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1. Association of p16 expression with prognosis varies across ovarian carcinoma histotypes: an Ovarian Tumor Tissue Analysis consortium study.

Author

Rambau, Peter F, Vierkant, Robert A, Intermaggio, Maria P, Kelemen, Linda E, Goodman, Marc T, Herpel, Esther, Pharoah, Paul D, Kommoss, Stefan, Jimenez-Linan, Mercedes, Karlan, Beth Y, Gentry-Maharaj, Aleksandra, Menon, Usha, Polo, Susanna Hernando, Candido Dos Reis, Francisco J, Doherty, Jennifer Anne, Gayther, Simon A, Sharma, Raghwa, Larson, Melissa C, Harnett, Paul R, Hatfield, Emma, de Andrade, Jurandyr M, Nelson, Gregg S, Steed, Helen, Schildkraut, Joellen M, Carney, Micheal E, Høgdall, Estrid, Whittemore, Alice S, Widschwendter, Martin, Kennedy, Catherine J, Wang, Frances, Wang, Qin, Wang, Chen, Armasu, Sebastian M, Daley, Frances, Coulson, Penny, Jones, Micheal E, Anglesio, Micheal S, Chow, Christine, de Fazio, Anna, García-Closas, Montserrat, Brucker, Sara Y, Cybulski, Cezary, Harris, Holly R, Hartkopf, Andreas D, Huzarski, Tomasz, Jensen, Allan, Lubiński, Jan, Oszurek, Oleg, Benitez, Javier, Mina, Fady, Staebler, Annette, Taran, Florin Andrei, Pasternak, Jana, Talhouk, Aline, Rossing, Mary Anne, Hendley, Joy, AOCS Group, Edwards, Robert P, Fereday, Sian, Modugno, Francesmary, Ness, Roberta B, Sieh, Weiva, El-Bahrawy, Mona A, Winham, Stacey J, Lester, Jenny, Kjaer, Susanne K, Gronwald, Jacek, Sinn, Peter, Fasching, Peter A, Chang-Claude, Jenny, Moysich, Kirsten B, Bowtell, David D, Hernandez, Brenda Y, Luk, Hugh, Behrens, Sabine, Shah, Mitul, Jung, Audrey, Ghatage, Prafull, Alsop, Jennifer, Alsop, Kathryn, García-Donas, Jesús, Thompson, Pamela J, Swerdlow, Anthony J, Karpinskyj, Chloe, Cazorla-Jiménez, Alicia, García, María J, Deen, Susha, Wilkens, Lynne R, Palacios, José, Berchuck, Andrew, Koziak, Jennifer M, Brenton, James D, Cook, Linda S, Goode, Ellen L, Huntsman, David G, Ramus, Susan J, and Köbel, Martin

Subjects
AOCS Group, Ovary, Humans, Adenocarcinoma, Mucinous, Cystadenocarcinoma, Serous, Ovarian Neoplasms, Prognosis, Immunohistochemistry, Survival Rate, Adult, Aged, Middle Aged, Female, Cyclin-Dependent Kinase Inhibitor p16, RT-QPCR, immunocytochemistry, ovary, Adenocarcinoma, Mucinous, Cystadenocarcinoma, Serous, Cancer, Genetics, Ovarian Cancer, Rare Diseases, 2.1 Biological and endogenous factors
Abstract

We aimed to validate the prognostic association of p16 expression in ovarian high-grade serous carcinomas (HGSC) and to explore it in other ovarian carcinoma histotypes. p16 protein expression was assessed by clinical-grade immunohistochemistry in 6525 ovarian carcinomas including 4334 HGSC using tissue microarrays from 24 studies participating in the Ovarian Tumor Tissue Analysis consortium. p16 expression patterns were interpreted as abnormal (either overexpression referred to as block expression or absence) or normal (heterogeneous). CDKN2A (which encodes p16) mRNA expression was also analyzed in a subset (n = 2280) mostly representing HGSC (n = 2010). Association of p16 expression with overall survival (OS) was determined within histotypes as was CDKN2A expression for HGSC only. p16 block expression was most frequent in HGSC (56%) but neither protein nor mRNA expression was associated with OS. However, relative to heterogeneous expression, block expression was associated with shorter OS in endometriosis-associated carcinomas, clear cell [hazard ratio (HR): 2.02, 95% confidence (CI) 1.47-2.77, p < 0.001] and endometrioid (HR: 1.88, 95% CI 1.30-2.75, p = 0.004), while absence was associated with shorter OS in low-grade serous carcinomas (HR: 2.95, 95% CI 1.61-5.38, p = 0.001). Absence was most frequent in mucinous carcinoma (50%), and was not associated with OS in this histotype. The prognostic value of p16 expression is histotype-specific and pattern dependent. We provide definitive evidence against an association of p16 expression with survival in ovarian HGSC as previously suggested. Block expression of p16 in clear cell and endometrioid carcinoma should be further validated as a prognostic marker, and absence in low-grade serous carcinoma justifies CDK4 inhibition.

Published
2018

3. A combination of the immunohistochemical markers CK7 and SATB2 is highly sensitive and specific for distinguishing primary ovarian mucinous tumors from colorectal and appendiceal metastases

Author

Meagher, Nicola S., Wang, Linyuan, Rambau, Peter F., Intermaggio, Maria P., Huntsman, David G., Wilkens, Lynne R., El-Bahrawy, Mona A., Ness, Roberta B., Odunsi, Kunle, Steed, Helen, Herpel, Esther, Anglesio, Michael S., Zhang, Bonnie, Lambie, Neil, Swerdlow, Anthony J., Lubiński, Jan, Vierkant, Robert A., Goode, Ellen L., Menon, Usha, Toloczko-Grabarek, Aleksandra, Oszurek, Oleg, Bilic, Sanela, Talhouk, Aline, García-Closas, Montserrat, Wang, Qin, Tan, Adeline, Farrell, Rhonda, Kennedy, Catherine J., Jimenez-Linan, Mercedes, Sundfeldt, Karin, Etter, John L., Menkiszak, Janusz, Goodman, Marc T., Klonowski, Paul, Leung, Yee, Winham, Stacey J., Moysich, Kirsten B., Behrens, Sabine, Kluz, Tomasz, Edwards, Robert P., Gronwald, Jacek, Modugno, Francesmary, Hernandez, Brenda Y, Chow, Christine, Kelemen, Linda E., Keeney, Gary L., Carney, Michael E., Natanzon, Yanina, Robertson, Gregory, Sharma, Raghwa, Gayther, Simon A., Alsop, Jennifer, Luk, Hugh, Karpinskyj, Chloe, Campbell, Ian, Sinn, Peter, Gentry-Maharaj, Aleksandra, Coulson, Penny, Chang-Claude, Jenny, Shah, Mitul, Widschwendter, Martin, Tang, Katrina, Schoemaker, Minouk J., Koziak, Jennifer M., Cook, Linda S., Brenton, James D., Daley, Frances, Kristjansdottir, Björg, Mateoiu, Constantina, Larson, Melissa C., Harnett, Paul R., Jung, Audrey, deFazio, Anna, Gorringe, Kylie L., Pharoah, Paul D.P., Minoo, Parham, Stewart, Colin, Bathe, Oliver F., Gui, Xianyong, Cohen, Paul, Ramus, Susan J., and Köbel, Martin

Published
2019
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5. Homologous recombination DNA repair deficiency and PARP inhibition activity in primary triple negative breast cancer

Author

Chopra, Neha, Tovey, Holly, Pearson, Alex, Cutts, Ros, Toms, Christy, Proszek, Paula, Hubank, Michael, Dowsett, Mitch, Dodson, Andrew, Daley, Frances, Kriplani, Divya, Gevensleben, Heidi, Davies, Helen Ruth, Degasperi, Andrea, Roylance, Rebecca, Chan, Stephen, Tutt, Andrew, Skene, Anthony, Evans, Abigail, Bliss, Judith M., Nik-Zainal, Serena, and Turner, Nicholas C.

