المؤلفون: Kang, Eun‐Young, Weir, Ashley, Meagher, Nicola S, Farrington, Kyo, Nelson, Gregg S, Ghatage, Prafull, Lee, Cheng‐Han, Riggan, Marjorie J, Bolithon, Adelyn, Popovic, Gordana, Leung, Betty, Tang, Katrina, Lambie, Neil, Millstein, Joshua, Alsop, Jennifer, Anglesio, Michael S, Ataseven, Beyhan, Barlow, Ellen, Beckmann, Matthias W, Berger, Jessica, Bisinotto, Christiani, Bösmüller, Hans, Boros, Jessica, Brand, Alison H, Brooks‐Wilson, Angela, Brucker, Sara Y, Carney, Michael E, Casablanca, Yovanni, Cazorla‐Jiménez, Alicia, Cohen, Paul A, Conrads, Thomas P, Cook, Linda S, Coulson, Penny, Courtney‐Brooks, Madeleine, Cramer, Daniel W, Crowe, Philip, Cunningham, Julie M, Cybulski, Cezary, Darcy, Kathleen M, El‐Bahrawy, Mona A, Elishaev, Esther, Erber, Ramona, Farrell, Rhonda, Fereday, Sian, Fischer, Anna, García, María J, Gayther, Simon A, Gentry‐Maharaj, Aleksandra, Gilks, C Blake, Group, AOCS, Grube, Marcel, Harnett, Paul R, Harrington, Shariska Petersen, Harter, Philipp, Hartmann, Arndt, Hecht, Jonathan L, Heikaus, Sebastian, Hein, Alexander, Heitz, Florian, Hendley, Joy, Hernandez, Brenda Y, Polo, Susanna Hernando, Heublein, Sabine, Hirasawa, Akira, Høgdall, Estrid, Høgdall, Claus K, Horlings, Hugo M, Huntsman, David G, Huzarski, Tomasz, Jewell, Andrea, Jimenez‐Linan, Mercedes, Jones, Michael E, Kaufmann, Scott H, Kennedy, Catherine J, Khabele, Dineo, Kommoss, Felix KF, Kruitwagen, Roy FPM, Lambrechts, Diether, Le, Nhu D, Lener, Marcin, Lester, Jenny, Leung, Yee, Linder, Anna, Loverix, Liselore, Lubiński, Jan, Madan, Rashna, Maxwell, G Larry, Modugno, Francesmary, Neuhausen, Susan L, Olawaiye, Alexander, Olbrecht, Siel, Orsulic, Sandra, Palacios, José, Pearce, Celeste Leigh, Pike, Malcolm C, Quinn, Carmel M, Mohan, Ganendra Raj, Rodríguez‐Antona, Cristina, Ruebner, Matthias, Ryan, Andy

المصدر: Cancer. 129(5)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Clinical Research, Ovarian Cancer, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Female, Humans, Ovarian Neoplasms, Transcription Factors, Carcinoma, RNA, Messenger, Cystadenocarcinoma, Serous, Oncogene Proteins, Cyclin E, CCNE1 amplification, cyclin E1 expression, high-grade serous carcinoma, ovarian cancer, prognosis, AOCS Group, Public Health and Health Services, Oncology & Carcinogenesis, Oncology and carcinogenesis, Public health

الوصف: BackgroundCyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC.MethodsWithin the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated.ResultsHigh-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss.ConclusionThis study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/6cm6k1w1Test

المؤلفون: 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, Köbel, Martin

المصدر: The journal of pathology. Clinical research. 4(4)

مصطلحات موضوعية: 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

الوصف: 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.

