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2. The 2019 International Society of Urological Pathology (ISUP) Consensus Conference on Grading of Prostatic Carcinoma

Author

Leenders, G.J.H.L. (Geert), Kwast, Th.H. (Theo) van der, Grignon, D.J. (David J.), Evans, A.J. (Andrew J.), Kristiansen, G. (Glen), Kweldam, C.F. (Charlotte), Litjens, G. (Geert), McKenney, J.K. (Jesse K.), Melamed, J. (Jonathan), Mottet, N. (Nicolas), Paner, G.P. (Gladell P.), Samaratunga, H. (Hemamali), Schoots, I.G. (Ivo), Simko, J. (Jeff), Tsuzuki, T. (Toyonori), Varma, M. (Murali), Warren, A.Y. (Anne Y.), Wheeler, T.M. (Thomas), Williamson, S.R. (Sean R.), Iczkowski, K.A. (Kenneth A.), Leenders, G.J.H.L. (Geert), Kwast, Th.H. (Theo) van der, Grignon, D.J. (David J.), Evans, A.J. (Andrew J.), Kristiansen, G. (Glen), Kweldam, C.F. (Charlotte), Litjens, G. (Geert), McKenney, J.K. (Jesse K.), Melamed, J. (Jonathan), Mottet, N. (Nicolas), Paner, G.P. (Gladell P.), Samaratunga, H. (Hemamali), Schoots, I.G. (Ivo), Simko, J. (Jeff), Tsuzuki, T. (Toyonori), Varma, M. (Murali), Warren, A.Y. (Anne Y.), Wheeler, T.M. (Thomas), Williamson, S.R. (Sean R.), and Iczkowski, K.A. (Kenneth A.)

Abstract

Five years after the last prostatic carcinoma grading consensus conference of the International Society of Urological Pathology (ISUP), accrual of new data and modification of clinical practice require an update of current pathologic grading guidelines. This manuscript summarizes the proceedings of the ISUP consensus meeting for grading of prostatic carcinoma held in September 2019, in Nice, France. Topics brought to consensus included the following: (1) approaches to reporting of Gleason patterns 4 and 5 quantities, and minor/tertiary patterns, (2) an agreement to report the presence of invasive cribriform carcinoma, (3) an agreement to incorporate intraductal carcinoma into grading, and (4) individual versus aggregate grading of systematic and multiparametric magnetic resonance imaging-targeted biopsies. Finally, developments in the field of artificial intelligence in the grading of prostatic carcinoma and future research perspectives were discussed.

Published
2020
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4. A comparison of endothelium-dependent relaxation in omental and myometrial resistance arteries in pregnant and nonpregnant

Author

Ashworth, Janet R., Warren, A.Y., Baker, P.N., and Johnson, I.R.

Subjects
Blood vessels -- Dilatation, Pregnancy -- Physiological aspects, Arteries -- Physiological aspects, Health
Abstract

Abdominal arteries may have a greater relaxation response to bradykinin than uterine arteries in both pregnant and nonpregnant women. Researchers obtained omental (abdominal) and uterine muscle arteries from 22 pregnant and 27 nonpregnant women. Arteries were constricted with vasopressin, and then relaxed with bradykinin. Omental arteries relaxed more than did uterine muscle arteries in both pregnant and nonpregnant women. No difference was seen in the blood vessel relaxation response between pregnant and nonpregnant women.

Published
1996

5. Can computer-aided diagnosis assist in the identification of prostate cancer on prostate MRI? a multi-center, multi-reader investigation

Author

Gaur, S., Lay, N., Harmon, S.A., Doddakashi, S., Mehralivand, S., Argun, B., Barrett, T., Bednarova, S., Girometti, R., Karaarslan, E., Kural, A.R., Oto, A., Purysko, A.S., Antic, T., Magi-Galluzzi, C., Saglican, Y., Sioletic, S., Warren, A.Y., Bittencourt, L., Futterer, J.J., Gupta, R.T., Kabakus, I., Law, Y.M., Margolis, D.J., Shebel, H., Westphalen, A.C., Wood, B.J., Pinto, P.A., Shih, J.H., Choyke, P.L., Summers, R.M., Turkbey, B., Gaur, S., Lay, N., Harmon, S.A., Doddakashi, S., Mehralivand, S., Argun, B., Barrett, T., Bednarova, S., Girometti, R., Karaarslan, E., Kural, A.R., Oto, A., Purysko, A.S., Antic, T., Magi-Galluzzi, C., Saglican, Y., Sioletic, S., Warren, A.Y., Bittencourt, L., Futterer, J.J., Gupta, R.T., Kabakus, I., Law, Y.M., Margolis, D.J., Shebel, H., Westphalen, A.C., Wood, B.J., Pinto, P.A., Shih, J.H., Choyke, P.L., Summers, R.M., and Turkbey, B.