Published
2020
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6. Supplementary Table Descriptions from Evaluation of CDK12 Protein Expression as a Potential Novel Biomarker for DNA Damage Response–Targeted Therapies in Breast Cancer

Author

Naidoo, Kalnisha, primary, Wai, Patty T., primary, Maguire, Sarah L., primary, Daley, Frances, primary, Haider, Syed, primary, Kriplani, Divya, primary, Campbell, James, primary, Mirza, Hasan, primary, Grigoriadis, Anita, primary, Tutt, Andrew, primary, Moseley, Paul M., primary, Abdel-Fatah, Tarek M.A., primary, Chan, Stephen Y.T., primary, Madhusudan, Srinivasan, primary, Rhaka, Emad A., primary, Ellis, Ian O., primary, Lord, Christopher J., primary, Yuan, Yinyin, primary, Green, Andrew R., primary, and Natrajan, Rachael, primary

Published
2023
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7. Data from Evaluation of CDK12 Protein Expression as a Potential Novel Biomarker for DNA Damage Response–Targeted Therapies in Breast Cancer

Author

Naidoo, Kalnisha, primary, Wai, Patty T., primary, Maguire, Sarah L., primary, Daley, Frances, primary, Haider, Syed, primary, Kriplani, Divya, primary, Campbell, James, primary, Mirza, Hasan, primary, Grigoriadis, Anita, primary, Tutt, Andrew, primary, Moseley, Paul M., primary, Abdel-Fatah, Tarek M.A., primary, Chan, Stephen Y.T., primary, Madhusudan, Srinivasan, primary, Rhaka, Emad A., primary, Ellis, Ian O., primary, Lord, Christopher J., primary, Yuan, Yinyin, primary, Green, Andrew R., primary, and Natrajan, Rachael, primary

Published
2023
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8. Supplementary Tables S1-S10 from Evaluation of CDK12 Protein Expression as a Potential Novel Biomarker for DNA Damage Response–Targeted Therapies in Breast Cancer

Author

Naidoo, Kalnisha, primary, Wai, Patty T., primary, Maguire, Sarah L., primary, Daley, Frances, primary, Haider, Syed, primary, Kriplani, Divya, primary, Campbell, James, primary, Mirza, Hasan, primary, Grigoriadis, Anita, primary, Tutt, Andrew, primary, Moseley, Paul M., primary, Abdel-Fatah, Tarek M.A., primary, Chan, Stephen Y.T., primary, Madhusudan, Srinivasan, primary, Rhaka, Emad A., primary, Ellis, Ian O., primary, Lord, Christopher J., primary, Yuan, Yinyin, primary, Green, Andrew R., primary, and Natrajan, Rachael, primary

Published
2023
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9. Table S4 from 3D Functional Genomics Screens Identify CREBBP as a Targetable Driver in Aggressive Triple-Negative Breast Cancer

Author

Peck, Barrie, primary, Bland, Philip, primary, Mavrommati, Ioanna, primary, Muirhead, Gareth, primary, Cottom, Hannah, primary, Wai, Patty T., primary, Maguire, Sarah L., primary, Barker, Holly E., primary, Morrison, Eamonn, primary, Kriplani, Divya, primary, Yu, Lu, primary, Gibson, Amy, primary, Falgari, Giulia, primary, Brennan, Keith, primary, Farnie, Gillian, primary, Buus, Richard, primary, Marlow, Rebecca, primary, Novo, Daniela, primary, Knight, Eleanor, primary, Guppy, Naomi, primary, Kolarevic, Daniela, primary, Susnjar, Snezana, primary, Milijic, Natasa Medic, primary, Naidoo, Kalnisha, primary, Gazinska, Patrycja, primary, Roxanis, Ioannis, primary, Pancholi, Sunil, primary, Martin, Lesley-Ann, primary, Holgersen, Erle M., primary, Cheang, Maggie C.U., primary, Noor, Farzana, primary, Postel-Vinay, Sophie, primary, Quinn, Gerard, primary, McDade, Simon, primary, Krasny, Lukas, primary, Huang, Paul, primary, Daley, Frances, primary, Wallberg, Fredrik, primary, Choudhary, Jyoti S., primary, Haider, Syed, primary, Tutt, Andrew N., primary, and Natrajan, Rachael, primary

Published
2023
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11. Data from 3D Functional Genomics Screens Identify CREBBP as a Targetable Driver in Aggressive Triple-Negative Breast Cancer

Author

Peck, Barrie, primary, Bland, Philip, primary, Mavrommati, Ioanna, primary, Muirhead, Gareth, primary, Cottom, Hannah, primary, Wai, Patty T., primary, Maguire, Sarah L., primary, Barker, Holly E., primary, Morrison, Eamonn, primary, Kriplani, Divya, primary, Yu, Lu, primary, Gibson, Amy, primary, Falgari, Giulia, primary, Brennan, Keith, primary, Farnie, Gillian, primary, Buus, Richard, primary, Marlow, Rebecca, primary, Novo, Daniela, primary, Knight, Eleanor, primary, Guppy, Naomi, primary, Kolarevic, Daniela, primary, Susnjar, Snezana, primary, Milijic, Natasa Medic, primary, Naidoo, Kalnisha, primary, Gazinska, Patrycja, primary, Roxanis, Ioannis, primary, Pancholi, Sunil, primary, Martin, Lesley-Ann, primary, Holgersen, Erle M., primary, Cheang, Maggie C.U., primary, Noor, Farzana, primary, Postel-Vinay, Sophie, primary, Quinn, Gerard, primary, McDade, Simon, primary, Krasny, Lukas, primary, Huang, Paul, primary, Daley, Frances, primary, Wallberg, Fredrik, primary, Choudhary, Jyoti S., primary, Haider, Syed, primary, Tutt, Andrew N., primary, and Natrajan, Rachael, primary

Published
2023
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12. Supplementary Methods from 3D Functional Genomics Screens Identify CREBBP as a Targetable Driver in Aggressive Triple-Negative Breast Cancer

Author

Peck, Barrie, primary, Bland, Philip, primary, Mavrommati, Ioanna, primary, Muirhead, Gareth, primary, Cottom, Hannah, primary, Wai, Patty T., primary, Maguire, Sarah L., primary, Barker, Holly E., primary, Morrison, Eamonn, primary, Kriplani, Divya, primary, Yu, Lu, primary, Gibson, Amy, primary, Falgari, Giulia, primary, Brennan, Keith, primary, Farnie, Gillian, primary, Buus, Richard, primary, Marlow, Rebecca, primary, Novo, Daniela, primary, Knight, Eleanor, primary, Guppy, Naomi, primary, Kolarevic, Daniela, primary, Susnjar, Snezana, primary, Milijic, Natasa Medic, primary, Naidoo, Kalnisha, primary, Gazinska, Patrycja, primary, Roxanis, Ioannis, primary, Pancholi, Sunil, primary, Martin, Lesley-Ann, primary, Holgersen, Erle M., primary, Cheang, Maggie C.U., primary, Noor, Farzana, primary, Postel-Vinay, Sophie, primary, Quinn, Gerard, primary, McDade, Simon, primary, Krasny, Lukas, primary, Huang, Paul, primary, Daley, Frances, primary, Wallberg, Fredrik, primary, Choudhary, Jyoti S., primary, Haider, Syed, primary, Tutt, Andrew N., primary, and Natrajan, Rachael, primary