الوصول الحر: https://escholarship.org/uc/item/2k43648vTest

المؤلفون: Kang, Eun-Young, Weir, Ashley, Meagher, Nicola S., Farrington, Kyo, Nelson, Gregg S., Ghatage, Prafull, Lee, Cheng-Han, Riggan, Marjorie J., Bolithon, Adelyn, Popovic, Gordana, Leung, Betty, Tang, Katrina, Lambie, Neil, Millstein, Joshua, Alsop, Jennifer, Anglesio, Michael S., Ataseven, Beyhan, Barlow, Ellen, Beckmann, Matthias W., Berger, Jessica, Bisinotto, Christiani, Boesmueller, Hans, Boros, Jessica, Brand, Alison H., Brooks-Wilson, Angela, Brucker, Sara Y., Carney, Michael E., Casablanca, Yovanni, Cazorla-Jimenez, Alicia, Cohen, Paul A., Conrads, Thomas P., Cook, Linda S., Coulson, Penny, Courtney-Brooks, Madeleine, Cramer, Daniel W., Crowe, Philip, Cunningham, Julie M., Cybulski, Cezary, Darcy, Kathleen M., El-Bahrawy, Mona A., Elishaev, Esther, Erber, Ramona, Farrell, Rhonda, Fereday, Sian, Fischer, Anna, Garcia, Maria J., Gayther, Simon A., Gentry-Maharaj, Aleksandra, Gilks, C. Blake, Grube, Marcel, Harnett, Paul R., Harrington, Shariska Petersen, Harter, Philipp, Hartmann, Arndt, Hecht, Jonathan L., Heikaus, Sebastian, Hein, Alexander, Heitz, Florian, Hendley, Joy, Hernandez, Brenda Y., Hernando Polo, Susanna, Heublein, Sabine, Hirasawa, Akira, Hogdall, Estrid, Hogdall, Claus K., Horlings, Hugo M., Huntsman, David G., Huzarski, Tomasz, Jewell, Andrea, Jimenez-Linan, Mercedes, Jones, Michael E., Kaufmann, Scott H., Kennedy, Catherine J., Khabele, Dineo, Kommoss, Felix K.F., Kruitwagen, Roy F.P.M., Lambrechts, Diether, Le, Nhu D., Lener, Marcin, Lester, Jenny, Leung, Yee, Linder, Anna, Loverix, Liselore, Lubinski, Jan, Madan, Rashna, Maxwell, G. Larry, Modugno, Francesmary, Neuhausen, Susan L., Olawaiye, Alexander, Olbrecht, Siel, Orsulic, Sandra, Palacios, Jose, Pearce, Celeste Leigh, Pike, Malcolm C., Quinn, Carmel M., Mohan, Ganendra Raj, Rodriguez-Antona, Cristina, Ruebner, Matthias, Ryan, Andy, Salfinger, Stuart G., Sasamoto, Naoko, Schildkraut, Joellen M., Schoemaker, Minouk J., Shah, Mitul, Sharma, Raghwa, Shvetsov, Yurii B., Singh, Naveena, Sonke, Gabe S., Steele, Linda, Stewart, Colin J.R., Sundfeldt, Karin, Swerdlow, Anthony J., Talhouk, Aline, Tan, Adeline, Taylor, Sarah E., Terry, Kathryn L., Toloczko, Aleksandra, Traficante, Nadia, Van de Vijver, Koen, van der Aa, Maaike A., Van Gorp, Toon, Van Nieuwenhuysen, Els, Van-Wagensveld, Lilian, Vergote, Ignace, Vierkant, Robert A., Wang, Chen, Wilkens, Lynne R., Winham, Stacey J., Wu, Anna H., Benitez, Javier, Berchuck, Andrew, Candido Dos Reis, Francisco J., DeFazio, Anna, Fasching, Peter A., Goode, Ellen L., Goodman, Marc T., Gronwald, Jacek, Karlan, Beth Y., Kommoss, Stefan, Menon, Usha, Sinn, Hans-Peter, Staebler, Annette, Brenton, James D., Bowtell, David D., Pharoah, Paul D.P., Ramus, Susan J., Kobel, Martin

المساهمون: AOCS Group

المصدر: 0008-543X ; Cancer: interdisciplinary international journal of the American Cancer Society

مصطلحات موضوعية: Human medicine

الوصف: Background: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. Methods: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. Results: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. Conclusion: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.

العلاقة: info:eu-repo/semantics/altIdentifier/isi/000927885700001

الإتاحة: https://doi.org/10.1002/CNCR.34582Test
https://hdl.handle.net/10067/1953550151162165141Test
https://repository.uantwerpen.be/docstore/d:irua:16967Test