Abstract

Contains fulltext : 199964.pdf (Publisher’s version ) (Open Access), For prostate cancer detection on prostate multiparametric MRI (mpMRI), the Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) and computer-aided diagnosis (CAD) systems aim to widely improve standardization across radiologists and centers. Our goal was to evaluate CAD assistance in prostate cancer detection compared with conventional mpMRI interpretation in a diverse dataset acquired from five institutions tested by nine readers of varying experience levels, in total representing 14 globally spread institutions. Index lesion sensitivities of mpMRI-alone were 79% (whole prostate (WP)), 84% (peripheral zone (PZ)), 71% (transition zone (TZ)), similar to CAD at 76% (WP, p=0.39), 77% (PZ, p=0.07), 79% (TZ, p=0.15). Greatest CAD benefit was in TZ for moderately-experienced readers at PI-RADSv2 <3 (84% vs mpMRI-alone 67%, p=0.055). Detection agreement was unchanged but CAD-assisted read times improved (4.6 vs 3.4 minutes, p<0.001). At PI-RADSv2 >/= 3, CAD improved patient-level specificity (72%) compared to mpMRI-alone (45%, p<0.001). PI-RADSv2 and CAD-assisted mpMRI interpretations have similar sensitivities across multiple sites and readers while CAD has potential to improve specificity and moderately-experienced radiologists' detection of more difficult tumors in the center of the gland. The multi-institutional evidence provided is essential to future prostate MRI and CAD development.

Published
2018

7. Corrigendum to “Comprehensive assessment of estrogen receptor beta antibodies in cancer cell line models and tissue reveals critical limitations in reagent specificity” [Mol. Cell Endocrinol. 440 (2016) 138–150]

Author

Nelson, A.W., primary, Groen, A.J., additional, Miller, J.L., additional, Warren, A.Y., additional, Holmes, K.A., additional, Tarulli, G.A., additional, Tilley, W.D., additional, Katzenellenbogen, B.S., additional, Hawse, J.R., additional, Gnanapragasam, V.J., additional, and Carroll, J.S., additional

Published
2017
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8. Corrigendum to “Integration of Copy Number and Transcriptomics Provides Risk Stratification in Prostate Cancer: A Discovery and Validation Cohort Study” [EBioMedicine 2 (9) (2015) 1133–1144]

Author

Ross-Adams, H., primary, Lamb, A.D., additional, Dunning, M.J., additional, Halim, S., additional, Lindberg, J., additional, Massie, C.M., additional, Egevad, L.A., additional, Russell, R., additional, Ramos-Montoya, A., additional, Vowler, S.L., additional, Sharma, N.L., additional, Kay, J., additional, Whitaker, H., additional, Clark, J., additional, Hurst, R., additional, Gnanapragasam, V.J., additional, Shah, N.C., additional, Warren, A.Y., additional, Cooper, C.S., additional, Lynch, A.G., additional, Stark, R., additional, Mills, I.G., additional, Grönberg, H., additional, and Neal, D.E., additional

Published
2017
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9. The rs10993994 risk allele for prostate cancer results in clinically relevant changes in microseminoprotein-beta expression in tissue and urine

Author

Vickers, A., Whitaker, H. C., Kote-Jarai, Z., Ross-Adams, H., Warren, A.Y., Burge, J., George, A., Bancroft, E., Jhavar, S., Leongamornlert, D., Tymrakiewicz, M., Saunders, E., Page, E., Mitra, A., Mitchell, G., Lindeman, G.J., Evans, D. G., Blanco, I., Mercer, C., Rubinstein, W.S., Clowes, V., Douglas, F., Hodgson, S., Walker, L., Donaldson, A., Izatt, L., Dorkins, H., Male, A., Tucker, K., Stapleton, A., Lam, J., Kirk, J., Lilja, H., Easton, D., Cooper, C., Eeles, R., Neal, D.E., and Tobias, E.S.

