Testing for HER2 Status

Hanna, Wedad

doi:10.1159/000055398

Cited by 51 publications

(41 citation statements)

References 34 publications

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“…Some studies have found significant interobserver variability between pathologists in grading the intensity of HER2 staining by IHC. 3,10,16,19,27 High concordance of results between FISH and IHC with strong (3ϩ) staining and negative (0 to 1ϩ) staining are generally seen. However, a marked discordance in the classification of results is seen between the two methods in cases with weak (2ϩ) HER2 staining by IHC.…”

Section: Discussionmentioning

confidence: 96%

“…29 A common algorithm for determining HER2 status uses initial evaluation with IHC, followed by confirmatory testing by FISH of 2ϩ positive cases. 8,14,15,27,28 The incidence of positive gene amplification by FISH in cases with 2ϩ staining by IHC ranges from 17 to 42%. 19,28 Of these FISH-positive/IHC 2ϩ cases, 63 to 74% showed borderline to low-level amplification (HER2/CEP17 ratios 2.0 to 5.0).…”

Section: Discussionmentioning

confidence: 99%

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Analysis of HER2 Gene Amplification Using an Automated Fluorescence in Situ Hybridization Signal Enumeration System

Stevens

Almanaseer

González

et al. 2007

The Journal of Molecular Diagnostics

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The HER2 gene, amplified in 10 to 35% of invasive human breast carcinomas, has prognostic and therapeutic implications. Fluorescent in situ hybridization is one method currently used for assessing HER2 status, but fluorescent in situ hybridization involves the time-consuming step of manual signal enumeration. To address this issue , Vysis has developed an automated signal enumeration system , Vysis AutoVysion. A multicenter , blinded study was conducted on 39 formalin-fixed , paraffin-embedded invasive breast carcinoma specimens , including 20 HER2 nonamplified and 19 HER2 amplified (weakly to highly amplified) , provided in duplicate to each study site for analysis. Calculation of the HER2/CEP17 ratio and the hands-on time of both manual and automated enumeration approaches were compared. Overall agreement of HER2 classification results (positive and negative) was 92.5% ( The HER2 gene (ERBB2) is located on chromosome 17 (q11.2-q12) and encodes a 185-kd transmembrane glycoprotein with intracellular tyrosine kinase activity, which is closely related to the epidermal growth factor receptor.1-6 Overexpression of the HER2 oncogene seems to stimulate growth and cellular motility and has been implicated in several malignancies. 4,6,7 Approximately 10 to 35% of invasive human breast carcinomas are associated with HER2 protein overexpression.2,6,8 HER2 overexpression is considered an unfavorable prognostic factor and is associated with better response rates to trastuzumab (Herceptin) therapy and anthracycline-based chemotherapy regimens. 9 Most breast carcinomas that overexpress HER2 are invasive ductal adenocarcinomas (95.5%) and are high-grade tumors [histopathological grades 2 (28%) or 3 (69%)]. Overexpression of HER2 is rare in invasive lobular carcinoma (0.8%) and other specialized types of breast carcinomas. 8,10 Studies have shown that the most common mechanism (90 to 96%) of HER2 overexpression is gene amplification. 2,9,11,12 Widely used approaches to assess HER2 status include immunohistochemistry (IHC) to determine protein expression and fluorescent in situ hybridization (FISH) to determine HER2 gene copy number. 4,11,[13][14][15] Reportedly, FISH has shown greater interlaboratory concordance and has been found to be a better predictor of response to trastuzumab (Herceptin) therapy, as compared with IHC.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Analysis of HER2 Gene Amplification Using an Automated Fluorescence in Situ Hybridization Signal Enumeration System

Stevens

Almanaseer

González

et al. 2007

The Journal of Molecular Diagnostics

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“…5,6 Response to some types of chemotherapy and hormonal therapy also appears to be dependent on HER2 status. [9][10][11][12][13][14] Results of this study show CISH to be a practical and reliable alternative to FISH for the assessment of HER2 gene amplification in breast cancer specimens. A very high level of concordance was seen between CISH and FISH in each of the tumor sample groups tested.…”

Section: Discussionmentioning

confidence: 99%

Chromogenic in-situ hybridization: a viable alternative to fluorescence in-situ hybridization in the HER2 testing algorithm

