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Jan F Silverman - One of the best experts on this subject based on the ideXlab platform.
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poor prognostic significance of unamplified Chromosome 17 polysomy in invasive breast carcinoma
Modern Pathology, 2009Co-Authors: Uma Krishnamurti, Jennifer L Hammers, Folefac D Atem, Patrick Storto, Jan F SilvermanAbstract:The human epidermal growth factor receptor 2 (HER2) oncoprotein is overexpressed in about 20% of breast cancers, with HER2 gene amplification responsible for protein overexpression in the vast majority of patients. A subset of breast cancers have Chromosome 17 aneusomy, due to either 17 monosomy (a single copy of Chromosome 17) or polysomy (increased copy numbers of Chromosome 17). Although HER2 overexpression is an established adverse prognostic factor in breast cancer, the role of unamplified Chromosome 17 polysomy is uncertain and there is a paucity of literature on the correlation of Chromosome 17 aneusomy with important prognostic and predictive pathologic factors in invasive breast carcinoma. Furthermore, while patients showing HER2 amplification with or without polysomy 17 are treated with trastuzumab with or without other chemotherapy, treatment of patients with unamplified Chromosome 17 polysomy is not well defined. Currently most of these patients are treated similar to patients with neither amplification nor 17 polysomy. The aim of this study was to compare some prognostic and predictive factors in invasive breast carcinoma in patients with unamplified Chromosome 17 polysomy with that seen in cases with HER2 gene amplification and those with neither amplification or polysomy. We found that invasive breast carcinomas with unamplified Chromosome 17 polysomy are associated with several adverse prognostic indicators such as a higher nuclear grade, mitotic activity, Nottingham score, histologic grade, tumor stage, and greater estrogen receptor negativity with a trend towards the amplified group, in contrast to patients with neither amplification or polysomy. Although most patients with unamplified 17 polysomy have a 2+ equivocal score on immunohistochemistry, a minority has a 3+ positive score. An increased adverse role for unamplified polysomy along with 3+ protein expression in some patients supports the idea that these patients should be considered for therapy with trastuzumab and/or anthracyclines.
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Poor prognostic significance of unamplified Chromosome 17 polysomy in invasive breast carcinoma.
Modern Pathology, 2009Co-Authors: Uma Krishnamurti, Jennifer L Hammers, Folefac D Atem, Patrick Storto, Jan F SilvermanAbstract:Poor prognostic significance of unamplified Chromosome 17 polysomy in invasive breast carcinoma
Paul J. Van Diest - One of the best experts on this subject based on the ideXlab platform.
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Chromosome 17 copy number changes in male breast cancer
Cellular Oncology, 2015Co-Authors: Miangela M. Lacle, Cathy B. Moelans, Robert Kornegoor, Arjen J. Witkamp, Elsken Van Der Wall, Josef Rueschoff, Horst Buerger, Paul J. Van DiestAbstract:Background Overall, HER2-amplified female breast cancer (FBC) is associated with a high grade, an aggressive phenotype and a poor prognosis. In male breast cancer (MBC) amplification of HER2, located on Chromosome 17, occurs at a lower frequency than in FBC, where it is part of complex rearrangements. So far, only few studies have addressed the occurrence of Chromosome 17 alterations in small MBC cohorts.
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Absence of Chromosome 17 polysomy in breast cancer: analysis by CEP17 chromogenic in situ hybridization and multiplex ligation-dependent probe amplification
Breast Cancer Research and Treatment, 2010Co-Authors: Cathy B. Moelans, Roel A. Weger, Paul J. Van DiestAbstract:Amplification of the HER2 gene, present in 15–30% of breast carcinomas, correlates with poor outcome and is an indication for treatment with trastuzumab. Standard testing methods for HER2 amplification are fluorescence (FISH) or chromogenic in situ hybridization (CISH). In FISH/CISH scoring, correction for Chromosome 17 polysomy is believed to be critical for determination of true HER2 amplification as opposed to increased Chromosome 17 copy number. The term “polysomy 17” is widely used and defined as ≥3 copies of the Chromosome 17 centromere (probe CEP17, D17Z1). Thus, the centromere is assumed to be representative for the entire Chromosome. This study aimed to investigate the frequency of polysomy 17 and its association with HER2 amplification in 111 invasive breast cancer patients by CEP17 CISH and by copy number analysis of a set of 17 genes along Chromosome 17 using multiplex ligation-dependent probe amplification (MLPA). Chromosome 17 usually showed a complex pattern of gains and losses by MLPA, unrelated to the copy number status of the centromere. Increase in centromere 17 copy number (denoted “polysomy 17”), as assessed by CEP17 CISH, was found in 19% of the patients. Of these patients, 60% also showed amplification of HER2 measured by MLPA. However, none of the 111 patients showed a true polysomy of Chromosome 17 by MLPA. Only two patients (1.8%) had a possible gain of 17q. Amplification of 17p was not found in any of the patients, although a possible loss of 17p was found in one patient. In conclusion, this extensive analysis of amplicons along Chromosome 17 shows that true polysomy of Chromosome 17, either of the whole Chromosome or of the short or the long arm, is very rare in invasive breast cancer. Abnormal CEP17 copy numbers may therefore actually stem from high level gains or amplification of CEP17 regardless of copy number gains of the short and long arms of Chromosome 17 and, at least in some cases, correction with CEP17 probes may provide misleading HER2 gene status assessment results.