Subjects
QH426, R1
Abstract

Background:\ud \ud Microseminoprotein-beta (MSMB) regulates apoptosis and using genome-wide association studies the rs10993994 single nucleotide polymorphism in the MSMB promoter has been linked to an increased risk of developing prostate cancer. The promoter location of the risk allele, and its ability to reduce promoter activity, suggested that the rs10993994 risk allele could result in lowered MSMB in benign tissue leading to increased prostate cancer risk.\ud Methodology/Principal Findings:\ud MSMB expression in benign and malignant prostate tissue was examined using immunohistochemistry and compared with the rs10993994 genotype. Urinary MSMB concentrations were determined by ELISA and correlated with urinary PSA, the presence or absence of cancer, rs10993994 genotype and age of onset. MSMB levels in prostate tissue and urine were greatly reduced with tumourigenesis. Urinary MSMB was better than urinary PSA at differentiating men with prostate cancer at all Gleason grades. The high risk allele was associated with heterogeneity of MSMB staining and loss of MSMB in both tissue and urine in benign prostate.\ud Conclusions:\ud These data show that some high risk alleles discovered using genome-wide association studies produce phenotypic effects with potential clinical utility. We provide the first link between a low penetrance polymorphism for prostate cancer and a potential test in human tissue and bodily fluids. There is potential to develop tissue and urinary MSMB for a biomarker of prostate cancer risk, diagnosis and disease monitoring.

Published
2010

10. Integration of copy number and transcriptomics provides risk stratification in prostate cancer: A discovery and validation cohort study

Author

Ross-Adams, H., primary, Lamb, A.D., additional, Dunning, M.J., additional, Halim, S., additional, Lindberg, J., additional, Massie, C.M., additional, Egevad, L.A., additional, Russell, R., additional, Ramos-Montoya, A., additional, Vowler, S.L., additional, Sharma, N.L., additional, Kay, J., additional, Whitaker, H., additional, Clark, J., additional, Hurst, R., additional, Gnanapragasam, V.J., additional, Shah, N.C., additional, Warren, A.Y., additional, Cooper, C.S., additional, Lynch, A.G., additional, Stark, R., additional, Mills, I.G., additional, Grönberg, H., additional, and Neal, D.E., additional

Published
2015
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11. Mobile DNA in cancer. Extensive transduction of nonrepetitive DNA mediated by L1 retrotransposition in cancer genomes.

Author

Tubio, J.M., Li, Y., Ju, Y.S., Martincorena, I., Cooke, S.L., Tojo, M., Gundem, G., Pipinikas, C.P., Zamora, J., Raine, K., Menzies, A., Roman-Garcia, P., Fullam, A., Gerstung, M., Shlien, A., Tarpey, P.S., Papaemmanuil, E., Knappskog, S., Loo, P. Van, Ramakrishna, M., Davies, H.R., Marshall, J., Wedge, D.C., Teague, J.W., Butler, A.P., Nik-Zainal, S., Alexandrov, L., Behjati, S., Yates, L.R., Bolli, N., Mudie, L., Hardy, C., Martin, S., McLaren, S., O'Meara, S., Anderson, E., Maddison, M., Gamble, S., Foster, C., Warren, A.Y., Whitaker, H., Brewer, D., Eeles, R., Cooper, C., Neal, D., Lynch, A.G., Visakorpi, T., Isaacs, W.B., n't Veer, L. va, Caldas, C., Desmedt, C., Sotiriou, C., Aparicio, S., Foekens, J.A., Eyfjord, J.E., Lakhani, S.R., Thomas, G., Myklebost, O., Span, P.N., Borresen-Dale, A.L., Richardson, A.L., Vijver, M. van de, Vincent-Salomon, A., Eynden, G.G. Van den, Flanagan, A.M., Futreal, P.A., Janes, S.M., Bova, G.S., Stratton, M.R., McDermott, U., Campbell, P.J., Tubio, J.M., Li, Y., Ju, Y.S., Martincorena, I., Cooke, S.L., Tojo, M., Gundem, G., Pipinikas, C.P., Zamora, J., Raine, K., Menzies, A., Roman-Garcia, P., Fullam, A., Gerstung, M., Shlien, A., Tarpey, P.S., Papaemmanuil, E., Knappskog, S., Loo, P. Van, Ramakrishna, M., Davies, H.R., Marshall, J., Wedge, D.C., Teague, J.W., Butler, A.P., Nik-Zainal, S., Alexandrov, L., Behjati, S., Yates, L.R., Bolli, N., Mudie, L., Hardy, C., Martin, S., McLaren, S., O'Meara, S., Anderson, E., Maddison, M., Gamble, S., Foster, C., Warren, A.Y., Whitaker, H., Brewer, D., Eeles, R., Cooper, C., Neal, D., Lynch, A.G., Visakorpi, T., Isaacs, W.B., n't Veer, L. va, Caldas, C., Desmedt, C., Sotiriou, C., Aparicio, S., Foekens, J.A., Eyfjord, J.E., Lakhani, S.R., Thomas, G., Myklebost, O., Span, P.N., Borresen-Dale, A.L., Richardson, A.L., Vijver, M. van de, Vincent-Salomon, A., Eynden, G.G. Van den, Flanagan, A.M., Futreal, P.A., Janes, S.M., Bova, G.S., Stratton, M.R., McDermott, U., and Campbell, P.J.

