Assessment of protein expression and gene status of human epidermal growth factor receptor (HER ) family molecules in ameloblastomas
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To evaluate roles of human epidermal growth factor receptor (HER) family molecules in ameloblastomas, protein expression and gene status were analyzed in odontogenic tissues.Sixty five ameloblastomas, 10 dental follicles, and 11 dentigerous cysts were immunohistochemically examined with antibodies against epidermal growth factor receptor (EGFR) and HER2, HER3, and HER4. Amplification of EGFR and HER2 was evaluated by chromogenic in situ hybridization (CISH). In 18 ameloblastomas, EGFR exons 19 and 21 were analyzed by direct DNA sequencing.Immunohistochemical reactivity for EGFR and HER2, HER3, and HER4 was detected in odontogenic epithelium. Expression of EGFR and HER4 was remarkable in these odontogenic tissues, as compared with that of HER2 and HER3. The level of HER2 immunoreactivity was significantly lower in ameloblastomas than in dental follicles and dentigerous cysts. Follicular ameloblastomas showed significantly higher expression of HER2 and HER4 than plexiform ameloblastomas. Reactivity for EGFR and HER3 was slightly stronger in recurrent ameloblastomas than in primary ameloblastomas. CISH did not reveal obvious amplification of EGFR or HER2 in ameloblastomas; however, EGFR and HER2 gene signals were significantly higher in follicular ameloblastomas than in plexiform ameloblastomas. Direct DNA sequencing of EGFR did not show any gene alteration in ameloblastomas.Expression of HER family molecules, especially EGFR and HER4, in odontogenic tissues suggests that growth signals mediated by these receptor molecules contribute to cell proliferation, survival, and differentiation in both normal and neoplastic odontogenic epithelial tissues. Some of these molecules might be useful for predicting outcomes in patients with ameloblastomas.Keywords:
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Objective: To determine the HER-2/neu status by chromogenic in situ hybridization (CISH) on tissue specimens with a borderline (2+) immunohistochemistry (IHC) score in carcinoma breast by a descriptive, cross-sectional study in the Histopathology Department, Armed Forces Institute of Pathology (AFIP), Rawalpindi from Jun 2008 to Dec 2009. Methods: Tissue block specimens from 50 consecutive patients having HER-2/neu score of borderline (2+) on IHC assay were tested for HER-2/neu gene amplification by CISH. Mean and standard deviation were calculated for quantitative variables like age and HER-2/neu gene copy signal/clusters by using SPSS version 14. Frequencies and percentages were also calculated for qualitative variables like type of carcinoma and results of HER-2/neu by CISH (amplified/nonamplified). Results: HER-2/neu gene amplification by CISH was found in 10 (20%) out of 50 patients with borderline (2+) IHC score. All CISH amplified cases belonged to invasive ductal carcinoma type. No significant correlation was noted between type of carcinoma and HER-2/neu gene amplification. Conclusion: Chromogenic in situ hybridization (CISH) is a practical, cost-effective and reliable method for analysis of HER-2/neu borderline (2+) cases which may be candidates for Herceptin therapy.
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Chromogenic
Breast carcinoma
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Objective To evaluate the sensitivity and specificity of chromogenic in-situ hybridization(CISH)in detecting HER2 gene amplification in breast carcinomas.Methods HER2 oncogene amplification and its protein expression in 165 cases of breast carcinoma were investigated by immunohistochemistry(IHC)and CISH.Results(1)CISH did not detect HER2 gene amplification in 107 cases of IHC negative tumors and 24 cases of IHC 1+tumors.(2)CISH identified high copy numbers of HER2 gene amplification in 21/22(95.5%)cases with IHC 3+.(3)In 12 HIC 2+cases,CISH identified 3 cases of high copy number amplification,6 cases of low copy number amplification and 3 cases without amplification.Conclusions HER2 gene amplification detection by CISH is highly sensitive and has a high concordance with IHC detection of the protein expression.It is concluded that CISH is a tool to evaluate HER2 gene status in breast cancer and can be an implement in conventional pathology laboratories.
