Chromogenic In Situ Hybridization Is a Reliable Method for Detecting HER2 Gene Status in Breast Cancer A Multicenter Study Using Conventional Scoring Criteria and the New ASCO/CAP Recommendations

Department of Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
American Journal of Clinical Pathology (Impact Factor: 2.51). 05/2009; 131(4):490-7. DOI: 10.1309/AJCPI00TVGIGYXAA
Source: PubMed


Chromogenic in situ hybridization (CISH) has shown the potential to replace fluorescence in situ hybridization (FISH) to determine HER2 gene status. To validate the reliability of CISH, we used 226 consecutive breast carcinomas from 2 institutions and tested CISH and FISH on the same tumor set simultaneously at different test sites. Besides manufacturers' scoring criteria, the new American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines were used to interpret HER2 status. The concordance between CISH and FISH for positive and negative results was 98.5% at site A and 98.6% at site B using the manufacturers' criteria, and 99.0% at site A and 99.1% at site B using the ASCO/CAP criteria. Reproducibility of CISH results was more than 98.0% among 3 sites using the manufacturers' criteria and 100.0% between 2 sites using the ASCO/CAP criteria. Our results confirm that CISH is reliable for HER2 testing per ASCO/CAP guidelines.

2 Reads
  • Source
    • "<1.8), equivocal (1.8–2.2), and amplified (>2.2) according to ASCO/CAP guidelines [1] [13] "
    [Show abstract] [Hide abstract]
    ABSTRACT: The purpose was to evaluate and compare 5 different HER2 genetic assays with different characteristics that could affect the performance to analyze the human epidermal growth factor 2 (HER2) gene copy number under low and high throughput conditions. The study included 108 tissue samples from breast cancer patients with HER2 immunohistochemistry (IHC) results scored as 0/1+, 2+, and 3+. HER2 genetic status was analysed using chromogenic in situ hybridization (CISH) and fluorescence in situ hybridization (FISH). Scoring results were documented through digital image analysis. The cancer region of interest was identified from a serial H&E stained slide following tissue cores were transferred to a tissue microarrays (TMA). When using TMA in a routine flow, all patients will be tested for HER2 status with IHC followed by CISH or FISH, thereby providing individual HER2 results. In conclusion, our results show that the differences between the HER2 genetic assays do not have an effect on the analytic performance and the CISH technology is superior to high throughput HER2 genetic testing due to scanning speed, while the IQ-FISH may still be a choice for fast low throughput HER2 genetic testing.
    12/2013; 2013:368731. DOI:10.1155/2013/368731
  • Source
    • "They compared the results between FISH and CISH using the manufacturer's criteria (nonamplified and amplified) and the ASCO/CAP criteria (nonamplified, equivocal, and amplified). The concordance between CISH and FISH for positive and negative results was 98.5% and 98.6% at the two institutions using the manufacturers' criteria and 99% and 99.1% using the ASCO/CAP criteria [195]. The advantages of CISH include ability to analyze the test by light microscopy, preservation of morphologic features, permanent signals which will not fade with slide storage, lower reagent costs, and need for less expertise than FISH [193, 196]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Human epidermal growth factor receptor 2 (HER2) is an important prognostic and predictive factor in breast cancer. HER2 is overexpressed in approximately 15%-20% of invasive breast carcinomas and is associated with earlier recurrence, shortened disease free survival, and poor prognosis. Trastuzumab (Herceptin) a "humanized" monoclonal antibody targets the extracellular domain of HER2 and is widely used in the management of HER2 positive breast cancers. Accurate assessment of HER2 is thus critical in the management of breast cancer. The aim of this paper is to present a comprehensive review of HER2 with reference to its discovery and biology, clinical significance, prognostic value, targeted therapy, current and new testing modalities, and the interpretation guidelines and pitfalls.
    Pathology Research International 01/2011; 2011:903202. DOI:10.4061/2011/903202
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study specifically addressed the performance of chromogenic in situ hybridization (CISH) on HER2 testing in 66 breast carcinomas with chromosome 17 polysomy and 49 carcinomas with an equivocal HercepTest (DakoCytomation, Carpinteria, CA) score by comparing CISH with corresponding FISH results at 2 test sites and evaluating intersite agreement of CISH results. For tumors with chromosome 17 polysomy, when using the manufacturers' criteria, the concordance values between CISH and FISH at site A, site B, and intersite CISH agreement were 95.8%, 95.5%, and 93.5%, respectively; when using the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria, the values were 100.0%, 100.0%, and 100.0%, respectively. For tumors with an equivocal HercepTest score, when using the manufacturers' criteria, the concordance values between the 2 methods at site A, site B, and intersite CISH agreement were 88.2%, 95.1%, and 91.1%, respectively; when using the ASCO/CAP criteria, the values were 96.7%, 97.3%, and 97.4%, respectively. These results indicate that CISH is reliable for testing these 2 types of tumors, especially when the ASCO/CAP criteria are used.
    American Journal of Clinical Pathology 09/2009; 132(2):228-36. DOI:10.1309/AJCP4M2VUZCLDALN · 2.51 Impact Factor
Show more