Abstract

Item does not contain fulltext, Long interspersed nuclear element-1 (L1) retrotransposons are mobile repetitive elements that are abundant in the human genome. L1 elements propagate through RNA intermediates. In the germ line, neighboring, nonrepetitive sequences are occasionally mobilized by the L1 machinery, a process called 3' transduction. Because 3' transductions are potentially mutagenic, we explored the extent to which they occur somatically during tumorigenesis. Studying cancer genomes from 244 patients, we found that tumors from 53% of the patients had somatic retrotranspositions, of which 24% were 3' transductions. Fingerprinting of donor L1s revealed that a handful of source L1 elements in a tumor can spawn from tens to hundreds of 3' transductions, which can themselves seed further retrotranspositions. The activity of individual L1 elements fluctuated during tumor evolution and correlated with L1 promoter hypomethylation. The 3' transductions disseminated genes, exons, and regulatory elements to new locations, most often to heterochromatic regions of the genome.

Published
2014

12. Extensive transduction of nonrepetitive DNA mediated by L1 retrotransposition in cancer genomes

Author

Tubio, J.M.C. (Jose M.), Li, Y. (Yilong), Ju, Y.S. (Young Seok), Martincorena, I. (Inigo), Cooke, S.L. (Susanna), Tojo, M. (Marta), Gundem, G. (Gunes), Pipinikas, C.P. (Christodoulos), Zamora, J. (Jorge), Raine, (Keiran), Menzies, D., Roman-Garcia, P. (Pablo), Fullam, A. (Anthony), Gerstung, M. (Moritz), Shlien, A. (Adam), Tarpey, P.S. (Patrick), Papaemmanuil, E. (Elli), Knappskog, S. (Stian), Loo, P. (Peter) van, Ramakrishna, M. (Manasa), Davies, H. (Helen), Marshall, J. (John), Wedge, D.C. (David), Teague, J. (Jon), Butler, A. (Adam), Nik-Zainal, S. (Serena), Alexandrov, L.B. (Ludmil), Behjati, S. (Sam), Yates, L.R. (Lucy), Bolli, N. (Niccolò), Mudie, L. (Laura), Hardy, C. (Claire), Martin, S. (Sandra), McLaren, S. (Stuart), O'Meara, S. (Sarah), Anderson, E. (Elizabeth), Maddison, M. (Mark), Gamble, S. (Stephen), Foster, C.S. (Christopher), Warren, A.Y. (Anne), Whitaker, H.J. (Heather), Brewer, D. (Daniel), Eeles, R. (Rosalind), Cooper, C. (Colin), Neal, D. (David), Lynch, A.G. (Andy), Visakorpi, T. (Tapio), Isaacs, W.B. (William), Veer, L.J. (Laura) van 't, Caldas, C. (Carlos), Desmedt, C. (Christine), Sotiriou, C. (Christos), Aparicio, S. (Sam), Foekens, J.A. (John), Eyfjord, J., Lakhani, S. (Sunil), Thomas, G. (Gilles), Myklebost, O. (Ola), Span, P.N. (Paul), Børresen-Dale, A.L. (Anne Lise), Richardson, A.L. (Andrea), Vijver, M.J. (Marc ), Vincent-Salomon, A. (Anne), Eynden, G.G. (Gert) van den, Flanagan, A.M. (Adrienne), Futreal, P.A. (Andrew), Janes, H. (Holly), Bova, G.S. (G. Steven), Stratton, M.R. (Michael), McDermott, U. (Ultan), Campbell, P.J. (Peter), Tubio, J.M.C. (Jose M.), Li, Y. (Yilong), Ju, Y.S. (Young Seok), Martincorena, I. (Inigo), Cooke, S.L. (Susanna), Tojo, M. (Marta), Gundem, G. (Gunes), Pipinikas, C.P. (Christodoulos), Zamora, J. (Jorge), Raine, (Keiran), Menzies, D., Roman-Garcia, P. (Pablo), Fullam, A. (Anthony), Gerstung, M. (Moritz), Shlien, A. (Adam), Tarpey, P.S. (Patrick), Papaemmanuil, E. (Elli), Knappskog, S. (Stian), Loo, P. (Peter) van, Ramakrishna, M. (Manasa), Davies, H. (Helen), Marshall, J. (John), Wedge, D.C. (David), Teague, J. (Jon), Butler, A. (Adam), Nik-Zainal, S. (Serena), Alexandrov, L.B. (Ludmil), Behjati, S. (Sam), Yates, L.R. (Lucy), Bolli, N. (Niccolò), Mudie, L. (Laura), Hardy, C. (Claire), Martin, S. (Sandra), McLaren, S. (Stuart), O'Meara, S. (Sarah), Anderson, E. (Elizabeth), Maddison, M. (Mark), Gamble, S. (Stephen), Foster, C.S. (Christopher), Warren, A.Y. (Anne), Whitaker, H.J. (Heather), Brewer, D. (Daniel), Eeles, R. (Rosalind), Cooper, C. (Colin), Neal, D. (David), Lynch, A.G. (Andy), Visakorpi, T. (Tapio), Isaacs, W.B. (William), Veer, L.J. (Laura) van 't, Caldas, C. (Carlos), Desmedt, C. (Christine), Sotiriou, C. (Christos), Aparicio, S. (Sam), Foekens, J.A. (John), Eyfjord, J., Lakhani, S. (Sunil), Thomas, G. (Gilles), Myklebost, O. (Ola), Span, P.N. (Paul), Børresen-Dale, A.L. (Anne Lise), Richardson, A.L. (Andrea), Vijver, M.J. (Marc ), Vincent-Salomon, A. (Anne), Eynden, G.G. (Gert) van den, Flanagan, A.M. (Adrienne), Futreal, P.A. (Andrew), Janes, H. (Holly), Bova, G.S. (G. Steven), Stratton, M.R. (Michael), McDermott, U. (Ultan), and Campbell, P.J. (Peter)