Published
2023
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13. Figure S1- S8 from 3D Functional Genomics Screens Identify CREBBP as a Targetable Driver in Aggressive Triple-Negative Breast Cancer

Author

Peck, Barrie, primary, Bland, Philip, primary, Mavrommati, Ioanna, primary, Muirhead, Gareth, primary, Cottom, Hannah, primary, Wai, Patty T., primary, Maguire, Sarah L., primary, Barker, Holly E., primary, Morrison, Eamonn, primary, Kriplani, Divya, primary, Yu, Lu, primary, Gibson, Amy, primary, Falgari, Giulia, primary, Brennan, Keith, primary, Farnie, Gillian, primary, Buus, Richard, primary, Marlow, Rebecca, primary, Novo, Daniela, primary, Knight, Eleanor, primary, Guppy, Naomi, primary, Kolarevic, Daniela, primary, Susnjar, Snezana, primary, Milijic, Natasa Medic, primary, Naidoo, Kalnisha, primary, Gazinska, Patrycja, primary, Roxanis, Ioannis, primary, Pancholi, Sunil, primary, Martin, Lesley-Ann, primary, Holgersen, Erle M., primary, Cheang, Maggie C.U., primary, Noor, Farzana, primary, Postel-Vinay, Sophie, primary, Quinn, Gerard, primary, McDade, Simon, primary, Krasny, Lukas, primary, Huang, Paul, primary, Daley, Frances, primary, Wallberg, Fredrik, primary, Choudhary, Jyoti S., primary, Haider, Syed, primary, Tutt, Andrew N., primary, and Natrajan, Rachael, primary

Published
2023
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16. Multi-candidate immunohistochemical markers to assess radiation response and prognosis in prostate cancer: results from the CHHiP trial of radiotherapy fractionation

Author

Wilkins, Anna, primary, Gusterson, Barry, additional, Tovey, Holly, additional, Griffin, Clare, additional, Stuttle, Christine, additional, Daley, Frances, additional, Corbishley, Catherine M., additional, Dearnaley, David, additional, Hall, Emma, additional, and Somaiah, Navita, additional

Published
2023
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17. Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases

Author

Frentzas, Sophia, Simoneau, Eve, Bridgeman, Victoria L, Vermeulen, Peter B, Foo, Shane, Kostaras, Eleftherios, Nathan, Mark R, Wotherspoon, Andrew, Gao, Zu-hua, Shi, Yu, Van den Eynden, Gert, Daley, Frances, Peckitt, Clare, Tan, Xianming, Salman, Ayat, Lazaris, Anthoula, Gazinska, Patrycja, Berg, Tracy J, Eltahir, Zak, Ritsma, Laila, van Rheenen, Jacco, Khashper, Alla, Brown, Gina, Nyström, Hanna, Sund, Malin, Van Laere, Steven, Loyer, Evelyne, Dirix, Luc, Cunningham, David, Metrakos, Peter, and Reynolds, Andrew R

Subjects
Angiogenesis inhibitors -- Patient outcomes, Liver cancer -- Drug therapy, Cancer metastasis -- Drug therapy, Biological sciences, Health
Abstract

The efficacy of angiogenesis inhibitors in cancer is limited by resistance mechanisms that are poorly understood. Notably, instead of through the induction of angiogenesis, tumor vascularization can occur through the nonangiogenic mechanism of vessel co-option. Here we show that vessel co-option is associated with a poor response to the anti-angiogenic agent bevacizumab in patients with colorectal cancer liver metastases. Moreover, we find that vessel co-option is also prevalent in human breast cancer liver metastases, a setting in which results with anti-angiogenic therapy have been disappointing. In preclinical mechanistic studies, we found that cancer cell motility mediated by the actin-related protein 2/3 complex (Arp2/3) is required for vessel co-option in liver metastases in vivo and that, in this setting, combined inhibition of angiogenesis and vessel co-option is more effective than the inhibition of angiogenesis alone. Vessel co-option is therefore a clinically relevant mechanism of resistance to anti-angiogenic therapy and combined inhibition of angiogenesis and vessel co-option might be a warranted therapeutic strategy., Author(s): Sophia Frentzas [1, 2]; Eve Simoneau [3]; Victoria L Bridgeman [1]; Peter B Vermeulen [1, 4]; Shane Foo [1]; Eleftherios Kostaras [1]; Mark R Nathan [1]; Andrew Wotherspoon [2]; [...]

Published
2016
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18. Vessel co‐option is common in human lung metastases and mediates resistance to anti‐angiogenic therapy in preclinical lung metastasis models

Author

Bridgeman, Victoria L, Vermeulen, Peter B, Foo, Shane, Bilecz, Agnes, Daley, Frances, Kostaras, Eleftherios, Nathan, Mark R, Wan, Elaine, Frentzas, Sophia, Schweiger, Thomas, Hegedus, Balazs, Hoetzenecker, Konrad, Renyi‐Vamos, Ferenc, Kuczynski, Elizabeth A, Vasudev, Naveen S, Larkin, James, Gore, Martin, Dvorak, Harold F, Paku, Sandor, Kerbel, Robert S, Dome, Balazs, and Reynolds, Andrew R

Published
2017
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20. Optimised ARID1A immunohistochemistry is an accurate predictor of ARID1A mutational status in gynaecological cancers

Author

Khalique, Saira, Naidoo, Kalnisha, Attygalle, Ayoma D, Kriplani, Divya, Daley, Frances, Lowe, Anne, Campbell, James, Jones, Thomas, Hubank, Michael, Fenwick, Kerry, Matthews, Nicholas, Rust, Alistair G, Lord, Christopher J, Banerjee, Susana, and Natrajan, Rachael

Subjects
next generation sequencing, clear cell ovarian cancer, Genital Neoplasms, Female, Nuclear Proteins, Biomarker, Original Articles, ARID1A immunohistochemistry, Immunohistochemistry, DNA-Binding Proteins, Next generation sequencing, Mutation, biomarker, Humans, Clear cell ovarian cancer, Original Article, Female, Transcription Factors
Abstract

ARID1A is a tumour suppressor gene that is frequently mutated in clear cell and endometrioid carcinomas of the ovary and endometrium and is an important clinical biomarker for novel treatment approaches for patients with ARID1A defects. However, the accuracy of ARID1A immunohistochemistry (IHC) as a surrogate for mutation status has not fully been established for patient stratification in clinical trials. Here we tested whether ARID1A IHC could reliably predict ARID1A mutations identified by next‐generation sequencing. Three commercially available antibodies – EPR13501 (Abcam), D2A8U (Cell Signaling), and HPA005456 (Sigma) – were optimised for IHC using cell line models and human tissue, and screened across a cohort of 45 gynaecological tumours. IHC was scored independently by three pathologists using an immunoreactive score. ARID1A mutation status was assessed using two independent sequencing platforms and the concordance between ARID1A mutation and protein expression was evaluated using Receiver Operating Characteristic statistics. Overall, 21 ARID1A mutations were identified in 14/43 assessable tumours (33%), the majority of which were predicted to be deleterious. Mutations were identified in 6/17 (35%) ovarian clear cell carcinomas, 5/8 (63%) ovarian endometrioid carcinomas, 2/5 (40%) endometrial carcinomas, and 1/7 (14%) carcinosarcomas. ROC analysis identified greater than 95% concordance between mutation status and IHC using a modified immunoreactive score for all three antibodies allowing a definitive cut‐point for ARID1A mutant status to be calculated. Comprehensive assessment of concordance of ARID1A IHC and mutation status identified EPR13501 as an optimal antibody, with 100% concordance between ARID1A mutation status and protein expression, across different gynaecological histological subtypes. It delivered the best inter‐rater agreement between all pathologists, as well as a clear cost‐benefit advantage. This could allow patients to be accurately stratified based on their ARID1A IHC status into early phase clinical trials. Gynaecological Cancer Fund The Royal Marsden Cancer Charity Breast Cancer Now . Grant Numbers: PRJNA432413 , PRJNA432343 Cancer Research UK The Monument Trust NHS NIHR Royal Marsden Hospital Biomedical Research Centre NCBI Sequence Read Archive

