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J Pathol Transl Med : Journal of Pathology and Translational Medicine

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2 "Polysomy"
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Case Report
HER2-Positive Breast Carcinomas with Co-amplification or Gain of Chromosome 17 Centromere Locus: Report of Three Cases and an Impact on HER2 Testing.
Hyeong Chan Shin, Young Kyung Bae, Aeri Kim, Seok Ju Park
Korean J Pathol. 2011;45(6):665-669.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.665
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AbstractAbstract PDF
Recently we experienced three cases of human epidermal growth factor receptor 2 (HER2)-amplified invasive breast carcinomas associated with co-amplification or gain of chromosome 17 centromere (CEP17) in silver-enhanced in situ hybridization (SISH) analysis. These cases revealed 2+ or 3+ staining for HER2 immunohistochemistry and >6 HER2 copies per cell on SISH analyses. However, the calculated HER2/CEP17 ratios were low (<2.2) and did not fit within the HER2-positive category. We interpreted those cases as HER2-positive tumors based on the number of HER2 copies per cell. There is a potential for misinterpretation of SISH analysis in cases showing increased CEP17 copy number, based on the criterion used for HER2 positivity (HER2 copies >6 per cell vs HER2/CEP17 ratio>2.2). We recommend reporting raw SISH or fluorescence in situ hybridization data, including number of cells counted, average numbers of HER2 and CEP17 signals, and the calculated HER2/CEP17 ratio to prevent underreporting of HER2 amplification.
Original Article
Detection of Numerical Chromosomal Aberration in Squamous Cell Carcinoma of the Lung by In Situ Hybridization Using #17 Centromeric Probes.
Sang Sook Lee, Seong Beom Han, Soong Kook Park
Korean J Pathol. 1993;27(5):443-458.
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AbstractAbstract PDF
This study was carried out to understand the relationship between specific chromosome changes and their phenotypic consequences at the tissue level of human lung cancers. Then paraffin-embedded human lung squamous cell carcinoma samples were investigated for in evidence of genetic alterations, using chromosome 7 and 17-specific repetitive alpha-satellite DNA probes. In situ hybridization procedure with chromosome-specific DNA probes was optimized for use on formalin-fixed paraffin-embedded lung tissue sections. The chromosome index ranged from 1.10 to 1.88(median, 1.49) for chromosome 7 and 1.20 to 1.98(median, 1.69) for chromosome 17. Normal lymphocytes and stromal cells showed one or two chromosome signals per cell in most cases. All tumors showed three or more chromosome signals per cell with range of 16.0% to 80.6% of cancer cells(median, 50.9%) for chromosome 7 and 32.7% to 84.7%(median, 69.9%) for chromosome 17. The chromosome index did not correlate with the DNA content in most cases. Chromosomes 7 and 17 were either overrepresented or underrepresented when they were compared with corresponding DNA index determined by FCM. An increase in copy number, particularly of chromosome 7 was associated with a less favorable phenotype, including high nuclear grade. In addition, chromosome alterations were differentially expressed in the different areas of the same tissue section, correlating with histologic heterogeneity. These results suggest that chromosome polysomy can be reliably detected in tissue sections using in situ hybridization. There is a strong correlation between genotypic abnormalities and tumor phenotype in human lung cancer. This capability will prove to be an important tool for determining the underlying genetic basis for tumor development, tissue phenotype heterogeneity and progression by allowing genetic determination to be made on paraffin-embedded tissue sections where tumor histologic architecture is preserved.

J Pathol Transl Med : Journal of Pathology and Translational Medicine