Chromogenic In Situ Hybridization to Detect HER-2/<i>neu</i> Gene Amplification in Histological and ThinPrep®-Processed Breast Cancer Fine-Needle Aspirates: A Sensitive and Practical Method in the Trastuzumab Era

Vocaturo, Amina; Novelli, Flavia; Benevolo, Maria; Piperno, Giulia Maria; Marandino, Ferdinando; Cianciulli, Anna Maria; Merola, Roberta; Donnorso, R. Perrone; Sperduti, Isabella; Buglioni, Simonetta; Mottolese, Marcella

doi:10.1634/theoncologist.11-8-878

Cited by 49 publications

(24 citation statements)

References 29 publications

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“…In current practice, the use of HercepTest™ is considered insufficient in patients with, for example, a HER-2 2ϩ outcome. Equivocal IHC samples (2ϩ) must be retested for HER-2 amplification by FISH or CISH [13]. Equivocal FISH or CISH results must be confirmed by counting additional cells or repeating the test with a different method.…”

Section: Molecular Pathologic Diagnosismentioning

confidence: 99%

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Trastuzumab

2011

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Trastuzumab is standard of care in the treatment of human epidermal growth factor receptor (HER)-2 ؉ early and advanced breast cancer. Recently, it has been approved for the treatment of HER-2 ؉ advanced gastric cancer. Trastuzumab is an IgG1 humanized monoclonal antibody administered by intravenous infusion on a weekly or three weekly schedule. In all registered indications, trastuzumab is almost always given in combination with chemotherapy. In hormonal receptorpositive breast cancer in postmenopausal women, trastuzumab can be combined with an aromatase inhibitor. Main toxicity is reduction in the left ventricular ejection fraction, which in a minority of patients can become symptomatic, but in many patients is at least partly reversible. Long-term safety needs to be further determined. The Oncologist 2011;16:800 -810

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Section: Molecular Pathologic Diagnosismentioning

confidence: 99%

“…The pathologist scores the test as 0, 1ϩ, 2ϩ, or 3ϩ, and only 3ϩ and/or showing HER-2 amplification by FISH or CISH identifies patients for trastuzumab treatment. In the case of gastric cancer a 3ϩ IHC score combined with a positive FISH result is considered necessary for trastuzumab treatment [13]. …”

Section: Molecular Pathologic Diagnosismentioning

confidence: 99%

Trastuzumab

2011

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“…17,23,29 But others reported significant higher rates. 19,30 Possible explanations for these results could be attributed to variation in time of fixation, processing condition and use of different manufacturers kits. In this current study CISH assay showed amplification of the HER-2 neu gene in 30% of cases.…”

Section: Resultsmentioning

confidence: 99%

“…It is also practical, cost effective and convenient to perform as it does not require special equipment like fluorescence microscope and much experience in interpreting results. 19 Direct evaluation of gene amplification using CISH assay is a reliable method for routine diagnostic evaluation of HER2/neu status in breast cancer patients, especially in specimens showing 2+ IHCscore. 20 There are two methods of CISH assay: Standard CISH, which uses an HER-2 probe only and dual-color CISH (dc-CISH), which uses a HER-2 probe and a CEN17 (chromosome 17 centromere) probe.…”

Section: Introductionmentioning

confidence: 99%

Determination of HER-2/neu gene Status by Chromogenic in Situ Hybridisation Assay on Borderline (2+) Immunohistochemistry Cases in Patients with Invasive Breast Carcinoma: An Experimental Study on Preserved Tissue