Published
2018

21. FFPE breast tumour blocks provide reliable sources of both germline and malignant DNA for investigation of genetic determinants of individual tumour responses to treatment

Author

Wilkins, Anna, Chauhan, Ritika, Rust, Alistair, Pearson, Alex, Daley, Frances, Manodoro, Floriana, Fenwick, Kerry, Bliss, Judith, Yarnold, John, and Somaiah, Navita

Subjects
Germline determinants, DNA Copy Number Variations, Gene Expression Profiling, Whole exome sequencing, High-Throughput Nucleotide Sequencing, Reproducibility of Results, Breast Neoplasms, DNA, Neoplasm, Clinical Trial, Combined Modality Therapy, Breast cancer, Germ Cells, Treatment Outcome, Humans, Exome, Female, Genetic Predisposition to Disease, Genetic Testing, Archival formalin fixed paraffin embedded tissue
Abstract

Background Bio-banked formalin-fixed paraffin-embedded (FFPE) tissues provide an excellent opportunity for translational genomic research. Historically matched blood has not always been collected as a source of germline DNA. This project aimed to establish if normal FFPE breast tissue could be used as an alternative to blood. Methods Exome sequencing was carried out on matched tumour tissue, normal breast tissue and blood on five patients in the START trial. Retrieved samples had been archived at different centres for at least 13 years. Following tissue macro-dissection and DNA extraction, targeted exome capture was performed using SureSelect Human All Exome v5 reagents (Agilent). Illumina paired-end libraries were prepared from the captured target regions and sequenced on a HiSeq2500 (Illumina) acquiring 2 × 75 bp reads. Somatic variants were called using the MuTect software analysis tool and copy number abnormalities (CNA) were identified using CNVkit. Targeted sequencing and droplet digital PCR were used to validate somatic variants and CNA, respectively. Results Overlap of somatic variants and CNA called on tumour versus blood and tumour versus normal breast tissue was good. Agreement in somatic variant calling ranged from 76.9 to 93.6%. Variants with an allele frequency lower than 10% were more difficult to validate irrespective of the type of germline DNA used. Pearson’s correlation coefficients for paired comparisons of CNA using blood or normal tissue as reference ranged from 0.70 to 0.94. Conclusions There is good correlation between the somatic mutations and CNA called using archived blood or normal breast tissue as germline reference material. Electronic supplementary material The online version of this article (10.1007/s10549-018-4798-7) contains supplementary material, which is available to authorised users.

Published
2018

22. 3D Functional Genomics Screens Identify CREBBP as a Targetable Driver in Aggressive Triple-Negative Breast Cancer

Author

Peck, Barrie, primary, Bland, Philip, additional, Mavrommati, Ioanna, additional, Muirhead, Gareth, additional, Cottom, Hannah, additional, Wai, Patty T., additional, Maguire, Sarah L., additional, Barker, Holly E., additional, Morrison, Eamonn, additional, Kriplani, Divya, additional, Yu, Lu, additional, Gibson, Amy, additional, Falgari, Giulia, additional, Brennan, Keith, additional, Farnie, Gillian, additional, Buus, Richard, additional, Marlow, Rebecca, additional, Novo, Daniela, additional, Knight, Eleanor, additional, Guppy, Naomi, additional, Kolarevic, Daniela, additional, Susnjar, Snezana, additional, Milijic, Natasa Medic, additional, Naidoo, Kalnisha, additional, Gazinska, Patrycja, additional, Roxanis, Ioannis, additional, Pancholi, Sunil, additional, Martin, Lesley-Ann, additional, Holgersen, Erle M., additional, Cheang, Maggie C.U., additional, Noor, Farzana, additional, Postel-Vinay, Sophie, additional, Quinn, Gerard, additional, McDade, Simon, additional, Krasny, Lukas, additional, Huang, Paul, additional, Daley, Frances, additional, Wallberg, Fredrik, additional, Choudhary, Jyoti S., additional, Haider, Syed, additional, Tutt, Andrew N., additional, and Natrajan, Rachael, additional

Published
2021
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24. SOX11 promotes invasive growth and ductal carcinoma in situ progression

Author

Oliemuller, Erik, Kogata, Naoko, Bland, Philip, Kriplani, Divya, Daley, Frances, Haider, Syed, Shah, Vandna, Sawyer, Elinor J, and Howard, Beatrice A

Subjects
Original Paper, DCIS, Stem Cells, Carcinoma, Ductal, Breast, Breast Neoplasms, Epithelial Cells, Mice, SCID, Aldehyde Dehydrogenase, invasion, Original Papers, SOXC Transcription Factors, Up-Regulation, embryonic mammary marker, mammary progenitor/stem cells, Mammary Glands, Animal, SOX11, Disease Progression, Animals, Humans, Female, skin and connective tissue diseases, ALDH1A1
Abstract

Here, we show that SOX11, an embryonic mammary marker that is normally silent in postnatal breast cells, is expressed in many oestrogen receptor‐negative preinvasive ductal carcinoma in situ (DCIS) lesions. Mature mammary epithelial cells engineered to express SOX11 showed alterations in progenitor cell populations, including an expanded basal‐like population with increased aldehyde dehydrogenase (ALDH) activity, and increased mammosphere‐forming capacity. DCIS.com cells engineered to express SOX11 showed increased ALDH activity, which is a feature of cancer stem cells. The CD44+/CD24–/ALDH+ cell population was increased in DCIS.com cells that expressed SOX11. Upregulating SOX11 expression in DCIS.com cells led to increased invasive growth both in vitro and when they were injected intraductally in a mouse model of DCIS that recapitulates human disease. Invasive lesions formed sooner and tumour growth was augmented in vivo, suggesting that SOX11 contributes to the progression of DCIS to invasive breast cancer. We identified potential downstream effectors of SOX11 during both microinvasive and invasive tumour growth stages, including several with established links to regulation of progenitor cell function and prenatal developmental growth. Our findings suggest that SOX11 is a potential biomarker for DCIS lesions containing cells harbouring distinct biological features that are likely to progress to invasive breast cancer. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Published
2017

28. Association of p16 expression with prognosis varies across ovarian carcinoma histotypes:an Ovarian Tumor Tissue Analysis consortium study