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absence of Chromosome 17 polysomy in breast cancer analysis by cep17 chromogenic in situ hybridization and multiplex ligation dependent probe amplification
Breast Cancer Research and Treatment, 2010Co-Authors: Cathy B. Moelans, Roel A. Weger, Paul J. Van DiestAbstract:Amplification of the HER2 gene, present in 15–30% of breast carcinomas, correlates with poor outcome and is an indication for treatment with trastuzumab. Standard testing methods for HER2 amplification are fluorescence (FISH) or chromogenic in situ hybridization (CISH). In FISH/CISH scoring, correction for Chromosome 17 polysomy is believed to be critical for determination of true HER2 amplification as opposed to increased Chromosome 17 copy number. The term “polysomy 17” is widely used and defined as ≥3 copies of the Chromosome 17 centromere (probe CEP17, D17Z1). Thus, the centromere is assumed to be representative for the entire Chromosome. This study aimed to investigate the frequency of polysomy 17 and its association with HER2 amplification in 111 invasive breast cancer patients by CEP17 CISH and by copy number analysis of a set of 17 genes along Chromosome 17 using multiplex ligation-dependent probe amplification (MLPA).
John M. S. Bartlett - One of the best experts on this subject based on the ideXlab platform.
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Chromosome 17 ANEUSOMY IS ASSOCIATED WITH POOR PROGNOSTIC FACTORS IN INVASIVE BREAST CARCINOMA
Breast Cancer Research and Treatment, 2020Co-Authors: A.d. Watters, James J. Going, Timothy G. Cooke, John M. S. BartlettAbstract:Aberrations of Chromosome 17 are common in breast cancer. Fluorescence in situ hybridization (FISH) enables gene or Chromosome copy number to be assessed in situ in archival tissues and related to morphology and clinical outcome. In this study direct labeled DNA probes for the Chromosome 17 alpha satellite and the HER2/neu gene were applied simultaneously to 5 micron sections of 214 formalin-fixed paraffin-embedded invasive primary breast carcinomas. A high proportion (54%) of invasive breast carcinomas displayed aneusomy of Chromosome 17. Polysomy 17 correlated with multiple copies of HER2/neu (p =
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Determination of HER2 amplification by in situ hybridization: when should Chromosome 17 also be determined?.
Cancer Research, 2009Co-Authors: John M. S. Bartlett, Fiona Campbell, Elizabeth MallonAbstract:CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #3002 Introduction: Aberrations of Chromosome 17 (aneusomy) are common in breast cancerand therefore have a critical impact on the assessment and reporting of HER2 gene amplification in a significant sub-set of cases. There is an ongoing debate as to the proportion of cases for which assessment of Chromosome 17 copy number may be important. According to current guidelines1,2, amplification of HER2 is considered to be a HER2/Chromosome 17 ratio ≥2.0 and a ratio 6.0 reflect amplification and a result of
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determination of her2 amplification by in situ hybridization when should Chromosome 17 also be determined
Cancer Research, 2009Co-Authors: John M. S. Bartlett, Fiona Campbell, Elizabeth MallonAbstract:CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #3002 Introduction: Aberrations of Chromosome 17 (aneusomy) are common in breast cancerand therefore have a critical impact on the assessment and reporting of HER2 gene amplification in a significant sub-set of cases. There is an ongoing debate as to the proportion of cases for which assessment of Chromosome 17 copy number may be important. According to current guidelines1,2, amplification of HER2 is considered to be a HER2/Chromosome 17 ratio ≥2.0 and a ratio 6.0 reflect amplification and a result of <4.0 HER2 gene copies per nucleus is always associated with lack of amplification; cases with 4-6 copies per cell are thought to require validation by testing of a parallel section for Chromosome 171,2. To our knowledge, this assumption has not been verified experimentally. Methods: HER2 and Chromosome 17 were measured by dual color FISH in 1711 breast cancer samples referred to the authors laboratories between 2000-2008. Using HER2 copy number and Chromosome 17 data the impact of Chromosome 17 testing upon accuracy of diagnosis of gene amplification was assessed. Results: At a HER2 copy number of 2 to <3, 16 of 488 cases (3.3%) had HER2 amplification; and at a copy number of 3 to <4, 32 of 195 cases (16.4%) were amplified. The proportion of cases with HER2 amplification increased considerably at HER2 copy numbers of 4 to <7: 50.0% at 4 to <5; 67.5% at 5 to <6, and 77.3% at 6 to <7. Virtually all cases were amplified at HER2 copy numbers of ≥7. Conclusion: Werecommend that all cases with observed HER2 copy numbers of 2 to 7 should also be analyzed for Chromosome 17 in order to accurately determine HER2 gene amplification. This would require analysis of Chromosome 17 in 48.3% of all breast cancer cases based upon the study population. Current guidelines1,2 recommend Chromosome 17 measurement only in cases with a HER2 copy number of 4 to <6, which represents only 6.6% of all breast cancer cases in the current study. Although single color ISH is becoming more widely used with the availability of CISH, the importance of Chromosome 17 measurement cannot be ignored. It is essential that HER2 testing is of high quality, so that optimal patient management can be provided. 1. Ellis IO, Bartlett J, Dowsett M et al: Updated recommendations for HER2 testing in the UK. J.Clin.Path. 57(3), 233-237 (2004). 2. Wolff AC, Hammond ME, Schwartz JN et al: American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer. Journal of Clinical Oncology 25(1), 118-145 (2007). Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3002.