Hanna

Kwok

2006

Modern Pathology

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Assessment of human epidermal growth factor receptor-2 status is standard practice in women with breast cancer. Most laboratories use immunohistochemistry as a screening test, with equivocal results confirmed by fluorescence in-situ hybridization (FISH). Chromogenic in-situ hybridization (CISH) is a relatively new method for detection of gene amplification using a peroxidase reaction, which can be viewed using a standard light microscope. This study was undertaken to validate CISH as a method for assessing human epidermal growth factor receptor-2 gene amplification. The gene amplification status of human epidermal growth factor receptor-2 immunohistochemistry negative (0/1 þ , n ¼ 69; Group 1), immunohistochemistry positive (3 þ , n ¼ 50; Group 2) and equivocal tumor samples (2 þ , n ¼ 135; Group 3) was evaluated by FISH and CISH, and the concordance between FISH and CISH results calculated. In Group 1, 67/69 cases did not show amplification by CISH and 69/ 69 showed no amplification by FISH. Two cases were discordant; therefore, fluorescence/CISH concordance was 97%. In Group 2, 46/50 cases were amplified by FISH and 47/50 cases were amplified by CISH; three cases were not amplified by either method (immunohistochemistry false-positives). Only one case showed discordant FISH and CISH results, making the fluorescence/CISH concordance 98%. In Group 3, 89/135 cases were not amplified and 37/135 were amplified by both methods. Nine cases were discordant, giving a fluorescence/CISH concordance of 93%. The discordant cases were those with very low or borderline amplification with FISH. The high level of concordance between FISH and CISH seen in this study suggests that CISH may be a viable alternative to FISH for use in the human epidermal growth factor receptor-2 testing algorithm.

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“…In addition to signifying a more aggressive form of breast carcinoma, overexpression of this receptor appears to confer altered sensitivity to systemic adjuvant therapy. 28,[33][34][35][36][37] One large study showed no difference in HER-2/ neu status in a large group of white, African-American, and Hispanic women. 8 In another study, overexpression of HER-2/neu was observed with similar frequency in African-American and white women.…”

Section: 30mentioning

confidence: 99%

A comparison of five immunohistochemical biomarkers and HER‐2/neu gene amplification by fluorescence in situ hybridization in white and Korean patients with early‐onset breast carcinoma

Choi

Shin

Lee

et al. 2003

Cancer

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BACKGROUNDThe objective of this article was to compare five tumor markers between white women in the U.S. and native Korean women with early‐onset breast carcinoma.METHODSSixty Korean women who were diagnosed with breast carcinoma at age 45 years or younger and 60 white women with breast carcinoma who were matched by age were selected for this study. The median age of both groups was 37 years. Paraffin embedded blocks of the primary tumor were processed for immunohistochemical staining of estrogen receptor (ER), progesterone receptor (PR), p53, cyclin D1, and HER‐2/neu.RESULTSThe proportion of tumors that stained positive for ER, PR, p53, and cyclin D1 in the Korean women were 47.5%, 42.4%, 28.8%, and 40.9%, respectively; in the white women, the proportions were 43.9%, 52.6%, 21.1%, and 59.1%, respectively. The differences between the white patients and the Korean patients were not statistically significant with respect to any of those variables. A significant difference was found in the expression of HER‐2/neu. Specifically, positive HER‐2/neu status was observed in 47.5% of Korean women, compared with overexpression in only 15.8% of white women (P < 0.001). Fluorescence in situ hybridization analysis for HER‐2/neu gene amplification on all HER‐2/neu positive samples that scored 2 + and 3 + demonstrated a significant difference (P = 0.007) in gene amplification between the two populations. Differences in HER‐2/neu positivity were observed for the entire cohort as well as among the subsets of patients with negative and positive lymph node status. No association was found between immunoreactivity for the five markers and axillary lymph node metastasis.CONCLUSIONSThe findings of high positivity of HER‐2/neu expression and gene amplification in Korean women with early‐onset breast carcinoma may have potential implications for local and systemic management of breast carcinoma, especially anti‐HER‐2/neu therapy for patients with hormone receptor negativity. Further research will be needed to identify biologic and genetic factors and their effects on the survival between different racial groups. Cancer 2003. © 2003 American Cancer Society.DOI 10.1002/cncr.11703

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Testing for HER2 Status

Cited by 51 publications

References 34 publications

Analysis of HER2 Gene Amplification Using an Automated Fluorescence in Situ Hybridization Signal Enumeration System

Analysis of HER2 Gene Amplification Using an Automated Fluorescence in Situ Hybridization Signal Enumeration System

Chromogenic in-situ hybridization: a viable alternative to fluorescence in-situ hybridization in the HER2 testing algorithm

A comparison of five immunohistochemical biomarkers and HER‐2/neu gene amplification by fluorescence in situ hybridization in white and Korean patients with early‐onset breast carcinoma

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