Author

Rambau, Peter F, Vierkant, Robert A, Intermaggio, Maria P, Kelemen, Linda E, Goodman, Marc T, Herpel, Esther, Pharoah, Paul D, Kommoss, Stefan, Jimenez-Linan, Mercedes, Karlan, Beth Y, Gentry-Maharaj, Aleksandra, Menon, Usha, Polo, Susanna Hernando, Candido Dos Reis, Francisco J, Doherty, Jennifer Anne, Gayther, Simon A, Sharma, Raghwa, Larson, Melissa C, Harnett, Paul R, Hatfield, Emma, De Andrade, Jurandyr M, Nelson, Gregg S, Steed, Helen, Schildkraut, Joellen M, Carney, Micheal E, Høgdall, Estrid, Whittemore, Alice S, Widschwendter, Martin, Kennedy, Catherine J, Wang, Frances, Wang, Qin, Wang, Chen, Armasu, Sebastian M, Daley, Frances, Coulson, Penny, Jones, Micheal E, Anglesio, Micheal S, Chow, Christine, De Fazio, Anna, García-Closas, Montserrat, Brucker, Sara Y, Cybulski, Cezary, Harris, Holly R, Hartkopf, Andreas D, Huzarski, Tomasz, Jensen, Allan, Lubiński, Jan, Oszurek, Oleg, Benitez, Javier, Mina, Fady, Staebler, Annette, Taran, Florin Andrei, Pasternak, Jana, Talhouk, Aline, Rossing, Mary Anne, Hendley, Joy, Edwards, Robert P, Fereday, Sian, Modugno, Francesmary, Ness, Roberta B, Sieh, Weiva, El-Bahrawy, Mona A, Winham, Stacey J, Lester, Jenny, Kjaer, Susanne K, Gronwald, Jacek, Sinn, Peter, Fasching, Peter A, Chang-Claude, Jenny, Moysich, Kirsten B, Bowtell, David D, Hernandez, Brenda Y, Luk, Hugh, Behrens, Sabine, Shah, Mitul, Jung, Audrey, Ghatage, Prafull, Alsop, Jennifer, Alsop, Kathryn, García-Donas, Jesús, Thompson, Pamela J, Swerdlow, Anthony J, Karpinskyj, Chloe, Cazorla-Jiménez, Alicia, García, María J, Deen, Susha, Wilkens, Lynne R, Palacios, José, Berchuck, Andrew, Koziak, Jennifer M, Brenton, James D, Cook, Linda S, Goode, Ellen L, Huntsman, David G, Ramus, Susan J, Köbel, Martin, Rambau, Peter F, Vierkant, Robert A, Intermaggio, Maria P, Kelemen, Linda E, Goodman, Marc T, Herpel, Esther, Pharoah, Paul D, Kommoss, Stefan, Jimenez-Linan, Mercedes, Karlan, Beth Y, Gentry-Maharaj, Aleksandra, Menon, Usha, Polo, Susanna Hernando, Candido Dos Reis, Francisco J, Doherty, Jennifer Anne, Gayther, Simon A, Sharma, Raghwa, Larson, Melissa C, Harnett, Paul R, Hatfield, Emma, De Andrade, Jurandyr M, Nelson, Gregg S, Steed, Helen, Schildkraut, Joellen M, Carney, Micheal E, Høgdall, Estrid, Whittemore, Alice S, Widschwendter, Martin, Kennedy, Catherine J, Wang, Frances, Wang, Qin, Wang, Chen, Armasu, Sebastian M, Daley, Frances, Coulson, Penny, Jones, Micheal E, Anglesio, Micheal S, Chow, Christine, De Fazio, Anna, García-Closas, Montserrat, Brucker, Sara Y, Cybulski, Cezary, Harris, Holly R, Hartkopf, Andreas D, Huzarski, Tomasz, Jensen, Allan, Lubiński, Jan, Oszurek, Oleg, Benitez, Javier, Mina, Fady, Staebler, Annette, Taran, Florin Andrei, Pasternak, Jana, Talhouk, Aline, Rossing, Mary Anne, Hendley, Joy, Edwards, Robert P, Fereday, Sian, Modugno, Francesmary, Ness, Roberta B, Sieh, Weiva, El-Bahrawy, Mona A, Winham, Stacey J, Lester, Jenny, Kjaer, Susanne K, Gronwald, Jacek, Sinn, Peter, Fasching, Peter A, Chang-Claude, Jenny, Moysich, Kirsten B, Bowtell, David D, Hernandez, Brenda Y, Luk, Hugh, Behrens, Sabine, Shah, Mitul, Jung, Audrey, Ghatage, Prafull, Alsop, Jennifer, Alsop, Kathryn, García-Donas, Jesús, Thompson, Pamela J, Swerdlow, Anthony J, Karpinskyj, Chloe, Cazorla-Jiménez, Alicia, García, María J, Deen, Susha, Wilkens, Lynne R, Palacios, José, Berchuck, Andrew, Koziak, Jennifer M, Brenton, James D, Cook, Linda S, Goode, Ellen L, Huntsman, David G, Ramus, Susan J, and Köbel, Martin

Published
2018

29. Abstract 788: Modeling tumor microenvironmental heterogeneity identifies CREBBP as a novel tumor suppressor in breast cancer

Author

Peck, Barrie, primary, Bland, Philip J., additional, Wai, Patty T., additional, Cottom, Hannah, additional, Maguire, Sarah L., additional, Morrison, Eamonn, additional, Barker, Holly E., additional, Kriplani, Divya, additional, Marlow, Rebecca, additional, Naidoo, Kalnisha, additional, Muirhead, Gareth, additional, Haider, Syed, additional, Daley, Frances, additional, Wallberg, Frederik, additional, Tutt, Andrew N., additional, and Natrajan, Rachael C., additional

Published
2018
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30. Optimised ARID1A immunohistochemistry is an accurate predictor ofARID1Amutational status in gynaecological cancers

Author

Khalique, Saira, primary, Naidoo, Kalnisha, additional, Attygalle, Ayoma D, additional, Kriplani, Divya, additional, Daley, Frances, additional, Lowe, Anne, additional, Campbell, James, additional, Jones, Thomas, additional, Hubank, Michael, additional, Fenwick, Kerry, additional, Matthews, Nicholas, additional, Rust, Alistair G, additional, Lord, Christopher J, additional, Banerjee, Susana, additional, and Natrajan, Rachael, additional

Published
2018
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31. Etiology of hormone receptor positive breast cancer differs by levels of histologic grade and proliferation

Author

Abubakar, Mustapha, primary, Chang‐Claude, Jenny, additional, Ali, H. Raza, additional, Chatterjee, Nilanjan, additional, Coulson, Penny, additional, Daley, Frances, additional, Blows, Fiona, additional, Benitez, Javier, additional, Milne, Roger L., additional, Brenner, Hermann, additional, Stegmaier, Christa, additional, Mannermaa, Arto, additional, Rudolph, Anja, additional, Sinn, Peter, additional, Couch, Fergus J., additional, Devilee, Peter, additional, Tollenaar, Rob A.E.M., additional, Seynaeve, Caroline, additional, Figueroa, Jonine, additional, Lissowska, Jolanta, additional, Hewitt, Stephen, additional, Hooning, Maartje J., additional, Hollestelle, Antoinette, additional, Foekens, Renée, additional, Koppert, Linetta B., additional, Investigators, kConFab, additional, Bolla, Manjeet K., additional, Wang, Qin, additional, Jones, Michael E., additional, Schoemaker, Minouk J., additional, Keeman, Renske, additional, Easton, Douglas F., additional, Swerdlow, Anthony J., additional, Sherman, Mark E., additional, Schmidt, Marjanka K., additional, Pharoah, Paul D., additional, and Garcia‐Closas, Montserrat, additional

Published
2018
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33. Evaluation of CDK12 Protein Expression as a Potential Novel Biomarker for DNA Damage Response–Targeted Therapies in Breast Cancer

Author

Naidoo, Kalnisha, primary, Wai, Patty T., additional, Maguire, Sarah L., additional, Daley, Frances, additional, Haider, Syed, additional, Kriplani, Divya, additional, Campbell, James, additional, Mirza, Hasan, additional, Grigoriadis, Anita, additional, Tutt, Andrew, additional, Moseley, Paul M., additional, Abdel-Fatah, Tarek M.A., additional, Chan, Stephen Y.T., additional, Madhusudan, Srinivasan, additional, Rhaka, Emad A., additional, Ellis, Ian O., additional, Lord, Christopher J., additional, Yuan, Yinyin, additional, Green, Andrew R., additional, and Natrajan, Rachael, additional

