The Experts below are selected from a list of 132477 Experts worldwide ranked by ideXlab platform

Robert W Akita - One of the best experts on this subject based on the ideXlab platform.

  • her 2 neu expression in node negative breast cancer direct tissue quantitation by computerized image analysis and association of overexpression with increased risk of Recurrent Disease
    Cancer Research, 1993
    Co-Authors: Michael F Press, Malcolm C Pike, Victoria R Chazin, Gene Hung, Judith A Udove, Mitchell Markowicz, John Danyluk, William Godolphin, Mark X Sliwkowski, Robert W Akita
    Abstract:

    Abstract The HER-2/ neu proto-oncogene (also known as c- ceb B-2) is homologous with, but distinct from, the epidermal growth factor receptor. Amplification of this gene in node-positive breast cancers has been shown to correlate with both earlier relapse and shorter overall survival. In node-negative breast cancer patients, the subgroup for which accurate prognostic data could make a significant contribution to treatment decisions, the prognostic utility of HER-2/ neu amplification and/or overexpression has been controversial. The purpose of this report is to address the issues surrounding this controversy and to evaluate the prognostic utility of overexpression in a carefully followed group of patients using appropriately characterized reagents and methods. In this report we present data from a study of HER-2/ neu expression designed specifically to test whether or not overexpression is associated with an increased risk of recurrence in node-negative breast cancers. From a cohort of 704 women with node-negative breast cancer who experienced Recurrent Disease (relapsed cases) 105 were matched with 105 women with no recurrence (Disease-free controls) after the equivalent follow-up period. Immunohistochemistry was used to assess HER-2/ neu expression in archival tissue blocks from both relapsed cases and their matched Disease-free controls. Importantly, a series of molecularly characterized breast cancer specimens were used to confirm that the antibody used was of sufficient sensitivity and specificity to identify those cancers overexpressing the HER-2/ neu protein in this formalin-fixed, paraffin-embedded tissue cohort. In addition, a quantitative approach was developed to more accurately assess the amount of HER-2/ neu protein identified by immunostaining tumor tissue. This was done using a purified HER-2/ neu protein synthesized in a bacterial expression vector and protein lysates derived from a series of cell lines, engineered to express a defined range of HER-2/ neu oncoprotein levels. By using cells with defined expression levels as calibration material, computerized image analysis of immunohistochemical staining could be used to determine the amount of oncoprotein product in these cell lines as well as in human breast cancer specimens. Quantitation of the amount of HER-2/ neu protein product determined by computerized image analysis of immunohistochemical assays correlated very closely with quantitative analysis of a series of molecularly characterized breast cancer cell lines and breast cancer tissue specimens. Breast cancer cells with no overexpression of HER-2/ neu had an average oncoprotein content of 0.18 ± 0.02 (SE) pg/cell, whereas the content of those with overexpression was as follows: 2.01 ± 0.73 pg/cell in cancers with overexpression but no amplification; 2.60 ± 0.47 pg/cell in cancers with 2 to 5-fold amplification and overexpression; and 3.38 ± 0.29 pg/cell in cancers with more than 5-fold amplification and overexpression. HER-2/ neu overexpression was identified in 41 of 105 relapsed cases and in 21 of 105 matched Disease-free controls. The risk of developing Recurrent Disease in node-negative women with any level of HER-2/ neu overexpression was 3.0 times that of women whose breast cancer lacked overexpression while the group of patients with high overexpression had a risk of recurrence 9.5 times greater than those whose breast cancers had normal expression ( P = 0.0001). Analysis of various subgroups showed significantly increased risks in pre- and postmenopausal women as well as in women with estrogen receptor-negative and small (T1A) breast cancers indicating the increased risk of recurrence extended across several subgroups of node-negative breast cancer patients. Our results demonstrate that HER-2/ neu overexpression is an independent indicator of increased risk of developing Recurrent Disease in women with node-negative breast cancer. Although frozen tissue is optimal for analysis, formalin-fixed, paraffin-embedded tissue can yield meaningful results when reagents of sufficient sensitivity and specificity are used. Finally, the quantitative amount of oncoprotein in tumor cells can be determined using immunohistochemistry in conjunction with computerized image analysis.