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Chromosome 17 aneusomy is associated with poor prognostic factors in invasive breast carcinoma
Breast Cancer Research and Treatment, 2003Co-Authors: A.d. Watters, James J. Going, Timothy G. Cooke, John M. S. BartlettAbstract:Aberrations of Chromosome 17 are common in breast cancer. Fluorescence in situ hybridization (FISH) enables gene or Chromosome copy number to be assessed in situ in archival tissues and related to morphology and clinical outcome. In this study direct labeled DNA probes for the Chromosome 17 alpha satellite and the HER2/neu gene were applied simultaneously to 5 micron sections of 214 formalin-fixed paraffin-embedded invasive primary breast carcinomas. A high proportion (54%) of invasive breast carcinomas displayed aneusomy of Chromosome 17. Polysomy 17 correlated with multiple copies of HER2/neu (p = <0.001), but not with HER2/neu amplification. Eighty-six patients without HER2/neu amplification had aneusomy 17. Fifty-eight of the 86 patients that had aneusomy 17 had high HER2/neu copy number. Twelve patients with normal copy number for Chromosome 17 had amplification of HER2/neu and 30 patients had amplification of HER2/neu with aneusomy 17. Aneusomy 17 was associated with grade 3 carcinoma (p = 0.008), ER negativity (p = 0.0032) and a Nottingham prognostic index of greater than 5.4 (p = 0.039) but was not associated with survival by univariate analysis. In conclusion, the determination of Chromosome 17 copy number should be incorporated in assessment of HER2/neu status, as this will give an accurate measure of amplification of HER2/neu and may also be helpful in determining suitability for breast carcinoma trials.
Cathy B. Moelans - One of the best experts on this subject based on the ideXlab platform.
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Chromosome 17 copy number changes in male breast cancer
Cellular Oncology, 2015Co-Authors: Miangela M. Lacle, Cathy B. Moelans, Robert Kornegoor, Arjen J. Witkamp, Elsken Van Der Wall, Josef Rueschoff, Horst Buerger, Paul J. Van DiestAbstract:Background Overall, HER2-amplified female breast cancer (FBC) is associated with a high grade, an aggressive phenotype and a poor prognosis. In male breast cancer (MBC) amplification of HER2, located on Chromosome 17, occurs at a lower frequency than in FBC, where it is part of complex rearrangements. So far, only few studies have addressed the occurrence of Chromosome 17 alterations in small MBC cohorts.