Published
2018
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34. Additional file 1: of Prognostic value of automated KI67 scoring in breast cancer: a centralised evaluation of 8088 patients from 10 study groups

Author

Abubakar, Mustapha, Orr, Nick, Daley, Frances, Coulson, Penny, H. Ali, Blows, Fiona, Benitez, Javier, Milne, Roger, Brenner, Herman, Stegmaier, Christa, Mannermaa, Arto, Chang-Claude, Jenny, Rudolph, Anja, Sinn, Peter, Couch, Fergus, Devilee, Peter, Tollenaar, Rob, Seynaeve, Caroline, Jonine Figueroa, Sherman, Mark, Lissowska, Jolanta, Hewitt, Stephen, Eccles, Diana, Hooning, Maartje, Hollestelle, Antoinette, Martens, John, Deurzen, Carolien, KConFab Investigators, Bolla, Manjeet, Wang, Qin, Jones, Michael, Minouk Schoemaker, Wesseling, Jelle, Leeuwen, Flora Van, Laura Van ‘T Veer, Easton, Douglas, Swerdlow, Anthony, Dowsett, Mitch, Pharoah, Paul, Marjanka Schmidt, and Garcia-Closas, Montserrat

Abstract

Is Table S1 presenting a description of study populations, Table S2 presenting KI67 immunohistochemistry reagents and antigen retrieval protocols according to study groups, Table S3 presenting the association of clinical and pathological characteristics with high (>12 %) and low (≤12 %) KI67 categories among 5520 ER-positive breast cancer cases, Table S4 presenting the association of clinical and pathological characteristics with high (>12 %) and low (≤12 %) KI67 categories among 2049 ER-negative breast cancer cases, Table S5 presenting cross-classification of visual and automated KI67 score categories, Table S6 presenting a multivariate model for the association of KI67 with 10-year BCSS among 5520 ER-positive patients, and Table S7 presenting a multivariate model for the association of KI67 with 10-year BCSS among 2049 ER-negative patients. (PDF 237 kb)

Published
2016
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36. Vessel co-option is common in human lung metastases and mediates resistance to anti-angiogenic therapy in preclinical lung metastasis models

Author

Bridgeman, Victoria L, primary, Vermeulen, Peter B, additional, Foo, Shane, additional, Bilecz, Agnes, additional, Daley, Frances, additional, Kostaras, Eleftherios, additional, Nathan, Mark R, additional, Wan, Elaine, additional, Frentzas, Sophia, additional, Schweiger, Thomas, additional, Hegedus, Balazs, additional, Hoetzenecker, Konrad, additional, Renyi-Vamos, Ferenc, additional, Kuczynski, Elizabeth A, additional, Vasudev, Naveen S, additional, Larkin, James, additional, Gore, Martin, additional, Dvorak, Harold F, additional, Paku, Sandor, additional, Kerbel, Robert S, additional, Dome, Balazs, additional, and Reynolds, Andrew R, additional

Published
2016
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38. Preclinical evaluation of the PARP inhibitor BMN-673 for the treatment of ovarian clear cell cancer

Author

Wilkerson, Paul M, primary, Dedes, Konstantin J, additional, Samartzis, Eleftherios Pierre, additional, Dedes, Ioannis, additional, Lambros, Maryou B, additional, Natrajan, Rachael, additional, Gauthier, Arnaud, additional, Piscuoglio, Salvatore, additional, Töpfer, Chantal, additional, Vukovic, Vesna, additional, Daley, Frances, additional, Weigelt, Britta, additional, and Reis-Filho, Jorge S, additional

Published
2016
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39. Crowdsourcing the General Public for Large Scale Molecular Pathology Studies in Cancer

Author

Candido Dos Reis, Francisco J, Lynn, Stuart, Ali, H Raza, Eccles, Diana, Hanby, Andrew, Provenzano, Elena, Caldas, Carlos, Howat, William J, McDuffus, Leigh-Anne, Liu, Bin, Daley, Frances, Coulson, Penny, Vyas, Rupesh J, Harris, Leslie M, Owens, Joanna M, Carton, Amy F M, McQuillan, Janette P, Paterson, Andy M, Hirji, Zohra, Christie, Sarah K, Holmes, Amber R, Schmidt, Marjanka K, Garcia-Closas, Montserrat, Easton, Douglas F, Bolla, Manjeet K, Wang, Qin, Milne, Roger L, Mannermaa, Arto, Couch, Fergus, Devilee, Peter, Tollenaar, Robert A E M, Seynaeve, Caroline, Cox, Angela, Cross, Simon S, Blows, Fiona M, Sanders, Joyce, de Groot, Renate, Figueroa, Jonine, Sherman, Mark, Hooning, Maartje, Brenner, Hermann, Holleczek, Bernd, Stegmaier, Christa, Lintott, Chris, Pharoah, Paul D P, Cancer Research UK (Reino Unido), KWF Kankerbestrijding, NIHR - Bristol Biomedical Research Centre (Reino Unido), and Instituto de Salud Carlos III

Subjects
BIOMARKER, Estrogen-receptor, Breast Neoplasms, Kaplan-Meier Estimate, Immunohistochemistry, Association, Breast cancer, ROC Curve, Receptors, Estrogen, Missing Data, Tissue Microarrays, SURVIVAL, Crowdsourcing, Humans, Female, Pathology, Molecular, Proportional Hazards Models
Abstract

Citizen science, scientific research conducted by non-specialists, has the potential to facilitate biomedical research using available large-scale data, however validating the results is challenging. The Cell Slider is a citizen science project that intends to share images from tumors with the general public, enabling them to score tumor markers independently through an internet-based interface. From October 2012 to June 2014, 98,293 Citizen Scientists accessed the Cell Slider web page and scored 180,172 sub-images derived from images of 12,326 tissue microarray cores labeled for estrogen receptor (ER). We evaluated the accuracy of Citizen Scientist's ER classification, and the association between ER status and prognosis by comparing their test performance against trained pathologists. The area under ROC curve was 0.95 (95% CI 0.94 to 0.96) for cancer cell identification and 0.97 (95% CI 0.96 to 0.97) for ER status. ER positive tumors scored by Citizen Scientists were associated with survival in a similar way to that scored by trained pathologists. Survival probability at 15 years were 0.78 (95% CI 0.76 to 0.80) for ER-positive and 0.72 (95% CI 0.68 to 0.77) for ER-negative tumors based on Citizen Scientists classification. Based on pathologist classification, survival probability was 0.79 (95% CI 0.77 to 0.81) for ER-positive and 0.71 (95% CI 0.67 to 0.74) for ER-negative tumors. The hazard ratio for death was 0.26 (95% CI 0.18 to 0.37) at diagnosis and became greater than one after 6.5 years of follow-up for ER scored by Citizen Scientists, and 0.24 (95% CI 0.18 to 0.33) at diagnosis increasing thereafter to one after 6.7 (95% CI 4.1 to 10.9) years of follow-up for ER scored by pathologists. Crowdsourcing of the general public to classify cancer pathology data for research is viable, engages the public and provides accurate ER data. Crowdsourced classification of research data may offer a valid solution to problems of throughput requiring human input. Cell Slider is supported by funding from Cancer Research UK. The individual studies were supported by grants from: Cancer Research UK (C490/A10124, C490/A16561), Dutch Cancer Society (NKI 2007-3839 and 2009-4363), the NIHR Biomedical Research Centre at the University of Cambridge, Yorkshire Cancer Research (S295, S299, S305PA), Red Tematica de Investigacion Cooperativa en Cancer, Fondo de Investigacion Sanitario (PI11/00923 and PI081120). The Human Genotyping-CEGEN Unit (CNIO) is supported by the Instituto de Salud Carlos III and the ESTHER study was supported by the Baden Wurttemberg Ministry of Science, Research and Arts. Sí