  • her 2 neu expression in node negative breast cancer direct tissue quantitation by computerized image analysis and association of overexpression with increased risk of Recurrent Disease
    Cancer Research, 1993
    Co-Authors: Michael F Press, Malcolm C Pike, Victoria R Chazin, Gene Hung, Judith A Udove, Mitchell Markowicz, John Danyluk, William Godolphin, Mark X Sliwkowski, Robert W Akita
    Abstract:

    The HER-2/neu proto-oncogene (also known as c-erb B-2) is homologous with, but distinct from, the epidermal growth factor receptor. Amplification of this gene in node-positive breast cancers has been shown to correlate with both earlier relapse and shorter overall survival. In node-negative breast cancer patients, the subgroup for which accurate prognostic data could make a significant contribution to treatment decisions, the prognostic utility of HER-2/neu amplification and/or overexpression has been controversial. The purpose of this report is to address the issues surrounding this controversy and to evaluate the prognostic utility of overexpression in a carefully followed group of patients using appropriately characterized reagents and methods. In this report we present data from a study of HER-2/neu expression designed specifically to test whether or not overexpression is associated with an increased risk of recurrence in node-negative breast cancers. From a cohort of 704 women with node-negative breast cancer who experienced Recurrent Disease (relapsed cases) 105 were matched with 105 women with no recurrence (Disease-free controls) after the equivalent follow-up period. Immunohistochemistry was used to assess HER-2/neu expression in archival tissue blocks from both relapsed cases and their matched Disease-free controls. Importantly, a series of molecularly characterized breast cancer specimens were used to confirm that the antibody used was of sufficient sensitivity and specificity to identify those cancers overexpressing the HER-2/neu protein in this formalin-fixed, paraffin-embedded tissue cohort. In addition, a quantitative approach was developed to more accurately assess the amount of HER-2/neu protein identified by immunostaining tumor tissue. This was done using a purified HER-2/neu protein synthesized in a bacterial expression vector and protein lysates derived from a series of cell lines, engineered to express a defined range of HER-2/neu oncoprotein levels. By using cells with defined expression levels as calibration material, computerized image analysis of immunohistochemical staining could be used to determine the amount of oncoprotein product in these cell lines as well as in human breast cancer specimens. Quantitation of the amount of HER-2/neu protein product determined by computerized image analysis of immunohistochemical assays correlated very closely with quantitative analysis of a series of molecularly characterized breast cancer cell lines and breast cancer tissue specimens.(ABSTRACT TRUNCATED AT 400 WORDS)

Michael F Press - One of the best experts on this subject based on the ideXlab platform.

  • her 2 neu expression in node negative breast cancer direct tissue quantitation by computerized image analysis and association of overexpression with increased risk of Recurrent Disease
    Cancer Research, 1993
    Co-Authors: Michael F Press, Malcolm C Pike, Victoria R Chazin, Gene Hung, Judith A Udove, Mitchell Markowicz, John Danyluk, William Godolphin, Mark X Sliwkowski, Robert W Akita
    Abstract:

    Abstract The HER-2/ neu proto-oncogene (also known as c- ceb B-2) is homologous with, but distinct from, the epidermal growth factor receptor. Amplification of this gene in node-positive breast cancers has been shown to correlate with both earlier relapse and shorter overall survival. In node-negative breast cancer patients, the subgroup for which accurate prognostic data could make a significant contribution to treatment decisions, the prognostic utility of HER-2/ neu amplification and/or overexpression has been controversial. The purpose of this report is to address the issues surrounding this controversy and to evaluate the prognostic utility of overexpression in a carefully followed group of patients using appropriately characterized reagents and methods. In this report we present data from a study of HER-2/ neu expression designed specifically to test whether or not overexpression is associated with an increased risk of recurrence in node-negative breast cancers. From a cohort of 704 women with node-negative breast cancer who experienced Recurrent Disease (relapsed cases) 105 were matched with 105 women with no recurrence (Disease-free controls) after the equivalent follow-up period. Immunohistochemistry was used to assess HER-2/ neu expression in archival tissue blocks from both relapsed cases and their matched Disease-free controls. Importantly, a series of molecularly characterized breast cancer specimens were used to confirm that the antibody used was of sufficient sensitivity and specificity to identify those cancers overexpressing the HER-2/ neu protein in this formalin-fixed, paraffin-embedded tissue cohort. In addition, a quantitative approach was developed to more accurately assess the amount of HER-2/ neu protein identified by immunostaining tumor tissue. This was done using a purified HER-2/ neu protein synthesized in a bacterial expression vector and protein lysates derived from a series of cell lines, engineered to express a defined range of HER-2/ neu oncoprotein levels. By using cells with defined expression levels as calibration material, computerized image analysis of immunohistochemical staining could be used to determine the amount of oncoprotein product in these cell lines as well as in human breast cancer specimens. Quantitation of the amount of HER-2/ neu protein product determined by computerized image analysis of immunohistochemical assays correlated very closely with quantitative analysis of a series of molecularly characterized breast cancer cell lines and breast cancer tissue specimens. Breast cancer cells with no overexpression of HER-2/ neu had an average oncoprotein content of 0.18 ± 0.02 (SE) pg/cell, whereas the content of those with overexpression was as follows: 2.01 ± 0.73 pg/cell in cancers with overexpression but no amplification; 2.60 ± 0.47 pg/cell in cancers with 2 to 5-fold amplification and overexpression; and 3.38 ± 0.29 pg/cell in cancers with more than 5-fold amplification and overexpression. HER-2/ neu overexpression was identified in 41 of 105 relapsed cases and in 21 of 105 matched Disease-free controls. The risk of developing Recurrent Disease in node-negative women with any level of HER-2/ neu overexpression was 3.0 times that of women whose breast cancer lacked overexpression while the group of patients with high overexpression had a risk of recurrence 9.5 times greater than those whose breast cancers had normal expression ( P = 0.0001). Analysis of various subgroups showed significantly increased risks in pre- and postmenopausal women as well as in women with estrogen receptor-negative and small (T1A) breast cancers indicating the increased risk of recurrence extended across several subgroups of node-negative breast cancer patients. Our results demonstrate that HER-2/ neu overexpression is an independent indicator of increased risk of developing Recurrent Disease in women with node-negative breast cancer. Although frozen tissue is optimal for analysis, formalin-fixed, paraffin-embedded tissue can yield meaningful results when reagents of sufficient sensitivity and specificity are used. Finally, the quantitative amount of oncoprotein in tumor cells can be determined using immunohistochemistry in conjunction with computerized image analysis.

  • her 2 neu expression in node negative breast cancer direct tissue quantitation by computerized image analysis and association of overexpression with increased risk of Recurrent Disease
    Cancer Research, 1993
    Co-Authors: Michael F Press, Malcolm C Pike, Victoria R Chazin, Gene Hung, Judith A Udove, Mitchell Markowicz, John Danyluk, William Godolphin, Mark X Sliwkowski, Robert W Akita
    Abstract:

    The HER-2/neu proto-oncogene (also known as c-erb B-2) is homologous with, but distinct from, the epidermal growth factor receptor. Amplification of this gene in node-positive breast cancers has been shown to correlate with both earlier relapse and shorter overall survival. In node-negative breast cancer patients, the subgroup for which accurate prognostic data could make a significant contribution to treatment decisions, the prognostic utility of HER-2/neu amplification and/or overexpression has been controversial. The purpose of this report is to address the issues surrounding this controversy and to evaluate the prognostic utility of overexpression in a carefully followed group of patients using appropriately characterized reagents and methods. In this report we present data from a study of HER-2/neu expression designed specifically to test whether or not overexpression is associated with an increased risk of recurrence in node-negative breast cancers. From a cohort of 704 women with node-negative breast cancer who experienced Recurrent Disease (relapsed cases) 105 were matched with 105 women with no recurrence (Disease-free controls) after the equivalent follow-up period. Immunohistochemistry was used to assess HER-2/neu expression in archival tissue blocks from both relapsed cases and their matched Disease-free controls. Importantly, a series of molecularly characterized breast cancer specimens were used to confirm that the antibody used was of sufficient sensitivity and specificity to identify those cancers overexpressing the HER-2/neu protein in this formalin-fixed, paraffin-embedded tissue cohort. In addition, a quantitative approach was developed to more accurately assess the amount of HER-2/neu protein identified by immunostaining tumor tissue. This was done using a purified HER-2/neu protein synthesized in a bacterial expression vector and protein lysates derived from a series of cell lines, engineered to express a defined range of HER-2/neu oncoprotein levels. By using cells with defined expression levels as calibration material, computerized image analysis of immunohistochemical staining could be used to determine the amount of oncoprotein product in these cell lines as well as in human breast cancer specimens. Quantitation of the amount of HER-2/neu protein product determined by computerized image analysis of immunohistochemical assays correlated very closely with quantitative analysis of a series of molecularly characterized breast cancer cell lines and breast cancer tissue specimens.(ABSTRACT TRUNCATED AT 400 WORDS)