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Absence of Chromosome 17 polysomy in breast cancer: analysis by CEP17 chromogenic in situ hybridization and multiplex ligation-dependent probe amplification
Breast Cancer Research and Treatment, 2010Co-Authors: Cathy B. Moelans, Roel A. Weger, Paul J. Van DiestAbstract:Amplification of the HER2 gene, present in 15–30% of breast carcinomas, correlates with poor outcome and is an indication for treatment with trastuzumab. Standard testing methods for HER2 amplification are fluorescence (FISH) or chromogenic in situ hybridization (CISH). In FISH/CISH scoring, correction for Chromosome 17 polysomy is believed to be critical for determination of true HER2 amplification as opposed to increased Chromosome 17 copy number. The term “polysomy 17” is widely used and defined as ≥3 copies of the Chromosome 17 centromere (probe CEP17, D17Z1). Thus, the centromere is assumed to be representative for the entire Chromosome. This study aimed to investigate the frequency of polysomy 17 and its association with HER2 amplification in 111 invasive breast cancer patients by CEP17 CISH and by copy number analysis of a set of 17 genes along Chromosome 17 using multiplex ligation-dependent probe amplification (MLPA). Chromosome 17 usually showed a complex pattern of gains and losses by MLPA, unrelated to the copy number status of the centromere. Increase in centromere 17 copy number (denoted “polysomy 17”), as assessed by CEP17 CISH, was found in 19% of the patients. Of these patients, 60% also showed amplification of HER2 measured by MLPA. However, none of the 111 patients showed a true polysomy of Chromosome 17 by MLPA. Only two patients (1.8%) had a possible gain of 17q. Amplification of 17p was not found in any of the patients, although a possible loss of 17p was found in one patient. In conclusion, this extensive analysis of amplicons along Chromosome 17 shows that true polysomy of Chromosome 17, either of the whole Chromosome or of the short or the long arm, is very rare in invasive breast cancer. Abnormal CEP17 copy numbers may therefore actually stem from high level gains or amplification of CEP17 regardless of copy number gains of the short and long arms of Chromosome 17 and, at least in some cases, correction with CEP17 probes may provide misleading HER2 gene status assessment results.
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absence of Chromosome 17 polysomy in breast cancer analysis by cep17 chromogenic in situ hybridization and multiplex ligation dependent probe amplification
Breast Cancer Research and Treatment, 2010Co-Authors: Cathy B. Moelans, Roel A. Weger, Paul J. Van DiestAbstract:Amplification of the HER2 gene, present in 15–30% of breast carcinomas, correlates with poor outcome and is an indication for treatment with trastuzumab. Standard testing methods for HER2 amplification are fluorescence (FISH) or chromogenic in situ hybridization (CISH). In FISH/CISH scoring, correction for Chromosome 17 polysomy is believed to be critical for determination of true HER2 amplification as opposed to increased Chromosome 17 copy number. The term “polysomy 17” is widely used and defined as ≥3 copies of the Chromosome 17 centromere (probe CEP17, D17Z1). Thus, the centromere is assumed to be representative for the entire Chromosome. This study aimed to investigate the frequency of polysomy 17 and its association with HER2 amplification in 111 invasive breast cancer patients by CEP17 CISH and by copy number analysis of a set of 17 genes along Chromosome 17 using multiplex ligation-dependent probe amplification (MLPA).
Uma Krishnamurti - One of the best experts on this subject based on the ideXlab platform.
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poor prognostic significance of unamplified Chromosome 17 polysomy in invasive breast carcinoma
Modern Pathology, 2009Co-Authors: Uma Krishnamurti, Jennifer L Hammers, Folefac D Atem, Patrick Storto, Jan F SilvermanAbstract:The human epidermal growth factor receptor 2 (HER2) oncoprotein is overexpressed in about 20% of breast cancers, with HER2 gene amplification responsible for protein overexpression in the vast majority of patients. A subset of breast cancers have Chromosome 17 aneusomy, due to either 17 monosomy (a single copy of Chromosome 17) or polysomy (increased copy numbers of Chromosome 17). Although HER2 overexpression is an established adverse prognostic factor in breast cancer, the role of unamplified Chromosome 17 polysomy is uncertain and there is a paucity of literature on the correlation of Chromosome 17 aneusomy with important prognostic and predictive pathologic factors in invasive breast carcinoma. Furthermore, while patients showing HER2 amplification with or without polysomy 17 are treated with trastuzumab with or without other chemotherapy, treatment of patients with unamplified Chromosome 17 polysomy is not well defined. Currently most of these patients are treated similar to patients with neither amplification nor 17 polysomy. The aim of this study was to compare some prognostic and predictive factors in invasive breast carcinoma in patients with unamplified Chromosome 17 polysomy with that seen in cases with HER2 gene amplification and those with neither amplification or polysomy. We found that invasive breast carcinomas with unamplified Chromosome 17 polysomy are associated with several adverse prognostic indicators such as a higher nuclear grade, mitotic activity, Nottingham score, histologic grade, tumor stage, and greater estrogen receptor negativity with a trend towards the amplified group, in contrast to patients with neither amplification or polysomy. Although most patients with unamplified 17 polysomy have a 2+ equivocal score on immunohistochemistry, a minority has a 3+ positive score. An increased adverse role for unamplified polysomy along with 3+ protein expression in some patients supports the idea that these patients should be considered for therapy with trastuzumab and/or anthracyclines.
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Poor prognostic significance of unamplified Chromosome 17 polysomy in invasive breast carcinoma.
Modern Pathology, 2009Co-Authors: Uma Krishnamurti, Jennifer L Hammers, Folefac D Atem, Patrick Storto, Jan F SilvermanAbstract:Poor prognostic significance of unamplified Chromosome 17 polysomy in invasive breast carcinoma