المؤلفون: Kang, Eun-Young, Weir, Ashley, Meagher, Nicola S, Farrington, Kyo, Nelson, Gregg S, Ghatage, Prafull, Lee, Cheng-Han, Riggan, Marjorie J, Bolithon, Adelyn, Popovic, Gordana, Leung, Betty, Tang, Katrina, Lambie, Neil, Millstein, Joshua, Alsop, Jennifer, Anglesio, Michael S, Ataseven, Beyhan, Barlow, Ellen, Beckmann, Matthias W, Berger, Jessica, Bisinotto, Christiani, Bösmüller, Hans, Boros, Jessica, Brand, Alison H, Brooks-Wilson, Angela, Brucker, Sara Y, Carney, Michael E, Casablanca, Yovanni, Cazorla-Jiménez, Alicia, Cohen, Paul A, Conrads, Thomas P, Cook, Linda S, Coulson, Penny, Courtney-Brooks, Madeleine, Cramer, Daniel W, Crowe, Philip, Cunningham, Julie M, Cybulski, Cezary, Darcy, Kathleen M, El-Bahrawy, Mona A, Elishaev, Esther, Erber, Ramona, Farrell, Rhonda, Fereday, Sian, Fischer, Anna, García, María J, Gayther, Simon A, Gentry-Maharaj, Aleksandra, Gilks, C Blake, AOCS Group, Grube, Marcel, Harnett, Paul R, Harrington, Shariska Petersen, Harter, Philipp, Hartmann, Arndt, Hecht, Jonathan L, Heikaus, Sebastian, Hein, Alexander, Heitz, Florian, Hendley, Joy, Hernandez, Brenda Y, Polo, Susanna Hernando, Heublein, Sabine, Hirasawa, Akira, Høgdall, Estrid, Høgdall, Claus K, Horlings, Hugo M, Huntsman, David G, Huzarski, Tomasz, Jewell, Andrea, Jimenez-Linan, Mercedes, Jones, Michael E, Kaufmann, Scott H, Kennedy, Catherine J, Khabele, Dineo, Kommoss, Felix KF, Kruitwagen, Roy FPM, Lambrechts, Diether, Le, Nhu D, Lener, Marcin, Lester, Jenny, Leung, Yee, Linder, Anna, Loverix, Liselore, Lubiński, Jan, Madan, Rashna, Maxwell, G Larry, Modugno, Francesmary, Neuhausen, Susan L, Olawaiye, Alexander, Olbrecht, Siel, Orsulic, Sandra, Palacios, José, Pearce, Celeste Leigh, Pike, Malcolm C, Quinn, Carmel M, Mohan, Ganendra Raj, Rodríguez-Antona, Cristina, Ruebner, Matthias, Ryan, Andy, Salfinger, Stuart G, Sasamoto, Naoko, Schildkraut, Joellen M, Schoemaker, Minouk J, Shah, Mitul, Sharma, Raghwa, Shvetsov, Yurii B, Singh, Naveena, Sonke, Gabe S, Steele, Linda, Stewart, Colin JR, Sundfeldt, Karin, Swerdlow, Anthony J, Talhouk, Aline, Tan, Adeline, Taylor, Sarah E, Terry, Kathryn L, Tołoczko, Aleksandra, Traficante, Nadia, Van de Vijver, Koen K, van der Aa, Maaike A, Van Gorp, Toon, Van Nieuwenhuysen, Els, van-Wagensveld, Lilian, Vergote, Ignace, Vierkant, Robert A, Wang, Chen, Wilkens, Lynne R, Winham, Stacey J, Wu, Anna H, Benitez, Javier, Berchuck, Andrew, Candido Dos Reis, Francisco J, DeFazio, Anna, Fasching, Peter A, Goode, Ellen L, Goodman, Marc T, Gronwald, Jacek, Karlan, Beth Y, Kommoss, Stefan, Menon, Usha, Sinn, Hans-Peter, Staebler, Annette, Brenton, James D, Bowtell, David D, Pharoah, Paul DP, Ramus, Susan J, Köbel, Martin

المصدر: Cancer , 129 (5) pp. 697-713. (2022)

مصطلحات موضوعية: CCNE1 amplification, cyclin E1 expression, high-grade serous carcinoma, ovarian cancer, prognosis

الوصف: BACKGROUND: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. METHODS: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. RESULTS: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. CONCLUSION: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.

وصف الملف: text

العلاقة: https://discovery.ucl.ac.uk/id/eprint/10164476/1/CCNE1%20and%20survival%20of%20patients%20with%20tubo%20ovarian%20high%20grade%20serous%20carcinoma.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10164476Test/

الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10164476/1/CCNE1%20and%20survival%20of%20patients%20with%20tubo%20ovarian%20high%20grade%20serous%20carcinoma.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10164476Test/