Khanam

Chowdhury

Banu

et al. 2018

Bangladesh Med Res Counc Bull

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HER-2 (also known as HER-2/neu) is a member of the epidermal growth factor (EGF) receptor family. The amplification of oncogene HER-2 is presented in 20 to 30% of breast cancers and results in an increase of the protein expression. HER-2 over expression has also been shown to correlate with poor prognosis. It is associated with poorly differentiated high grade tumors with lymph node involvement, greater risk of recurrence and relative resistance to some types of chemotherapy. The receptor is however a target for treatment with anti HER-2 antibody trastuzumab (Herceptin). Immunohistochemistry analysis for HER 2 scoring is subjective, requires trained personnel and expertise. One of the main concerns with IHC is that there is evidence of significant inter-observer variation in the assessment of staining, which can lead to misclassification of HER2 status. Chromogenic in situ hybridisation (CISH) testing is sensitive and specific in detecting HER-2/neu gene amplification. Direct evaluation of gene amplification using CISH assay is a reliable method for routine diagnostic evaluation of HER2/neu status in breast cancer patients, especially in specimens showing 2+ IHC score. This observational experimental study was carried out in the Department of Pathology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, during the period of July 2014 to June 2015, The aim of this study was to assess HER-2 expression accurately in equivocal immunohistochemistry (2+) invasive breast cancer cases by Chromogenic in situ hybridisation and to associate the findings of CISH assay with the histologic prognostic and predictive factors (eg: tumor size, regional lymph node metastases, tumor grade and type. A total of 20 archival paraffin tissue blocks and IHC slides with IHC score 2+ for HER-2 were included in this study. All the slides were reviewed. CISH assay was done on section from archival paraffin block.CISH assay showed amplification of the HER-2 neu gene in 30% of cases. Majority (60%) was nonamplified. In two cases the results were unsatisfactory for interpretation. The differences were not statistically significant (p>0.05) among three groups (amplified, nonamplified and unsatisfactory) regarding the baseline characteristics (age and sex) with CISH. All the results of CISH assay in association with tumor size, tumor grade and lymphnode metastasis were not statistically significant. HER-2 / neu status is the one of the most important prognostic and predictive factor. It is a target for treatment with anti HER-2 antibody trastuzumab (Herceptin). Detection of HER-2/ neu status by IHC may sometimes be difficult and inaccurate, specially in IHC score 2+ cases. Based on the findings of the study, CISH can be considered as a useful, simple and reproducible method for detecting HER-2/ neu gene amplification in cases with borderline (2+) immunohistochemistry score and patients may be benefited from Trastuzumab therapy.

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“…Using a residual LBC sample remaining in a vial, additional tests (immunocytochemistry and gene analysis) can be performed, increasing the diagnostic accuracy [11][12][13][14][15][16]. However, increased staining intensity of the nuclear chromatin and nuclear size reduction in LBC samples may make cancer cell judgment difficult in well-differentiated adenocarcinoma lacking atypia [17][18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Usefulness of Evaluation of Nuclear Color by Visible-Microscopic Spectroscopy for Objective Differentiation between Non-Cancer and Cancer Cells Prepared Using Liquid-Based Cytology

Yoshioka¹,

Hoshiai²,

Nakamura³

et al. 2015

J Cytol Histol

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Objective: The aims of this study were to investigate the usefulness of color evaluation of the nuclear region using visible-microscopic spectroscopy (Vis-MS) and to clarify whether it can serve as an index to distinguish cancer cells in liquid-based cytology (LBC). Vis-MS is a spectral analysis technique widely used for absorption and fluorometric analyses in the analytical chemistry field. Vis-MS has been applied to histological diagnosis, but only a few studies on its application to cytology have been performed, and no investigations have been performed for LBC, which is expected to become widely used in Japan. Study design: Using culture cell lines of non-cancer cells and cancer cells, transmittance at 530 nm (maximum absorption wavelength of eosin), 580 nm (hematoxylin), and 630 nm (light green), and 530 nm/580 nm and 630 nm/580 nm transmittance ratios were analyzed.Results: Two variances of the transmittance at 580 nm and 630 nm/580 nm transmittance ratio were finally extracted as effective items after applying forward and backward variance selection and investigation of multicollinearity. The odds ratios of 580 nm transmittance and 630 nm/580 nm transmittance ratio were 0.48 and 0.72, respectively. The cancer cell discrimination predictive value determined using the logistic regression equation was 98.0%, being favorable. Conclusion:It was suggested that Vis-MS is useful to evaluate the color of the nuclear region and serves as a cancer cell discrimination index for LBC. We are planning to apply Vis-MS to clinical materials and develop nuclear color evaluation using Vis-MS into an objective index for cases in which cancer cell judgment is difficult.

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Chromogenic In Situ Hybridization to Detect HER-2/neu Gene Amplification in Histological and ThinPrep®-Processed Breast Cancer Fine-Needle Aspirates: A Sensitive and Practical Method in the Trastuzumab Era

Cited by 49 publications

References 29 publications

Trastuzumab

Trastuzumab

Determination of HER-2/neu gene Status by Chromogenic in Situ Hybridisation Assay on Borderline (2+) Immunohistochemistry Cases in Patients with Invasive Breast Carcinoma: An Experimental Study on Preserved Tissue

Usefulness of Evaluation of Nuclear Color by Visible-Microscopic Spectroscopy for Objective Differentiation between Non-Cancer and Cancer Cells Prepared Using Liquid-Based Cytology

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