Published
2015

40. Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases

Author

Hubrecht Institute with UMC, CMM Sectie Molecular Cancer Research, Cancer, Frentzas, Sophia, Simoneau, Eve, Bridgeman, Victoria L., Vermeulen, Peter B., Foo, Shane, Kostaras, Eleftherios, Nathan, Mark R., Wotherspoon, Andrew, Gao, Zu Hua, Shi, Yu, Van Den Eynden, Gert, Daley, Frances, Peckitt, Clare, Tan, Xianming, Salman, Ayat, Lazaris, Anthoula, Gazinska, Patrycja, Berg, Tracy J., Eltahir, Zak, Ritsma, L., Van Rheenen, Jacco, Khashper, Alla, Brown, Gina, Nyström, Hanna, Sund, Malin, Van Laere, Steven, Loyer, Evelyne, Dirix, Luc, Cunningham, David, Metrakos, Peter, Reynolds, Andrew R., Hubrecht Institute with UMC, CMM Sectie Molecular Cancer Research, Cancer, Frentzas, Sophia, Simoneau, Eve, Bridgeman, Victoria L., Vermeulen, Peter B., Foo, Shane, Kostaras, Eleftherios, Nathan, Mark R., Wotherspoon, Andrew, Gao, Zu Hua, Shi, Yu, Van Den Eynden, Gert, Daley, Frances, Peckitt, Clare, Tan, Xianming, Salman, Ayat, Lazaris, Anthoula, Gazinska, Patrycja, Berg, Tracy J., Eltahir, Zak, Ritsma, L., Van Rheenen, Jacco, Khashper, Alla, Brown, Gina, Nyström, Hanna, Sund, Malin, Van Laere, Steven, Loyer, Evelyne, Dirix, Luc, Cunningham, David, Metrakos, Peter, and Reynolds, Andrew R.

Published
2016

41. Three‐dimensional modelling identifies novel genetic dependencies associated with breast cancer progression in the isogenic MCF10 model

Author

Maguire, Sarah L, primary, Peck, Barrie, additional, Wai, Patty T, additional, Campbell, James, additional, Barker, Holly, additional, Gulati, Aditi, additional, Daley, Frances, additional, Vyse, Simon, additional, Huang, Paul, additional, Lord, Christopher J, additional, Farnie, Gillian, additional, Brennan, Keith, additional, and Natrajan, Rachael, additional

Published
2016
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42. Prognostic value of automated KI67 scoring in breast cancer: a centralised evaluation of 8088 patients from 10 study groups

Author

Abubakar, Mustapha, primary, Orr, Nick, additional, Daley, Frances, additional, Coulson, Penny, additional, Ali, H. Raza, additional, Blows, Fiona, additional, Benitez, Javier, additional, Milne, Roger, additional, Brenner, Herman, additional, Stegmaier, Christa, additional, Mannermaa, Arto, additional, Chang-Claude, Jenny, additional, Rudolph, Anja, additional, Sinn, Peter, additional, Couch, Fergus J., additional, Devilee, Peter, additional, Tollenaar, Rob A. E. M., additional, Seynaeve, Caroline, additional, Figueroa, Jonine, additional, Sherman, Mark E., additional, Lissowska, Jolanta, additional, Hewitt, Stephen, additional, Eccles, Diana, additional, Hooning, Maartje J., additional, Hollestelle, Antoinette, additional, Martens, John W. M., additional, van Deurzen, Carolien H. M., additional, Investigators, kConFab, additional, Bolla, Manjeet K., additional, Wang, Qin, additional, Jones, Michael, additional, Schoemaker, Minouk, additional, Wesseling, Jelle, additional, van Leeuwen, Flora E., additional, Van ‘t Veer, Laura, additional, Easton, Douglas, additional, Swerdlow, Anthony J., additional, Dowsett, Mitch, additional, Pharoah, Paul D., additional, Schmidt, Marjanka K., additional, and Garcia-Closas, Montserrat, additional

Published
2016
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43. Dual Targeting of PDGFRα and FGFR1 Displays Synergistic Efficacy in Malignant Rhabdoid Tumors

Author

Wong, Jocelyn P., primary, Todd, Jason R., additional, Finetti, Martina A., additional, McCarthy, Frank, additional, Broncel, Malgorzata, additional, Vyse, Simon, additional, Luczynski, Maciej T., additional, Crosier, Stephen, additional, Ryall, Karen A., additional, Holmes, Kate, additional, Payne, Leo S., additional, Daley, Frances, additional, Wai, Patty, additional, Jenks, Andrew, additional, Tanos, Barbara, additional, Tan, Aik-Choon, additional, Natrajan, Rachael C., additional, Williamson, Daniel, additional, and Huang, Paul H., additional

Published
2016
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44. Co-option of Liver Vessels and Not Sprouting Angiogenesis Drives Acquired Sorafenib Resistance in Hepatocellular Carcinoma

Author

Kuczynski, Elizabeth A., primary, Yin, Melissa, additional, Bar-Zion, Avinoam, additional, Lee, Christina R., additional, Butz, Henriett, additional, Man, Shan, additional, Daley, Frances, additional, Vermeulen, Peter B., additional, Yousef, George M., additional, Foster, F. Stuart, additional, Reynolds, Andrew R., additional, and Kerbel, Robert S., additional

Published
2016
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45. High‐throughput automated scoring of Ki67 in breast cancer tissue microarrays from the Breast Cancer Association Consortium

Author

Abubakar, Mustapha, primary, Howat, William J, additional, Daley, Frances, additional, Zabaglo, Lila, additional, McDuffus, Leigh‐Anne, additional, Blows, Fiona, additional, Coulson, Penny, additional, Raza Ali, H, additional, Benitez, Javier, additional, Milne, Roger, additional, Brenner, Herman, additional, Stegmaier, Christa, additional, Mannermaa, Arto, additional, Chang‐Claude, Jenny, additional, Rudolph, Anja, additional, Sinn, Peter, additional, Couch, Fergus J, additional, Tollenaar, Rob A.E.M., additional, Devilee, Peter, additional, Figueroa, Jonine, additional, Sherman, Mark E, additional, Lissowska, Jolanta, additional, Hewitt, Stephen, additional, Eccles, Diana, additional, Hooning, Maartje J, additional, Hollestelle, Antoinette, additional, WM Martens, John, additional, HM van Deurzen, Carolien, additional, Investigators, kConFab, additional, Bolla, Manjeet K, additional, Wang, Qin, additional, Jones, Michael, additional, Schoemaker, Minouk, additional, Broeks, Annegien, additional, van Leeuwen, Flora E, additional, Van't Veer, Laura, additional, Swerdlow, Anthony J, additional, Orr, Nick, additional, Dowsett, Mitch, additional, Easton, Douglas, additional, Schmidt, Marjanka K, additional, Pharoah, Paul D, additional, and Garcia‐Closas, Montserrat, additional

Published
2016
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47. Performance of automated scoring of ER, PR, HER2, CK5/6 and EGFR in breast cancer tissue microarrays in the Breast Cancer Association Consortium