Abstract

Long interspersed nuclear element–1 (L1) retrotransposons are mobile repetitive elements that are abundant in the human genome. L1 elements propagate through RNA intermediates. In the germ line, neighboring, nonrepetitive sequences are occasionally mobilized by the L1 machinery, a process called 3′ transduction. Because 3′ transductions are potentially mutagenic, we explored the extent to which they occur somatically during tumorigenesis. Studying cancer genomes from 244 patients, we found that tumors from 53% of the patients had somatic retrotranspositions, of which 24% were 3′ transductions. Fingerprinting of donor L1s revealed that a handful of source L1 elements in a tumor can spawn from tens to hundreds of 3′ transductions, which can themselves seed further retrotranspositions. The activity of individual L1 elements fluctuated during tumor evolution and correlated with L1 promoter hypomethylation. The 3′ transductions disseminated genes, exons, and regulatory elements to new locations, most often to heterochromatic regions of the genome.

Published
2014
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13. 836 Hes6 drives a critical androgen receptor (AR) transcriptional program to induce castration resistant prostate cancer (CRPC) through activation of an E2F1-mediated cell cycle network

Author

Lamb, A.D., primary, Ramos-Montoya, A., additional, Russell, R., additional, Carroll, T., additional, Massie, C.E., additional, Shaw, G., additional, Sharma, N.L., additional, Warren, A.Y., additional, Wooster, R.F., additional, Mills, I.G., additional, and Neal, D.E., additional

Published
2014
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14. The rs10993994 risk allele for prostate cancer results in clinically relevant changes in microseminoprotein-beta expression in tissue and urine.

Author

Whitaker, H.C., Kote-Jarai, Z., Ross-Adams, H., Warren, A.Y., Burge, J., George, A., Bancroft, E., Jhavar, S., Leongamornlert, D., Tymrakiewicz, M., Saunders, E., Page, E., Mitra, A., Mitchell, G., Lindeman, G.J., Evans, D.G., Blanco, I., Mercer, C., Rubinstein, W.S., Clowes, V., Douglas, F., Hodgson, S., Walker, L., Donaldson, A., Izatt, L., Dorkins, H., Male, A., Tucker, K., Stapleton, A., Lam, J., Kirk, J., Lilja, H., Easton, D., Cooper, C., Eeles, R., Neal, D.E., Whitaker, H.C., Kote-Jarai, Z., Ross-Adams, H., Warren, A.Y., Burge, J., George, A., Bancroft, E., Jhavar, S., Leongamornlert, D., Tymrakiewicz, M., Saunders, E., Page, E., Mitra, A., Mitchell, G., Lindeman, G.J., Evans, D.G., Blanco, I., Mercer, C., Rubinstein, W.S., Clowes, V., Douglas, F., Hodgson, S., Walker, L., Donaldson, A., Izatt, L., Dorkins, H., Male, A., Tucker, K., Stapleton, A., Lam, J., Kirk, J., Lilja, H., Easton, D., Cooper, C., Eeles, R., and Neal, D.E.

