognosis and poor response to chemotherapy in HER2/NEU over expressed cases of gastric cancer, but as on now, no study is clear in India. Trastuzumab is a monoclonal antibody which specifically targets HER2 protein by directly binding to extracellular domain of receptor and successfully used for breast cancer patients ,but not yet been tried in India for gastric cancer patients. This study may pave way for the introduction of trastuzumab in treating patients with advanced gastric malignancies and thereby enhance survival rates and improve the quality of life of those patients justifying the cost benefits.
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Prevalence of HER-2/ neu receptor amplification and its effects over prognosis of the patients with breast cancer

Prevalence of HER-2/ neu receptor amplification and its effects over prognosis of the patients with breast cancer

was associated with Comedo carcinoma variant. 3-5 Later in subsequent studies HER-2/neu protein expression associated with breast cancers has been confirmed., further evaluation of this receptor appear warranted to confirm whether this marker can be clinically useful in stratifying patients into low risk groups, which may be followed conservatively, and high risk groups that may require extensive post biopsy surgical procedures to prevent recurrence and to rule out invasive disease with an aggressive phenotype. 6-7 HER-2 /neu gene expression has generally not been specifically implicated in progression or prognosis assessment of lobular carcinoma of breast, but it is strongly associated with increased disease recurrence and a poor prognosis. 8 Over expression is also known to occur in ovarian, stomach, and aggressive forms of uterine cancer. 9 Multiple studies reported a significant co-relation of serum HER-2/neu protein levels with recurrence, metastasis or shortened survival. It also predicts the resistance of breast cancer to chemotherapy and absence of clinical response to hormonal therapy even when estrogen assays are positive. 10 Hence it is concluded that HER-2/neu amplification is an independent predictor of shorter disease with free survival in both node negative node and positive note patients. 11
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The impact of nottinghem prognostic index (NPI) on the occurrence of relapses in her 2 / NEU positive breast cancer

The impact of nottinghem prognostic index (NPI) on the occurrence of relapses in her 2 / NEU positive breast cancer

Taking into account all previously described parameters that are strongly correlated with the expression of HER-2 / neu, as it was expected, and this parameter reflects the importance of prediction of recurrent disease in HER-2 / neu positive breast cancer as it is described in our and in other studies (Ménard et al., 2001; Miller et al., 2004; Kollias et al., 1999). In our series, 30 out of 33 patients with HER-2 / neu positive breast cancers are in unfavorable prognostic group (90%). This result is similar to the results of Tovey (2009) that reported 68% and Chia (2008) with 73% in a series of patients that have a negative lymph-node status, up to 87% of the patients reported in the series of Sidoni and coworkers (Sidoni et al., 2004). The parameters that are incorporated in the postoperative histopathological classification which determine the stage of the disease, showed that they correlate with the expression of Her-2 / neu thus, the stage of the disease, is an important element in determining the course and outcome of the disease.
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HER-2/neu Expression in Resectable Gastric Cancer and its Relationship with Histopathologic Subtype, Grade, and Stage

HER-2/neu Expression in Resectable Gastric Cancer and its Relationship with Histopathologic Subtype, Grade, and Stage

HER-2/neu gene is found to be amplifiend in 10% to 30% of human breast, ovarian, gastric and other diverse cancers including lung adenocarcinoma, uterine cervix carcinoma and squamous cell carcinomas of the head and neck (3-6). Depending on the methodological aspects of the assays, scoring criteria and case selection, the prevalence of HER-2/neu expression shows wide variation in different studies on various tumors.

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Triplex formation inhibits HER 2/neu transcription in vitro

Triplex formation inhibits HER 2/neu transcription in vitro

Triplex-forming oligonucleotides (TFOs) have been shown to bind to target DNA sequences in several human gene promoters such as the c-myc oncogene, the epidermal growth factor receptor, and the dihydrofolate reductase genes. TFOs have been shown to inhibit transcription in vitro and gene expression in cell culture of the c-myc and other genes. The HER-2/neu oncogene, which is overexpressed in breast cancer and other human

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