Author

Howat, William J, Blows, Fiona M, Provenzano, Elena, Brook, Mark N, Morris, Lorna, Gazinska, Patrycja, Johnson, Nicola, McDuffus, Leigh-Anne, Miller, Jodi, Sawyer, Elinor J, Pinder, Sarah, van Deurzen, Carolien H M, Jones, Louise, Sironen, Reijo, Visscher, Daniel, Caldas, Carlos, Daley, Frances, Coulson, Penny, Broeks, Annegien, Sanders, Joyce, Wesseling, Jelle, Nevanlinna, Heli, Fagerholm, Rainer, Blomqvist, Carl, Heikkilä, Päivi, Ali, H Raza, Dawson, Sarah-Jane, Figueroa, Jonine, Lissowska, Jolanta, Brinton, Louise, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Cox, Angela, Brock, Ian W, Cross, Simon S, Reed, Malcolm W, Couch, Fergus J, Olson, Janet E, Devillee, Peter, Mesker, Wilma E, Seyaneve, Caroline M, Hollestelle, Antoinette, Benitez, Javier, Perez, Jose Ignacio Arias, Menéndez, Primitiva, Bolla, Manjeet K, Easton, Douglas F, Schmidt, Marjanka K, Pharoah, Paul D, Sherman, Mark E, García-Closas, Montserrat, Howat, William J, Blows, Fiona M, Provenzano, Elena, Brook, Mark N, Morris, Lorna, Gazinska, Patrycja, Johnson, Nicola, McDuffus, Leigh-Anne, Miller, Jodi, Sawyer, Elinor J, Pinder, Sarah, van Deurzen, Carolien H M, Jones, Louise, Sironen, Reijo, Visscher, Daniel, Caldas, Carlos, Daley, Frances, Coulson, Penny, Broeks, Annegien, Sanders, Joyce, Wesseling, Jelle, Nevanlinna, Heli, Fagerholm, Rainer, Blomqvist, Carl, Heikkilä, Päivi, Ali, H Raza, Dawson, Sarah-Jane, Figueroa, Jonine, Lissowska, Jolanta, Brinton, Louise, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Cox, Angela, Brock, Ian W, Cross, Simon S, Reed, Malcolm W, Couch, Fergus J, Olson, Janet E, Devillee, Peter, Mesker, Wilma E, Seyaneve, Caroline M, Hollestelle, Antoinette, Benitez, Javier, Perez, Jose Ignacio Arias, Menéndez, Primitiva, Bolla, Manjeet K, Easton, Douglas F, Schmidt, Marjanka K, Pharoah, Paul D, Sherman, Mark E, and García-Closas, Montserrat

Abstract

Breast cancer risk factors and clinical outcomes vary by tumour marker expression. However, individual studies often lack the power required to assess these relationships, and large-scale analyses are limited by the need for high throughput, standardized scoring methods. To address these limitations, we assessed whether automated image analysis of immunohistochemically stained tissue microarrays can permit rapid, standardized scoring of tumour markers from multiple studies. Tissue microarray sections prepared in nine studies containing 20 263 cores from 8267 breast cancers stained for two nuclear (oestrogen receptor, progesterone receptor), two membranous (human epidermal growth factor receptor 2 and epidermal growth factor receptor) and one cytoplasmic (cytokeratin 5/6) marker were scanned as digital images. Automated algorithms were used to score markers in tumour cells using the Ariol system. We compared automated scores against visual reads, and their associations with breast cancer survival. Approximately 65-70% of tissue microarray cores were satisfactory for scoring. Among satisfactory cores, agreement between dichotomous automated and visual scores was highest for oestrogen receptor (Kappa = 0.76), followed by human epidermal growth factor receptor 2 (Kappa = 0.69) and progesterone receptor (Kappa = 0.67). Automated quantitative scores for these markers were associated with hazard ratios for breast cancer mortality in a dose-response manner. Considering visual scores of epidermal growth factor receptor or cytokeratin 5/6 as the reference, automated scoring achieved excellent negative predictive value (96-98%), but yielded many false positives (positive predictive value = 30-32%). For all markers, we observed substantial heterogeneity in automated scoring performance across tissue microarrays. Automated analysis is a potentially useful tool for large-scale, quantitative scoring of immunohistochemically stained tissue microarrays available in consortia. How

Published
2015

48. Crowdsourcing the General Public for Large Scale Molecular Pathology Studies in Cancer

Author

Candido dos Reis, Francisco J., primary, Lynn, Stuart, additional, Ali, H. Raza, additional, Eccles, Diana, additional, Hanby, Andrew, additional, Provenzano, Elena, additional, Caldas, Carlos, additional, Howat, William J., additional, McDuffus, Leigh-Anne, additional, Liu, Bin, additional, Daley, Frances, additional, Coulson, Penny, additional, Vyas, Rupesh J., additional, Harris, Leslie M., additional, Owens, Joanna M., additional, Carton, Amy F.M., additional, McQuillan, Janette P., additional, Paterson, Andy M., additional, Hirji, Zohra, additional, Christie, Sarah K., additional, Holmes, Amber R., additional, Schmidt, Marjanka K., additional, Garcia-Closas, Montserrat, additional, Easton, Douglas F., additional, Bolla, Manjeet K., additional, Wang, Qin, additional, Benitez, Javier, additional, Milne, Roger L., additional, Mannermaa, Arto, additional, Couch, Fergus, additional, Devilee, Peter, additional, Tollenaar, Robert A.E.M., additional, Seynaeve, Caroline, additional, Cox, Angela, additional, Cross, Simon S., additional, Blows, Fiona M., additional, Sanders, Joyce, additional, de Groot, Renate, additional, Figueroa, Jonine, additional, Sherman, Mark, additional, Hooning, Maartje, additional, Brenner, Hermann, additional, Holleczek, Bernd, additional, Stegmaier, Christa, additional, Lintott, Chris, additional, and Pharoah, Paul D.P., additional

Published
2015
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49. Performance of automated scoring of ER, PR, HER2, CK5/6 and EGFR in breast cancer tissue microarrays in the Breast Cancer Association Consortium

Author

Howat, William J, primary, Blows, Fiona M, additional, Provenzano, Elena, additional, Brook, Mark N, additional, Morris, Lorna, additional, Gazinska, Patrycja, additional, Johnson, Nicola, additional, McDuffus, Leigh-Anne, additional, Miller, Jodi, additional, Sawyer, Elinor J, additional, Pinder, Sarah, additional, van Deurzen, Carolien H M, additional, Jones, Louise, additional, Sironen, Reijo, additional, Visscher, Daniel, additional, Caldas, Carlos, additional, Daley, Frances, additional, Coulson, Penny, additional, Broeks, Annegien, additional, Sanders, Joyce, additional, Wesseling, Jelle, additional, Nevanlinna, Heli, additional, Fagerholm, Rainer, additional, Blomqvist, Carl, additional, Heikkilä, Päivi, additional, Ali, H Raza, additional, Dawson, Sarah-Jane, additional, Figueroa, Jonine, additional, Lissowska, Jolanta, additional, Brinton, Louise, additional, Mannermaa, Arto, additional, Kataja, Vesa, additional, Kosma, Veli-Matti, additional, Cox, Angela, additional, Brock, Ian W, additional, Cross, Simon S, additional, Reed, Malcolm W, additional, Couch, Fergus J, additional, Olson, Janet E, additional, Devillee, Peter, additional, Mesker, Wilma E, additional, Seyaneve, Caroline M, additional, Hollestelle, Antoinette, additional, Benitez, Javier, additional, Perez, Jose Ignacio Arias, additional, Menéndez, Primitiva, additional, Bolla, Manjeet K, additional, Easton, Douglas F, additional, Schmidt, Marjanka K, additional, Pharoah, Paul D, additional, Sherman, Mark E, additional, and García-Closas, Montserrat, additional

Published
2014
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