Abstract

Contains fulltext : 87729.pdf (publisher's version ) (Open Access), BACKGROUND: Microseminoprotein-beta (MSMB) regulates apoptosis and using genome-wide association studies the rs10993994 single nucleotide polymorphism in the MSMB promoter has been linked to an increased risk of developing prostate cancer. The promoter location of the risk allele, and its ability to reduce promoter activity, suggested that the rs10993994 risk allele could result in lowered MSMB in benign tissue leading to increased prostate cancer risk. METHODOLOGY/PRINCIPAL FINDINGS: MSMB expression in benign and malignant prostate tissue was examined using immunohistochemistry and compared with the rs10993994 genotype. Urinary MSMB concentrations were determined by ELISA and correlated with urinary PSA, the presence or absence of cancer, rs10993994 genotype and age of onset. MSMB levels in prostate tissue and urine were greatly reduced with tumourigenesis. Urinary MSMB was better than urinary PSA at differentiating men with prostate cancer at all Gleason grades. The high risk allele was associated with heterogeneity of MSMB staining and loss of MSMB in both tissue and urine in benign prostate. CONCLUSIONS: These data show that some high risk alleles discovered using genome-wide association studies produce phenotypic effects with potential clinical utility. We provide the first link between a low penetrance polymorphism for prostate cancer and a potential test in human tissue and bodily fluids. There is potential to develop tissue and urinary MSMB for a biomarker of prostate cancer risk, diagnosis and disease monitoring.

Published
2010

22. Generation of angiotensin I by human chorion-decidua in vitro

Author

Craven, D.J., Warren, A.Y., and Symonds, E.M.

Abstract

An angiotensin I-like substance has been detected in media after incubation of human chorion-decidua in vitro. The substance was identified as angiotensin I by gel filtration, ion exchange chromatography, and a specific antiserum to angiotensin I. The presence of angiotensin I in these incubates indicates that renin substrate may be either stored or synthesized by the tissue. The levels of angiotensin I produced during incubation were greater than could be explained by the action of renin on plasma substrate since the major part of the chorion-decidua is avascular. Previously chorion-decidua has been shown to contain large amounts of renin and to be capable of synthesizing both active and inactive forms of the enzyme in vitro; however, renin substrate has not been described in this tissue.

Published
1983
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25. PROBLEMS WITH AUDIT IN CERVICAL CYTOLOGY.

Author

Womack, C. and Warren, A.Y.

Subjects
*CYTOLOGY, *CERVIX uteri diseases, *AUDITING
Abstract

Comments on problems encountered with audit in cervical cytology in the U.S. Incidence of false positive smears; Value of aggregated data in the investigation of cervical cancer; Need for audit processes to be protected from disclosure in cases of litigation.

Published
2000
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26. Hyperpolarized 13C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma-A Proof of Principle Study

