HER-2/neu Testing in Breast Carcinoma: A Combined Immunohistochemical and Fluorescence In Situ Hybridization Approach

Ridolfi, Ren L.; Jamehdor, Mehdi R; Arber, Janet M.

doi:10.1038/modpathol.3880154

Cited by 184 publications

(113 citation statements)

References 17 publications

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“…These discrepancies were mainly represented by tumors detected as 2ϩ by A0485. This observation is in agreement with the recent findings of Ridolfi (11) and Lebeau (16). When closely investigating the tumors stained 2ϩ by A0485, 6 of 8 (75%) cases with chromosome 17 polysomy lacked HER2 gene amplification.…”

Section: Discussionsupporting

confidence: 83%

“…It is relatively easy to perform and has rapid turnaround time, and relatively low cost (1,4). However, commercially available antibodies have demonstrated wide variation in sensitivity and specificity for FFPE tissue samples, and the effect of the tissue fixative and pretreatment have a substantial effect on HER2 IHC staining (1,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21), although antigen retrieval and immunodetection system currently used have improved sensitivity of antibodies. In addition, the lack of universal scoring system and interobserver differences in interpretation of HER2 IHC result are also important issues (1,15,17,18,22,23).…”

mentioning

confidence: 99%

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Determination of HER2 Gene Amplification by Chromogenic In Situ Hybridization (CISH) in Archival Breast Carcinoma

Zhao

Wu²,

et al. 2002

Modern Pathology

149

110

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Section: Discussionsupporting

confidence: 83%

mentioning

confidence: 99%

Determination of HER2 Gene Amplification by Chromogenic In Situ Hybridization (CISH) in Archival Breast Carcinoma

Zhao

Wu²,

et al. 2002

Modern Pathology

149

110

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“…According to the authors, greater than or equal to 2ϩ "correlated with at least 1ϩ staining using the controls and criteria provided in the HercepTest kit (1)." However, we should point out that using the criteria employed by the HercepTest kit (DAKO), scores of 0 (no staining or staining in less than 10% of cells) and 1ϩ (incomplete membranous staining more than 10% of cells) are considered negative, whereas scores of 2ϩ (mild to moderate complete membranous staining in more than 10% of cells) and 3ϩ (strong complete membranous staining in more than 10% of cells) are considered positive indicators of HER-2/neu oncogene overexpression (17). Furthermore, in breast cancer, those tumors with 2ϩ immunoexpression appear to be a heterogeneous group of tumors, with less than half showing true amplification of the HER-2/neu oncogene by FISH analysis (17).…”

Section: Discussionmentioning

confidence: 99%

“…However, we should point out that using the criteria employed by the HercepTest kit (DAKO), scores of 0 (no staining or staining in less than 10% of cells) and 1ϩ (incomplete membranous staining more than 10% of cells) are considered negative, whereas scores of 2ϩ (mild to moderate complete membranous staining in more than 10% of cells) and 3ϩ (strong complete membranous staining in more than 10% of cells) are considered positive indicators of HER-2/neu oncogene overexpression (17). Furthermore, in breast cancer, those tumors with 2ϩ immunoexpression appear to be a heterogeneous group of tumors, with less than half showing true amplification of the HER-2/neu oncogene by FISH analysis (17). Recently, among 22 pretreatment osteosarcoma samples, Zhou and colleagues (18) reported a correlation between "cytoplasmic staining" of HER-2/neu and increased risk of pulmonary metastasis.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathologic Analysis of HER-2/neu Immunoexpression among Various Histologic Subtypes and Grades of Osteosarcoma