Nicoletta Colombo - One of the best experts on this subject based on the ideXlab platform.

  • esmo esgo consensus conference recommendations on ovarian cancer pathology and molecular biology early and advanced stages borderline tumours and Recurrent Disease
    International Journal of Gynecological Cancer, 2019
    Co-Authors: Nicoletta Colombo, C Sessa, A Du Bois, J A Ledermann, W G Mccluggage, Iain A Mcneish, P Morice, S Pignata, I Raycoquard
    Abstract:

    The development of guidelines is one of the core activities of the European Society for Medical Oncology (ESMO) and European Society of Gynaecologial Oncology (ESGO), as part of the mission of both societies to improve the quality of care for patients with cancer across Europe. ESMO and ESGO jointly developed clinically relevant and evidence-based recommendations in several selected areas in order to improve the quality of care for women with ovarian cancer. The ESMO–ESGO consensus conference on ovarian cancer was held on April 12–14, 2018 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of ovarian cancer. Before the conference, the expert panel worked on five clinically relevant questions regarding ovarian cancer relating to each of the following four areas: pathology and molecular biology, early-stage and borderline tumours, advanced stage Disease and Recurrent Disease. Relevant scientific literature, as identified using a systematic search, was reviewed in advance. During the consensus conference, the panel developed recommendations for each specific question and a consensus was reached. The recommendations presented here are thus based on the best available evidence and expert agreement. This article presents the recommendations of this ESMO–ESGO consensus conference, together with a summary of evidence supporting each recommendation.

  • esmo esgo consensus conference recommendations on ovarian cancer pathology and molecular biology early and advanced stages borderline tumours and Recurrent Disease
    Annals of Oncology, 2019
    Co-Authors: Nicoletta Colombo, C Sessa, A Du Bois, J A Ledermann, W G Mccluggage, Iain A Mcneish, P Morice, S Pignata, I Raycoquard, I Vergote
    Abstract:

    The development of guidelines recommendations is one of the core activities of the European Society for Medical Oncology (ESMO) and European Society of Gynaecologial Oncology (ESGO), as part of the mission of both societies to improve the quality of care for patients with cancer across Europe. ESMO and ESGO jointly developed clinically relevant and evidence-based recommendations in several selected areas in order to improve the quality of care for women with ovarian cancer. The ESMO-ESGO consensus conference on ovarian cancer was held on 12-14 April 2018 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of ovarian cancer. Before the conference, the expert panel worked on five clinically relevant questions regarding ovarian cancer relating to each of the following four areas: pathology and molecular biology, early-stage and borderline tumours, advanced stage Disease and Recurrent Disease. Relevant scientific literature, as identified using a systematic search, was reviewed in advance. During the consensus conference, the panel developed recommendations for each specific question and a consensus was reached. The recommendations presented here are thus based on the best available evidence and expert agreement. This article presents the recommendations of this ESMO-ESGO consensus conference, together with a summary of evidence supporting each recommendation.

John Danyluk - One of the best experts on this subject based on the ideXlab platform.

