Neu In Breast Cancer Research Articles

Evaluation of Her-2/neu in Breast Cancer: Comparison of Immunohistochemistry and Polymerase Chain Reaction.

In breast cancer, Her-2/neu amplification/overexpression predicts a poor clinical outcome, and enhanced survival benefits have been reported with Her-2/neu targeted therapy. Currently, there are several methods for assessing the amplification/overexpression of Her-2/neu, each having advantages and disadvantages. The aim of this work was to establish a reproducible, sensitive and specific method of testing for Her-2/neu, which could be used in diagnostic pathology laboratories. We compared the immunohistochemistry (IHC) detection of Her-2/neu overexpression, with differential polymerase chain reaction (PCR) to assess the gene amplification of the Her-2/ neu, in 163 cases of invasive ductal carcinoma of the breast using paraffin-embedded tissue. In addition, assessment of the appropriate cut off points was established. The overexpression of the Her-2/neu was detected in 39 (23.9%) cases, and its amplification in 37 (22.7%) cases. The methods were positive in 21.5% of cases and negative in 74.8%. There was a 96.3% concordance between the two methods. The sensitivity and specificity of IHC, compared with PCR, were 94.6 and 96.8%, respectively. We conclude that the automation of PCR-based Her-2/neu testing approaches is expected to play an increasing role in the future of Her-2/neu testing. Also, we have demonstrated that IHC is a sensitive and specific method for assessing Her-2/neu stati in breast cancer, compared to PCR. The current study indicates that moderate, or strong, complete membrane staining in> or =10% of tumor cells provides an appropriate cut off point compared with PCR.

HER-2/neu in Breast Cancer: Is Consensus Reached in Standard Testing?

HER-2/neu in Breast Cancer: Is Consensus Reached in Standard Testing?

HER-2/Neu signaling and therapeutic approaches in breast cancer

Amplification or overexpression of HER-2/neu occurs in 30% of human breast and ovarian cancers and is associated with a poor clinical outcome, including short survival and time to relapse. Recent advances in our understanding of HER-2/neu signaling pathways have significantly increased our understanding of the tumorigenesis of breast cancer and provided new targets for treating breast and ovarian tumors that overexpress HER-2/neu. In this review, we focus on the new signaling pathways mediated by HER-2/neu in breast cancer and discuss our understanding of these pathways, as they seem to be particularly important in mediating cell survival and growth under a wide variety of circumstances in breast cancer.

HER-2/neu in Breast Cancer: Interobserver Variability and Performance of Immunohistochemistry with 4 Antibodies Compared with Fluorescent In Situ Hybridization

The immunohistochemistry (IHC) performance of 4 anti-HER-2/neu antibodies was compared with fluorescent in situ hybridization (FISH) analysis of HER-2/neu gene expression in breast cancer patients considered for Herceptin (Trastuzumab) therapy. Interobserver variability in IHC interpretation was measured. Formalin-fixed tissue was received from 24 provincial hospital laboratories. The following anti-Her-2 antibodies were used: DAKO A0485 (polyclonal), Novacastra CB11 (monoclonal), Zymed TAB250 (monoclonal), and DAKO HercepTest (polyclonal). Additional sections were analyzed by FISH (Vysis). Three pathologists blinded to FISH results independently interpreted invasive tumor cell membranous staining on a scale of 0 to +3. The HER-2/neu gene was considered amplified when the FISH signal ratio of HER-2/CEP-17 was ≥2.0. Blocks from all hospitals and of all ages were suitable for IHC and FISH analysis. No interlaboratory analysis variability was noted. The interobserver agreement (kappa) for stain intensity for each antibody was good for 0 and +3 but poor for +1 and +2. Reasonable concordance between IHC and FISH was found with three of the four antibodies. TAB250 was the most sensitive antibody. For the three pathologists, the IHC sensitivities and specificities compared with FISH using 0/+1 as negative and +2/+3 as positive were as follows: A0485, 63–84/95–98; CB11, 63–66/97–98; TAB-250, 82–100/94–95; HercepTest, 59–77/91–93. The positive and negative predictive values varied by stain intensity. Stain scores of 0 and +3 were highly predictive of gene status. Stain scores of +1 and +2 were not sufficiently predictive to classify cases as amplified versus nonamplified. IHC is a reasonable first test to assess HER-2/neu status in patients with breast cancer. For most cases, DAKO A0485, TAB250, and HercepTest adequately predicted gene status. In cases with stain intensity of +1 or +2, the interobserver agreement is poor, and the predictive value is unsatisfactory for clinical use. Additional testing, preferably with FISH, is recommended.

Her-2/neu and breast cancer.

Breast cancer is the most common malignancy in women in the United States in the year 2000. The proto-oncogene Her-2/neu (c-erb-B2) has become an increasingly important prognostic and predictive factor in breast cancer. Overexpression/amplification of the Her-2/neu has been associated with a worse outcome in patients with breast cancer. Herceptin, a "humanized" murine monoclonal antibody directed against the extracellular domain of the Her-2/neu protein, is being used to treat breast cancer that overexpresses Her-2/neu. The status of Her-2/neu in the tumor has become a critical factor in the management strategy of a breast cancer patient. The objective of this article is to provide a comprehensive review of all aspects of Her-2/neu in breast cancer, including biology, prognostic and predictive value, targeted Herceptin therapy, and the laboratory testing of Her-2/neu.

Correlation of p27 protein expression with HER-2/neu expression in breast cancer.

Strong expression of human epidermal growth factor receptor 2 (HER-2)/neu in breast cancer has been associated with poor prognosis. Reduced expression of p27(Kip1), a cyclin-dependent kinase inhibitor, correlates with poor clinical outcome in breast cancer. In this study, we provide a correlation between these two important prognostic markers in patients with breast cancer. Breast tumor screening using immunohistochemistry indicated that downregulation of p27 correlated with HER-2/neu overexpression in studying 11 normal breast tissues and 51 primary breast carcinomas. We found HER-2/neu protein overexpression in 20 (41%) of 49 breast cancers and low p27 protein expression in 47 (92%) of 51 breast cancers. All 20 (100%) of the tumors that overexpressed HER-2/neu had low levels of p27 protein product; this correlation was statistically significant (P = 0.035). Decreasing p27 expression correlated with increasing HER-2/neu activity. Our results suggest that one function of the HER-2/neu product is to downregulate p27 expression in breast cancer. This study may be significant in selecting patients for HER-2/neu antibody therapy in the future. Mol. Carcinog. 30:169--175, 2001.

Marked Intratumoral Heterogeneity of the Proto-Oncogene Her-2/neu Determined by Three Different Detection Systems.

It is customary to submit only one portion of a breast cancer to determine if there is amplification or overexpression of the proto-oncogene HER-2/neu. In routine studies of the expression of neu in breast cancer, however, we noted discrepancies in intratumoral positivity. To investigate this phenomenon further, multiple tumor specimens (129 samples) from 41 women with breast cancer were examined. Forty cases were analyzed for neu amplification by slot blot assay and 18 with fluorescent in situ hybridization. Neu overexpression was determined using four different specific antibodies. In more than 50% of cases there were discrepancies in results between the tissue blocks examined. This was evident in both inter- and intra-assay comparisons. It is concluded that intratumoral heterogeneity of neu amplification/overexpression in breast cancer exists to a far greater degree than previously recognized and could be a responsible factor for conflicting published data regarding neu's prognostic significance. Examination of only one tumor sample may not give a true indication of either amplification or overexpression of this oncogene.