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Objective To explore the effect of CISH on detecting gene amplification of HER-2 in breast cancer and to compare the results with those obtained by immunohistochemistry(IHC).Methods CISH for HER-2 gene expression was performed using SPOT-Light HER2 CISHTM on the archival paraffin-embedded sections of breast cancer tissues from 40cases with immunohistochemical staining scores of(+++),(++),(+).Results Of the 15 cases with score(+++) by IHC,14 cases showed HER-2 gene amplification by CISH,1 case CISH-negative.11 of the 16 cases with score (++) showed HER-2 gene amplification,the remaining 5 cases were CISH-negative.9 cases with score(+) were CISH-negative.Certain difference to the examination of HER-2 was found in the two kinds of method(P0.05).Conclusion Immunohistochemistry(IHC) is the first choice in primary screening for HER-2 expression status.Because of the obvious discrepancies between protein expression and gene amplification,patients with score(+～+++) by IHC should undergo CISH testing.
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Purpose To explore the application for clinical assessment of HER2 gene expression status by chromogenic in situ hybridization (CISH) and to compare the results with those obtained by immunohistochemistry(IHC). Methods CISH for HER2 gene expression status was performed using SPOT-Light HER2 CISHTM on the archival paraffin-embedded sections of breast cancer tissues from 40 cases with immunohistochemical staining scores of (+++),(++),(+) and (-). Results Of the 8 cases with score (+++) by IHC,7 cases showed HER2 gene amplification by CISH,1 case CISH-negative. Five of the 13 cases with score (++) showed HER2 gene amplification,the remaining 8 cases were CISH-negative. Two of 10 cases with score (+) showed HER2 gene amplification,the remaining 8 cases were CISH-negative. All the patients with scores negative (n=9) failed to show amplification. Certain difference to the examination of HER-2/neu status (kappa=0.458,P=0.003) was found in the kinds of method. Conclusion Immunohistochemistry(IHC) is the first choice in primary screening for HER2 expression status. Because of the obvious discrepancies between protein expression and gene amplification,patients with score (+++～+) by IHC should undergo CISH testing.
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In this study, we test the reliability of chromogenic in situ hybridization (CISH) for the detection of epidermal growth factor receptor (EGFR) gene amplification in glioblastoma. Earlier reports have described EGFR CISH in glioblastoma multiforme, but a comparison of CISH with a "gold standard" testing method, such as fluorescence in situ hybridization (FISH), has not been described. Therapies targeting the EGFR-signaling pathway might increase the importance of assessment of EGFR-amplification status. CISH is a potential alternative to FISH as a testing method. To test its reliability, EGFR-amplification status by CISH was assessed in 89 cases of glioblastoma and compared with FISH results, and correlated with the protein expression using immunohistochemistry (IHC) for EGFR. FISH was scored as being EGFR-amplified in 47/89 tumors, CISH as being amplified in 43/89 tumors. The CISH and FISH results were in agreement in 83/89 cases (93%). Four glioblastomas were scored as being amplified by FISH, but not by CISH; whereas amplification was detected in 2 tumors by CISH that were not amplified using FISH. Forty-eight of the 89 cases were positive for EGFR expression by IHC. EGFR amplification was highly correlated with protein expression by IHC, as 40/48 (83%) EGFR IHC-positive cases were found to be EGFR-amplified. The high concordance of CISH and FISH for the assessment of EGFR gene-amplification status indicates that CISH is a viable alternative to FISH for the detection of EGFR gene amplification in glioblastoma. Detectable EGFR expression by IHC can occur in the absence of gene amplification, but is uncommon.