  • her 2 neu expression in node negative breast cancer direct tissue quantitation by computerized image analysis and association of overexpression with increased risk of Recurrent Disease
    Cancer Research, 1993
    Co-Authors: Michael F Press, Malcolm C Pike, Victoria R Chazin, Gene Hung, Judith A Udove, Mitchell Markowicz, John Danyluk, William Godolphin, Mark X Sliwkowski, Robert W Akita
    Abstract:

    Abstract The HER-2/ neu proto-oncogene (also known as c- ceb B-2) is homologous with, but distinct from, the epidermal growth factor receptor. Amplification of this gene in node-positive breast cancers has been shown to correlate with both earlier relapse and shorter overall survival. In node-negative breast cancer patients, the subgroup for which accurate prognostic data could make a significant contribution to treatment decisions, the prognostic utility of HER-2/ neu amplification and/or overexpression has been controversial. The purpose of this report is to address the issues surrounding this controversy and to evaluate the prognostic utility of overexpression in a carefully followed group of patients using appropriately characterized reagents and methods. In this report we present data from a study of HER-2/ neu expression designed specifically to test whether or not overexpression is associated with an increased risk of recurrence in node-negative breast cancers. From a cohort of 704 women with node-negative breast cancer who experienced Recurrent Disease (relapsed cases) 105 were matched with 105 women with no recurrence (Disease-free controls) after the equivalent follow-up period. Immunohistochemistry was used to assess HER-2/ neu expression in archival tissue blocks from both relapsed cases and their matched Disease-free controls. Importantly, a series of molecularly characterized breast cancer specimens were used to confirm that the antibody used was of sufficient sensitivity and specificity to identify those cancers overexpressing the HER-2/ neu protein in this formalin-fixed, paraffin-embedded tissue cohort. In addition, a quantitative approach was developed to more accurately assess the amount of HER-2/ neu protein identified by immunostaining tumor tissue. This was done using a purified HER-2/ neu protein synthesized in a bacterial expression vector and protein lysates derived from a series of cell lines, engineered to express a defined range of HER-2/ neu oncoprotein levels. By using cells with defined expression levels as calibration material, computerized image analysis of immunohistochemical staining could be used to determine the amount of oncoprotein product in these cell lines as well as in human breast cancer specimens. Quantitation of the amount of HER-2/ neu protein product determined by computerized image analysis of immunohistochemical assays correlated very closely with quantitative analysis of a series of molecularly characterized breast cancer cell lines and breast cancer tissue specimens. Breast cancer cells with no overexpression of HER-2/ neu had an average oncoprotein content of 0.18 ± 0.02 (SE) pg/cell, whereas the content of those with overexpression was as follows: 2.01 ± 0.73 pg/cell in cancers with overexpression but no amplification; 2.60 ± 0.47 pg/cell in cancers with 2 to 5-fold amplification and overexpression; and 3.38 ± 0.29 pg/cell in cancers with more than 5-fold amplification and overexpression. HER-2/ neu overexpression was identified in 41 of 105 relapsed cases and in 21 of 105 matched Disease-free controls. The risk of developing Recurrent Disease in node-negative women with any level of HER-2/ neu overexpression was 3.0 times that of women whose breast cancer lacked overexpression while the group of patients with high overexpression had a risk of recurrence 9.5 times greater than those whose breast cancers had normal expression ( P = 0.0001). Analysis of various subgroups showed significantly increased risks in pre- and postmenopausal women as well as in women with estrogen receptor-negative and small (T1A) breast cancers indicating the increased risk of recurrence extended across several subgroups of node-negative breast cancer patients. Our results demonstrate that HER-2/ neu overexpression is an independent indicator of increased risk of developing Recurrent Disease in women with node-negative breast cancer. Although frozen tissue is optimal for analysis, formalin-fixed, paraffin-embedded tissue can yield meaningful results when reagents of sufficient sensitivity and specificity are used. Finally, the quantitative amount of oncoprotein in tumor cells can be determined using immunohistochemistry in conjunction with computerized image analysis.

  • her 2 neu expression in node negative breast cancer direct tissue quantitation by computerized image analysis and association of overexpression with increased risk of Recurrent Disease
    Cancer Research, 1993
    Co-Authors: Michael F Press, Malcolm C Pike, Victoria R Chazin, Gene Hung, Judith A Udove, Mitchell Markowicz, John Danyluk, William Godolphin, Mark X Sliwkowski, Robert W Akita
    Abstract:

    The HER-2/neu proto-oncogene (also known as c-erb B-2) is homologous with, but distinct from, the epidermal growth factor receptor. Amplification of this gene in node-positive breast cancers has been shown to correlate with both earlier relapse and shorter overall survival. In node-negative breast cancer patients, the subgroup for which accurate prognostic data could make a significant contribution to treatment decisions, the prognostic utility of HER-2/neu amplification and/or overexpression has been controversial. The purpose of this report is to address the issues surrounding this controversy and to evaluate the prognostic utility of overexpression in a carefully followed group of patients using appropriately characterized reagents and methods. In this report we present data from a study of HER-2/neu expression designed specifically to test whether or not overexpression is associated with an increased risk of recurrence in node-negative breast cancers. From a cohort of 704 women with node-negative breast cancer who experienced Recurrent Disease (relapsed cases) 105 were matched with 105 women with no recurrence (Disease-free controls) after the equivalent follow-up period. Immunohistochemistry was used to assess HER-2/neu expression in archival tissue blocks from both relapsed cases and their matched Disease-free controls. Importantly, a series of molecularly characterized breast cancer specimens were used to confirm that the antibody used was of sufficient sensitivity and specificity to identify those cancers overexpressing the HER-2/neu protein in this formalin-fixed, paraffin-embedded tissue cohort. In addition, a quantitative approach was developed to more accurately assess the amount of HER-2/neu protein identified by immunostaining tumor tissue. This was done using a purified HER-2/neu protein synthesized in a bacterial expression vector and protein lysates derived from a series of cell lines, engineered to express a defined range of HER-2/neu oncoprotein levels. By using cells with defined expression levels as calibration material, computerized image analysis of immunohistochemical staining could be used to determine the amount of oncoprotein product in these cell lines as well as in human breast cancer specimens. Quantitation of the amount of HER-2/neu protein product determined by computerized image analysis of immunohistochemical assays correlated very closely with quantitative analysis of a series of molecularly characterized breast cancer cell lines and breast cancer tissue specimens.(ABSTRACT TRUNCATED AT 400 WORDS)

Mark X Sliwkowski - One of the best experts on this subject based on the ideXlab platform.

  • her 2 neu expression in node negative breast cancer direct tissue quantitation by computerized image analysis and association of overexpression with increased risk of Recurrent Disease
    Cancer Research, 1993
    Co-Authors: Michael F Press, Malcolm C Pike, Victoria R Chazin, Gene Hung, Judith A Udove, Mitchell Markowicz, John Danyluk, William Godolphin, Mark X Sliwkowski, Robert W Akita
    Abstract:

    Abstract The HER-2/ neu proto-oncogene (also known as c- ceb B-2) is homologous with, but distinct from, the epidermal growth factor receptor. Amplification of this gene in node-positive breast cancers has been shown to correlate with both earlier relapse and shorter overall survival. In node-negative breast cancer patients, the subgroup for which accurate prognostic data could make a significant contribution to treatment decisions, the prognostic utility of HER-2/ neu amplification and/or overexpression has been controversial. The purpose of this report is to address the issues surrounding this controversy and to evaluate the prognostic utility of overexpression in a carefully followed group of patients using appropriately characterized reagents and methods. In this report we present data from a study of HER-2/ neu expression designed specifically to test whether or not overexpression is associated with an increased risk of recurrence in node-negative breast cancers. From a cohort of 704 women with node-negative breast cancer who experienced Recurrent Disease (relapsed cases) 105 were matched with 105 women with no recurrence (Disease-free controls) after the equivalent follow-up period. Immunohistochemistry was used to assess HER-2/ neu expression in archival tissue blocks from both relapsed cases and their matched Disease-free controls. Importantly, a series of molecularly characterized breast cancer specimens were used to confirm that the antibody used was of sufficient sensitivity and specificity to identify those cancers overexpressing the HER-2/ neu protein in this formalin-fixed, paraffin-embedded tissue cohort. In addition, a quantitative approach was developed to more accurately assess the amount of HER-2/ neu protein identified by immunostaining tumor tissue. This was done using a purified HER-2/ neu protein synthesized in a bacterial expression vector and protein lysates derived from a series of cell lines, engineered to express a defined range of HER-2/ neu oncoprotein levels. By using cells with defined expression levels as calibration material, computerized image analysis of immunohistochemical staining could be used to determine the amount of oncoprotein product in these cell lines as well as in human breast cancer specimens. Quantitation of the amount of HER-2/ neu protein product determined by computerized image analysis of immunohistochemical assays correlated very closely with quantitative analysis of a series of molecularly characterized breast cancer cell lines and breast cancer tissue specimens. Breast cancer cells with no overexpression of HER-2/ neu had an average oncoprotein content of 0.18 ± 0.02 (SE) pg/cell, whereas the content of those with overexpression was as follows: 2.01 ± 0.73 pg/cell in cancers with overexpression but no amplification; 2.60 ± 0.47 pg/cell in cancers with 2 to 5-fold amplification and overexpression; and 3.38 ± 0.29 pg/cell in cancers with more than 5-fold amplification and overexpression. HER-2/ neu overexpression was identified in 41 of 105 relapsed cases and in 21 of 105 matched Disease-free controls. The risk of developing Recurrent Disease in node-negative women with any level of HER-2/ neu overexpression was 3.0 times that of women whose breast cancer lacked overexpression while the group of patients with high overexpression had a risk of recurrence 9.5 times greater than those whose breast cancers had normal expression ( P = 0.0001). Analysis of various subgroups showed significantly increased risks in pre- and postmenopausal women as well as in women with estrogen receptor-negative and small (T1A) breast cancers indicating the increased risk of recurrence extended across several subgroups of node-negative breast cancer patients. Our results demonstrate that HER-2/ neu overexpression is an independent indicator of increased risk of developing Recurrent Disease in women with node-negative breast cancer. Although frozen tissue is optimal for analysis, formalin-fixed, paraffin-embedded tissue can yield meaningful results when reagents of sufficient sensitivity and specificity are used. Finally, the quantitative amount of oncoprotein in tumor cells can be determined using immunohistochemistry in conjunction with computerized image analysis.