Author

Ursprung, Stephan, Woitek, Ramona, McLean, Mary, Priest, Andrew N, Crispin-Ortuzar, Mireia, Brodie, Cara R, Gill, Andrew, Gehrung, Marcel, Beer, Lucian, Riddick, Antony CP, Field-Rayner, Johanna, Grist, James T, Deen, Surrin S, Riemer, Frank, Kaggie, Joshua, Zaccagna, Fulvio, Duarte, Joao AG, Locke, Matthew J, Frary, Amy, Aho, Tevita F, Armitage, James N, Casey, Ruth, Mendichovszky, Iosif A, Welsh, Sarah, Barrett, Tristan, Graves, Martin, Eisen, Tim, Mitchell, Thomas J, Warren, Anne, Brindle, Kevin, Sala, Evis, Stewart, Grant, Gallagher, Ferdia, Ursprung, Stephan [0000-0003-2476-178X], McLean, Mary [0000-0002-3752-0179], Priest, Andrew N [0000-0002-9771-4290], Gill, Andrew [0000-0002-9287-9563], Beer, Lucian [0000-0003-4388-7580], Deen, Surrin S [0000-0002-6206-7337], Riemer, Frank [0000-0002-3805-5221], Kaggie, Joshua [0000-0001-6706-3442], Zaccagna, Fulvio [0000-0001-6838-9532], Frary, Amy [0000-0002-4373-3517], Welsh, Sarah [0000-0001-5690-2677], Barrett, Tristan [0000-0002-1180-1474], Graves, Martin [0000-0003-4327-3052], Eisen, Tim [0000-0001-9663-4873], Warren, Anne [0000-0002-1170-7867], Brindle, Kevin [0000-0003-3883-6287], Sala, Evis [0000-0002-5518-9360], Stewart, Grant [0000-0003-3188-9140], Gallagher, Ferdia [0000-0003-4784-5230], Apollo - University of Cambridge Repository, Ursprung S., Woitek R., McLean M.A., Priest A.N., Crispin-Ortuzar M., Brodie C.R., Gill A.B., Gehrung M., Beer L., Riddick A.C.P., Field-Rayner J., Grist J.T., Deen S.S., Riemer F., Kaggie J.D., Zaccagna F., Duarte J.A.G., Locke M.J., Frary A., Aho T.F., Armitage J.N., Casey R., Mendichovszky I.A., Welsh S.J., Barrett T., Graves M.J., Eisen T., Mitchell T.J., Warren A.Y., Brindle K.M., Sala E., Stewart G.D., Gallagher F.A., Gill, Andrew B [0000-0002-9287-9563], Kaggie, Joshua D [0000-0001-6706-3442], Welsh, Sarah J [0000-0001-5690-2677], Brindle, Kevin M [0000-0003-3883-6287], Stewart, Grant D [0000-0003-3188-9140], and Gallagher, Ferdia A [0000-0003-4784-5230]

Subjects
Cancer Research, renal cell carcinoma, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, cancer metabolism, monocarboxylate transporter, Article, Hyperpolarized, hyperpolarized 13C magnetic resonance imaging, Oncology, C magnetic resonance imaging, RC254-282
Abstract

Simple Summary We evaluated renal cancer with varying aggressive appearances on histology, using an emerging form of non-invasive metabolic MRI. This imaging technique assesses the uptake and metabolism of a breakdown product of glucose (pyruvate) labelled with hyperpolarized carbon-13. We show that pyruvate metabolism is dependent on the aggressiveness of an individual tumor and we provide a mechanism for this finding from tissue analysis of molecules influencing pyruvate metabolism, suggesting a role for its membrane transporter. Abstract Differentiating aggressive clear cell renal cell carcinoma (ccRCC) from indolent lesions is challenging using conventional imaging. This work prospectively compared the metabolic imaging phenotype of renal tumors using carbon-13 MRI following injection of hyperpolarized [1-13C]pyruvate (HP-13C-MRI) and validated these findings with histopathology. Nine patients with treatment-naïve renal tumors (6 ccRCCs, 1 liposarcoma, 1 pheochromocytoma, 1 oncocytoma) underwent pre-operative HP-13C-MRI and conventional proton (1H) MRI. Multi-regional tissue samples were collected using patient-specific 3D-printed tumor molds for spatial registration between imaging and molecular analysis. The apparent exchange rate constant (kPL) between 13C-pyruvate and 13C-lactate was calculated. Immunohistochemistry for the pyruvate transporter (MCT1) from 44 multi-regional samples, as well as associations between MCT1 expression and outcome in the TCGA-KIRC dataset, were investigated. Increasing kPL in ccRCC was correlated with increasing overall tumor grade (ρ = 0.92, p = 0.009) and MCT1 expression (r = 0.89, p = 0.016), with similar results acquired from the multi-regional analysis. Conventional 1H-MRI parameters did not discriminate tumor grades. The correlation between MCT1 and ccRCC grade was confirmed within a TCGA dataset (p < 0.001), where MCT1 expression was a predictor of overall and disease-free survival. In conclusion, metabolic imaging using HP-13C-MRI differentiates tumor aggressiveness in ccRCC and correlates with the expression of MCT1, a predictor of survival. HP-13C-MRI may non-invasively characterize metabolic phenotypes within renal cancer.