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To evaluate the sensitivity and specificity of chromogenic in-situ hybridization (CISH) in detecting HER2 gene amplification in breast carcinomas.HER2 oncogene amplification and its protein expression in 165 cases of breast carcinoma were investigated by immunohistochemistry (IHC) and CISH.(1) CISH did not detect HER2 gene amplification in 107 cases of IHC negative tumors and 24 cases of IHC 1+ tumors. (2) CISH identified high copy numbers of HER2 gene amplification in 21/22 (95.5%) cases with IHC 3+. (3) In 12 HIC 2+ cases, CISH identified 3 cases of high copy number amplification, 6 cases of low copy number amplification and 3 cases without amplification.HER2 gene amplification detection by CISH is highly sensitive and has a high concordance with IHC detection of the protein expression. It is concluded that CISH is a tool to evaluate HER2 gene status in breast cancer and can be an implement in conventional pathology laboratories.
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Breast carcinoma
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The evaluation of HER2 status in invasive breast carcinoma can be performed by multiple methods. We assessed the feasibility of performing 2 of these, chromogenic in situ hybridization (CISH) and immunohistochemical staining, on single tissue sections of breast carcinoma. During assay development, sequential performance of immunohistochemical staining after CISH resulted in weaker HER2 expression than that obtained when immunohistochemical staining was performed alone; this was ameliorated by increased antibody incubation time. Performance of both techniques in a combined/hybrid protocol resulted in HER2 protein expression and gene signals identical to those produced by the individual techniques performed alone. Prospective validation of these dual staining protocols in 31 cases of breast carcinoma resulted in 100% concordance with results of CISH when performed alone, but was still associated with a reduced immunohistochemical signal in some cases. Although further testing is needed, we conclude that performance of both immunohistochemical staining and CISH on a single section is possible and could allow for direct "cell-by-cell" comparison of HER2 signals and potentially offer a more economical and real-time method for ongoing validation of HER2 testing.
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Immunohistochemical (IHC) testing for HER2/neu is becoming the standard of care for guiding the adjuvant treatment of gastric carcinoma with trastuzumab. Up to now, gastric cancer has been considered the most commonly diagnosed tumors leading to death. In this study, we evaluate the detection of HER2 expression by IHC in Tunisian patients with gastric cancer according to the international consensus. A total of 84 tumor specimens was assessed for HER2 expression by immunohistochemistry (IHC) using the antibodies HercepTest™. Doubtful IHC results (IHC 2+) were resolved by HER2 Chromogenic in situ hybridization (CISH). Thus, 10.5% of samples were HER2-positive (3+), 8.3% having a negative score IHC, Her2-Neu (+1) and 3.6% to be a dubious immunostaining Her2-Neu (2+).
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HER2/neu
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Her-2/neu testing is used as a marker for Herceptin therapy. The aim was to investigate new dual-colour chromogenic in situ hybridization (CISH), in a large number of breast carcinomas (n = 205) with DNA-specific dual-colour probes (ZytoVision, Bremerhaven, Germany) and to compare the results with immunohistochemistry (n = 205) and fluorescence in situ hybridization (FISH) (n = 129).Paraffin-embedded tissue of 205 patients was used. After immunohistochemistry with a focus on immunohistochemically uncertain cases, Her-2/neu amplification using dual-colour CISH (ZytoVision) was analysed. Validation by FISH was performed. The results were: immunohistochemistry, 27.8% with strong expression, 53.7% with uncertain overexpression and 18.5% with no expression; FISH, 25.6% amplified and 74.4% negative; CISH, 35.6% amplified, 62.9% negative and 1.5% not evaluable. Comparison of immunohistochemistry with CISH: CISH negative in 100% with immunohistochemistry 0/1+, amplified in 82.5% with immunohistochemistry 3+; 5.9% contradictory results: 4.4% immunohistochemistry 3+ and negative by CISH, 1.5% negative in immunohistochemistry but amplified by CISH; FISH (129 cases), 8.5% contradictory results to immunohistochemistry, 6.2% immunohistochemistry 3+ and negative by FISH, 2.3% negative by immunohistochemistry and amplified by FISH; comparison of CISH and FISH, 94.6% same results, 3.9% different ones, 1.6% CISH not analysable.CISH, using dual-colour probes (ZytoVision) is as good as FISH for Her-2/neu analysis. The few discrepant results are likely to be caused by polysomy or tumour heterogeneity.
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