  • her 2 neu expression in node negative breast cancer direct tissue quantitation by computerized image analysis and association of overexpression with increased risk of Recurrent Disease
    Cancer Research, 1993
    Co-Authors: Michael F Press, Malcolm C Pike, Victoria R Chazin, Gene Hung, Judith A Udove, Mitchell Markowicz, John Danyluk, William Godolphin, Mark X Sliwkowski, Robert W Akita
    Abstract:

    The HER-2/neu proto-oncogene (also known as c-erb B-2) is homologous with, but distinct from, the epidermal growth factor receptor. Amplification of this gene in node-positive breast cancers has been shown to correlate with both earlier relapse and shorter overall survival. In node-negative breast cancer patients, the subgroup for which accurate prognostic data could make a significant contribution to treatment decisions, the prognostic utility of HER-2/neu amplification and/or overexpression has been controversial. The purpose of this report is to address the issues surrounding this controversy and to evaluate the prognostic utility of overexpression in a carefully followed group of patients using appropriately characterized reagents and methods. In this report we present data from a study of HER-2/neu expression designed specifically to test whether or not overexpression is associated with an increased risk of recurrence in node-negative breast cancers. From a cohort of 704 women with node-negative breast cancer who experienced Recurrent Disease (relapsed cases) 105 were matched with 105 women with no recurrence (Disease-free controls) after the equivalent follow-up period. Immunohistochemistry was used to assess HER-2/neu expression in archival tissue blocks from both relapsed cases and their matched Disease-free controls. Importantly, a series of molecularly characterized breast cancer specimens were used to confirm that the antibody used was of sufficient sensitivity and specificity to identify those cancers overexpressing the HER-2/neu protein in this formalin-fixed, paraffin-embedded tissue cohort. In addition, a quantitative approach was developed to more accurately assess the amount of HER-2/neu protein identified by immunostaining tumor tissue. This was done using a purified HER-2/neu protein synthesized in a bacterial expression vector and protein lysates derived from a series of cell lines, engineered to express a defined range of HER-2/neu oncoprotein levels. By using cells with defined expression levels as calibration material, computerized image analysis of immunohistochemical staining could be used to determine the amount of oncoprotein product in these cell lines as well as in human breast cancer specimens. Quantitation of the amount of HER-2/neu protein product determined by computerized image analysis of immunohistochemical assays correlated very closely with quantitative analysis of a series of molecularly characterized breast cancer cell lines and breast cancer tissue specimens.(ABSTRACT TRUNCATED AT 400 WORDS)