et al. 2001

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Overexpression of the HER-2/neu oncogene appears to have prognostic significance in breast cancer. Recently, some have reported a relationship between increased immunohistochemical expression in osteosarcoma and poor clinical outcome. Despite limited data, a pilot trial of Herceptin, which targets the oncogene product, has been initiated for the therapy of some metastatic osteosarcomas (CCG-P9852). Archival formalin-fixed, paraffin-embedded tissue obtained from 41 patients diagnosed with osteosarcoma was examined immunohistochemically by 2 antibodies against the HER-2/neu oncogene product: CB-11 (monoclonal, 1/100) and Oncor (polyclonal, 1/200). All but one tumor (case of recurrent dedifferentiated parosteal osteosarcoma) represented primary tumor samples; when applicable, only prechemotherapy biopsies were analyzed. The study sample included the full spectrum of histologic subtypes and grades of osteosarcoma (25 conventional high grade; 3 telangiectatic; 1 small cell; 6 parosteal; 1 periosteal; and 5 lowgrade intramedullary). A case of metastatic breast cancer with known overexpression of the HER-2/neu oncogene served as the positive control. Complete membranous positivity, considered prognostically significant in breast cancer, was not seen in any of our osteosarcoma cases. At least focal cytoplasmic positivity was documented in 40 (98%) tumors using the CB11 antibody and in 34 (83%) using the Oncor antibody. The intensity of the cytoplasmic staining (0, 1-3؉) did not correlate with histologic subtype/grade, response to chemotherapy (<90% versus >90% necrosis), metastasis, or survival. Immunohistochemical overexpression of the HER-2/neu oncogene, defined as complete membranous positivity, is not present in our series of osteosarcomas. Cytoplasmic positivity is observed in most osteosarcomas, irrespective of histologic subtype/grade, and is not associated with response to preoperative chemotherapy or disease progression.

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“…Ayrıca cerrahi materyalin patoloji laboratuvarına gelişinden itibaren immünohistokimyasal çalışmanın sonuçları fiksasyon ve tüm doku takip sürecinden etkilendiği için laboratuvarlar arası standardizasyonun güç olduğu düşünülür. Aslında İHK sanılandan daha güvenilir bir yöntem olup, negatif ve pozitif olgu tespitinde farklı laboratuvarlar arası (14) veya diğer standart yöntemler ile korelasyonu yüksektir (15,16).…”

Section: Introductionunclassified

Comparison of immunohistochemistry and fluorescence in situ hybridization for the analysis of her2/neu and topoisomerase ii-alpha status in human breast cancer

Pala¹,

Zekioğlu²,

Özdemir³

et al. 2010

TJPATH

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Objective: The aim of the study is to evaluate HeR-2 gene amplification ratio in c-erbB-2 score 2 breast carcinoma cases which have been controversial for targeted terapy and determinate its correlation with pathologic prognostic factors. Material and Method:We analyzed 80 infiltrating breast carcinomas, which were immunohistochemically score 2 with silver in situ hybridization (SISH) assay to determine Her-2 gene amplification. Afterwards cases have been grouped as amplification positive (AP) and amplification negative (AN). These groups have been compared with each other to reveal their relationship with pathologic prognostic factors.Results: 30% of the cases showed HeR-2 gene amplification with SISH. Median age of patients in AP group was 50.3 (±11.4). Median age of AN group was 56.7 (±13.0). We found that tumors in AP group had much higher mitotic rate (p= 0.044). Mean metastatic lenf node number in AP group was 10, while it was only 1 in AN group. Lenfovascular invasion was the other striking parameter which showed statisticaly significant correlation with HeR-2 amplification. We didn't find any statisticaly significant correlation between HeR-2 amplification and tumor size, histologic grade, nuclear grade, diameter of the largest metastatic lenf node, steroid receptor expression and tumor necrosis. Conclusion:Tumors that show HeR-2 gene amplification have much higher mitotic rate, increased metastatic lenf node number and increased lenfovascular invasion rate. Unignorable part of controversial immunohistochemically c-erbB-2 score 2 cases show HeR-2 gene amplification and we need to confirm these cases with genetic tests. SISH is a cheap, easy and cantitative alternative.

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HER-2/neu Testing in Breast Carcinoma: A Combined Immunohistochemical and Fluorescence In Situ Hybridization Approach

Cited by 184 publications

References 17 publications

Determination of HER2 Gene Amplification by Chromogenic In Situ Hybridization (CISH) in Archival Breast Carcinoma

Determination of HER2 Gene Amplification by Chromogenic In Situ Hybridization (CISH) in Archival Breast Carcinoma

Clinicopathologic Analysis of HER-2/neu Immunoexpression among Various Histologic Subtypes and Grades of Osteosarcoma

Comparison of immunohistochemistry and fluorescence in situ hybridization for the analysis of her2/neu and topoisomerase ii-alpha status in human breast cancer

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