Breast cancer and aneusomy 17: implications for carcinogenesis and therapeutic response

Reinholz, Monica M.; Bruzek, Amy K.; Visscher, Daniel W.; Lingle, Wilma L.; Schroeder, Melanie; Perez, Edith A.; Jenkins, Robert B.

doi:10.1016/s1470-2045(09)70063-4

Cited by 90 publications

(93 citation statements)

References 71 publications

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“…However, the most accurate method of assessing HER2 status is yet to be determined, and interpretation guidelines 3 as given by American Society of Clinical Oncology/College of American Pathologists may give conflicting results, depending Although this appears rather straightforward, abnormalities of chromosome 17 in breast cancer are frequent and may include whole chromosome copy number gains (polysomy 17) or losses (monosomy 17), focal copy number gains and losses, and other structural rearrangements. 10 These abnormalities of chromosome 17 can lead to discrepant interpretations of FISH data, depending on which criterion is used.…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12][13] In a recently published series by Vanden Bempt et al, >40% of breast carcinomas were found to harbor increased CEP17 copy number.…”

Section: Discussionmentioning

confidence: 99%

“…8,9 However, the reported frequency of CEP17 copy number alteration in breast cancer varies, depending on the study population, selection criteria, and the definition of chromosome 17 polysomy (CEP17). [10][11][12][13] In the literature, it is commonly assumed that an increase in CEP17 copy number is because of polysomy 17, and these terms have been used interchangeably. However, it is important to recognize that an increase in CEP17 signals does not necessarily represent a true polysomy (ie, gain of the entire chromosome), but rather may represent a focal pericentromeric gain or a partial polysomy.…”

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confidence: 99%

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Assessment of HER2 gene status in breast carcinomas with polysomy of chromosome 17

Vranić

Teruya

Repertinger

et al. 2010

Cancer

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BACKGROUND:The current study was performed to determine the impact of polysomy 17 on the interpretation of HER2 testing of invasive breast carcinomas using fluorescent in situ hybridization methods. Current American Society of Clinical Oncology/College of American Pathologists guidelines define HER2-positive tumors as those with >6 HER2 genes per nucleus or those with HER2/CEP17 (chromosome 17) ratio >2.2. These guidelines are potentially contradictory in tumors with polysomy of chromosome 17. METHODS: Seventy-two breast carcinoma cases with reported polysomy of chromosome 17 (3 CEP17 signals on average) by fluorescent in situ hybridization were identified, and the corresponding HER2 immunohistochemistry was obtained. The HER2 status of the archived samples was reviewed, and the tumors were recategorized according to the 2007 American Society of Clinical Oncology/College of American Pathologists guidelines. RESULTS: The average CEP17 copy number for the group was 4.5 (range, 3.0-10.4). Thirty-three (45.8%) cases had >6 copies of HER2 per nucleus. Twenty-one cases (29.2%) qualified as HER2 gene amplified using the HER2/CEP17 ratio (>2.2) guideline. All these cases had >6 HER2 signals, which represented 63.6% of all cases with >6 HER2 signals. HER2 protein expression showed significant positive correlations with both HER2 gene copy number and HER2/CEP17 ratio (P < .01, r s ¼ 0.56 and 0.64, respectively). CONCLUSIONS: Increased CEP17 signals detected in invasive breast carcinomas may lead to discordant interpretation of gene amplification in a significant proportion of the cases, depending on which criterion (ratio vs absolute number) is used for interpretation. However, increased gene dosage (>6 HER2 genes or HER2/CEP17 ratio >2.2), regardless of the evaluation method, is positively correlated with HER2 protein expression. Cancer 2011;117:48-53.

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Section: Discussionmentioning

confidence: 99%

“…[10][11][12][13] In a recently published series by Vanden Bempt et al, >40% of breast carcinomas were found to harbor increased CEP17 copy number.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Assessment of HER2 gene status in breast carcinomas with polysomy of chromosome 17

Vranić

Teruya

Repertinger

et al. 2010

Cancer

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“…However, in breast cancer, monosomy of centromere 17 (Cep17), unlike polysomy, has been shown to be a rare event. 12 Few studies are available on the correlation of chromosome 17 abnormalities with prognostic and predictive parameters in invasive breast cancer.…”

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confidence: 99%

Centromere 17 Copy Number Alteration: Negative Prognostic Factor in Invasive Breast Cancer?