Published
2022

27. Multiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma

Author

Ferdia A. Gallagher, Wendi Qian, Fulvio Zaccagna, Stephan Ursprung, Grant D. Stewart, Anne Y. Warren, Sarah J. Welsh, Tristan Barrett, Timothy Eisen, Andrew N. Priest, Andrea Machin, Ursprung, Stephan [0000-0003-2476-178X], Priest, Andrew N. [0000-0002-9771-4290], Warren, Anne Y. [0000-0002-1170-7867], Apollo - University of Cambridge Repository, Priest, Andrew N [0000-0002-9771-4290], Stewart, Grant [0000-0003-3188-9140], Warren, Anne [0000-0002-1170-7867], Eisen, Tim [0000-0001-9663-4873], Welsh, Sarah [0000-0001-5690-2677], Gallagher, Ferdia [0000-0003-4784-5230], Barrett, Tristan [0000-0002-1180-1474], Ursprung S., Priest A.N., Zaccagna F., Qian W., Machin A., Stewart G.D., Warren A.Y., Eisen T., Welsh S.J., Gallagher F.A., Barrett T., and Warren, Anne Y [0000-0002-1170-7867]

Subjects
Male, medicine.medical_treatment, Cancer Treatment, urologic and male genital diseases, Nephrectomy, Metastasis, Diagnostic Radiology, Renal cell carcinoma, Basic Cancer Research, Medicine and Health Sciences, Sunitinib, ComputingMilieux_MISCELLANEOUS, Brain Mapping, Multidisciplinary, medicine.diagnostic_test, Radiology and Imaging, Middle Aged, Magnetic Resonance Imaging, Kidney Neoplasms, Neoadjuvant Therapy, Treatment Outcome, Oncology, Nephrology, Renal Cancer, Medicine, Female, Perfusion, medicine.drug, MRI, Research Article, medicine.medical_specialty, Imaging Techniques, Brain Morphometry, Science, Urology, Surgical and Invasive Medical Procedures, Neuroimaging, Antineoplastic Agents, Research and Analysis Methods, Urinary System Procedures, Diagnostic Medicine, medicine, Humans, Multiparametric Magnetic Resonance Imaging, Carcinoma, Renal Cell, Aged, Surgical Excision, business.industry, Diffusion Weighted Imaging, Carcinoma, Renal Cell Carcinoma, Cancer, Cancers and Neoplasms, Biology and Life Sciences, Magnetic resonance imaging, medicine.disease, Clinical trial, Genitourinary Tract Tumors, business, Neuroscience
Abstract

Funder: NIHR Cambridge Biomedical Research Centre, Funder: Addenbrooke’s Charitable Trust, Funder: National Institute for Health Research (NIHR), Funder: Mark Foundation For Cancer Research, Funder: Cambridge Commonwealth, European and International Trust, Funder: Cancer Research UK, Funder: Cambridge Clinical Trials Unit, Funder: Cancer Research UK Cambridge Centre, Funder: Engineering and Physical Sciences Research Council Cancer Imaging Centre in Cambridge and Manchester, Funder: Cambridge Experimental Cancer Medicine Centre, PURPOSE: To detect early response to sunitinib treatment in metastatic clear cell renal cancer (mRCC) using multiparametric MRI. METHOD: Participants with mRCC undergoing pre-surgical sunitinib therapy in the prospective NeoSun clinical trial (EudraCtNo: 2005-004502-82) were imaged before starting treatment, and after 12 days of sunitinib therapy using morphological MRI sequences, advanced diffusion-weighted imaging, measurements of R2* (related to hypoxia) and dynamic contrast-enhanced imaging. Following nephrectomy, participants continued treatment and were followed-up with contrast-enhanced CT. Changes in imaging parameters before and after sunitinib were assessed with the non-parametric Wilcoxon signed-rank test and the log-rank test was used to assess effects on survival. RESULTS: 12 participants fulfilled the inclusion criteria. After 12 days, the solid and necrotic tumor volumes decreased by 28% and 17%, respectively (p = 0.04). However, tumor-volume reduction did not correlate with progression-free or overall survival (PFS/OS). Sunitinib therapy resulted in a reduction in median solid tumor diffusivity D from 1298x10-6 to 1200x10-6mm2/s (p = 0.03); a larger decrease was associated with a better RECIST response (p = 0.02) and longer PFS (p = 0.03) on the log-rank test. An increase in R2* from 19 to 28s-1 (p = 0.001) was observed, paralleled by a decrease in Ktrans from 0.415 to 0.305min-1 (p = 0.01) and a decrease in perfusion fraction from 0.34 to 0.19 (p

Published
2022
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