Petroni

Addati²,

Mattioli³

et al. 2012

Archives of Pathology &Amp; Laboratory Medicine

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N Context.-Chromosome 17 polysomy has been identified in 5% to 50% of invasive breast cancers; even though a relationship with human epidermal growth factor receptor 2 (HER2/neu) status has been reported, other studies have shown that coincident centromere 17 (Cep17) amplification may be the cause of an overestimation of chromosome 17 polysomy in fluorescence in situ hybridization (FISH) testing.Objective.-To evaluate polysomy/amplification of Cep17 in invasive breast cancer with relation to proliferative activity (Ki-67), estrogen receptor, progesterone receptor, and HER2/neu status, in an attempt to identify a subgroup of patients with a worse prognosis.Design.-A total of 647 cases of invasive ductal breast cancer were collected and subjected to FISH analysis for HER2/neu gene and centromere 17 alteration, HercepTest for HER2/neu protein expression, and routine immunohistochemistry for Ki-67 and hormone receptor status.Results.-Copy number gain of Cep17 was observed in 27.3% of cases. Within this group, HER2/neu gene amplification was detected in 14.1% of cases, whereas HER2/neu expression was scored 3+ in 20.1% of cases; about half of the HER2/neu overexpressing cases (9.8%) did not show amplification by FISH. Moreover, 69% of polysomic cases showed high Ki-67 index.Conclusions.- (1) Centromere 17-altered cases are frequently HER2/neu overexpressing but not amplified, resulting in HercepTest/FISH disagreement; (2) HER2/neu amplification is seen at a higher incidence in cases without Cep17 copy number alterations, which are therefore not necessarily due to chromosome 17 disorder; (3) proliferation index is significantly higher in aneusomic tumors. These data suggest that the presence of Cep17 alterations could identify a subset of breast cancers with more aggressive biological and clinical behavior, which may show nonresponsiveness to conventional therapy independently of HER2/neu amplification status.

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“…El caso 28 (carcinoma de mama) es interesante porque presentó monosomía del cromosoma 17, considerada una alteración cromosómica común durante el desarrollo de esta neoplasia (17,34). Es bien conocido que los genes BRCA1, HER2/ neu y el TP53 están asociados con la génesis del cáncer de mama (1,7,9,32).…”

Section: Discussionunclassified

Detección de aneuploidías del cromosoma 17 y deleción del gen TP53 en una amplia variedad de tumores sólidos mediante hibridación in situ fluorescente bicolor

et al. 2010

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Detección de aneuploidías del cromosoma 17 y deleción del genTP53 en una amplia variedad de tumores sólidos mediante hibridación in situ fluorescente bicolor Introducción. El TP53 es un gen supresor de tumores localizado en la región cromosómica 17p13.1; controla el ciclo celular y se encuentra alterado en cerca de 50% de todas las neoplasias. Objetivos. Determinar las aneuploidías del cromosoma 17 y la deleción en el locus 17p13.1 del gen TP53, en diversos tumores sólidos primarios utilizando la técnica FISH-bicolor. Materiales y métodos. Se analizaron 38 muestras de diversos tipos de tumores sólidos primarios. Todas las muestras se disociaron mecánica y enzimáticamente con colagenasa al 0,2%, antes de la obtención de los núcleos interfásicos. La técnica de FISH-bicolor se realizó en núcleos interfásicos, mediante sondas marcadas directamente con fluorocromos para el centrómero del cromosoma 17 (CEP 17; señal verde; VYSIS) y para el locus específico del gen TP53 (LSI 17p13.1; señal naranja; VYSIS). Resultados. Se encontró que 63% (24/38) de las muestras tenían aneuploidías del cromosoma 17. La monosomía fue la aneuploidía más frecuente (75%; 18/24), seguida de la trisomía (17%; 4/24); la nulisomía y la tetrasomía fueron menos frecuentes. El 89,5% (34/38) de los casos presentaron deleción del gen TP53. Sólo cuatro casos fueron normales para el número de copias del cromosoma 17 y del gen TP53. El estudio histopatológico mostró que la mayoría de las muestras eran tumores malignos. Conclusiones. La aneuploidía del cromosoma 17 y la deleción en el locus 17p13.1 del gen TP53 son alteraciones muy frecuentes en los tumores sólidos. La técnica FISH-bicolor permite detectar simultáneamente alteraciones cromosómicas numéricas y estructurales en núcleos interfásicos.Palabras clave: aneuploidía, deleción cromosómica, gen Tp53, hibridación fluorescente in situ, neoplasias, inestabilidad cromosómica, heterogeneidad genética. Detection of chromosome 17 aneuplody and TP53 gene deletion in a broad variety of solid tumors by dual-color fluorescence in situ hybridization (FISH)Introduction. TP53 is a tumor suppressor gene located on chromosome 17p13.1. This gene is essential for the control of cell cycle and has been found altered in about 50% of all tumor types. Objective. The presence of aneuploidy of chromosome 17 and TP53 gene deletion at 17p13.1 locus was determined in primary solid tumors using the dual-color FISH (fluorescence in situ hybridization). Materials and methods. Thirty-eight samples consisted of several types of primary solid tumors. All samples were mechanically and enzymatically disaggregated with 0.2% collagenase prior to obtaining interphase nuclei. The dual-color FISH was performed using direct fluorescent labeling probes for the chromosome 17 centromere (green signal) and for the TP53 gene locus-specific (orange signal).Results. Characteristic aneuploidy on chromosome 17 was found in 63% (24/38) of the samples. Monosomy occurred most frequently (75%, 18/24), followed by trisomy (17%, 4/24); nullisomy and te...

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Breast cancer and aneusomy 17: implications for carcinogenesis and therapeutic response

Cited by 90 publications

References 71 publications

Assessment of HER2 gene status in breast carcinomas with polysomy of chromosome 17

Assessment of HER2 gene status in breast carcinomas with polysomy of chromosome 17

Centromere 17 Copy Number Alteration: Negative Prognostic Factor in Invasive Breast Cancer?

Detección de aneuploidías del cromosoma 17 y deleción del gen TP53 en una amplia variedad de tumores sólidos mediante hibridación in situ fluorescente bicolor

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