المؤلفون: Kang, Eun‐Young, Weir, Ashley, Meagher, Nicola S., Farrington, Kyo, Nelson, Gregg S., Ghatage, Prafull, Lee, Cheng‐Han, Riggan, Marjorie J., Bolithon, Adelyn, Popovic, Gordana, Leung, Betty, Tang, Katrina, Lambie, Neil, Millstein, Joshua, Alsop, Jennifer, Anglesio, Michael S., Ataseven, Beyhan, Barlow, Ellen, Beckmann, Matthias W., Berger, Jessica, Bisinotto, Christiani, Bösmüller, Hans, Boros, Jessica, Brand, Alison H., Brooks‐Wilson, Angela, Brucker, Sara Y., Carney, Michael E., Casablanca, Yovanni, Cazorla‐Jiménez, Alicia, Cohen, Paul A., Conrads, Thomas P., Cook, Linda S., Coulson, Penny, Courtney‐Brooks, Madeleine, Cramer, Daniel W., Crowe, Philip, Cunningham, Julie M., Cybulski, Cezary, Darcy, Kathleen M., El‐Bahrawy, Mona A., Elishaev, Esther, Erber, Ramona, Farrell, Rhonda, Fereday, Sian, Fischer, Anna, García, María J., Gayther, Simon A., Gentry‐Maharaj, Aleksandra, Gilks, C. Blake, Grube, Marcel

المساهمون: National Cancer Institute, Alberta Precision Laboratories

المصدر: Cancer ; volume 129, issue 5, page 697-713 ; ISSN 0008-543X 1097-0142

الوصف: Background Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo‐ovarian high‐grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large‐scale, histotype‐specific validation has been performed. The hypothesis was that high‐level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. Methods Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. Results High‐level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high‐level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08‐1.47, p = .034, and HR, 1.18; 95% CI, 1.05‐1.32, p = .015, respectively). This was also true for cases with combined high‐level amplification/overexpression (HR, 1.26; 95% CI, 1.09‐1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1‐SD increase; 95% CI, 0.94‐1.06; p = .58). CCNE1 high‐level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. Conclusion This study provides large‐scale validation that CCNE1 high‐level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.

الإتاحة: https://doi.org/10.1002/cncr.34582Test

المؤلفون: 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

المصدر: Rambau , P F , Vierkant , R A , Intermaggio , M P , Kelemen , L E , Goodman , M T , Herpel , E , Pharoah , P D , Kommoss , S , Jimenez-Linan , M , Karlan , B Y , Gentry-Maharaj , A , Menon , U , Polo , S H , Candido Dos Reis , F J , Doherty , J A , Gayther , S A , Sharma , R , Larson , M C , Harnett , P R , Hatfield , E , De Andrade , J ....

وصف الملف: application/pdf

الإتاحة: https://doi.org/10.1002/cjp2.2018.4.issue-4Test
https://curis.ku.dk/portal/da/publications/association-of-p16-expression-with-prognosis-varies-across-ovarian-carcinoma-histotypesTest(655fb6c3-2114-4fbc-9610-c6c64a0abb48).html
https://curis.ku.dk/ws/files/218513942/Rambau_et_al_2018_The_Journal_of_Pathology_Clinical_Research.pdfTest

المؤلفون: Kamieniak, Marta M., Muñoz-Repeto, Iván, Rico, Daniel, Osório, Ana, Urioste, Miguel, García-Donas, Jesús, Hernando, Susana, Robles-Díaz, Luis, Ramón y Cajal, Teresa, Cazorla Jiménez, Alicia, Sáez, Raquel Salazar, García-Bueno, José María, Domingo, Samuel, Borrego, Salud A., Palacios, José Luis, Van De Wiel, Mark A., Ylstra, Bauke, Benítez, Javier, García, María José G

المساهمون: UAM. Departamento de Anatomía Patológica, UAM. Departamento de Medicina Preventiva y Salud Pública y Microbiología

مصطلحات موضوعية: Ovarian cancer, Hereditary, BRCA1, BRCA2, Genomic alteration, Medicina

الوصف: Background: Few studies have attempted to characterise genomic changes occurring in hereditary epithelial ovarian carcinomas (EOCs) and inconsistent results have been obtained. Given the relevance of DNA copy number alterations in ovarian oncogenesis and growing clinical implications of the BRCA-gene status, we aimed to characterise the genomic profiles of hereditary and sporadic ovarian tumours. Methods: High-resolution array Comparative Genomic Hybridisation profiling of 53 familial (21 BRCA1, 6 BRCA2 and 26 non- BRCA1/2) and 15 sporadic tumours in combination with supervised and unsupervised analysis was used to define common and/or specific copy number features. Results: Unsupervised hierarchical clustering did not stratify tumours according to their familial or sporadic condition or to their BRCA1/2 mutation status. Common recurrent changes, spanning genes potentially fundamental for ovarian carcinogenesis, regardless of BRCA mutations, and several candidate subtype-specific events were defined. Despite similarities, greater contribution of losses was revealed to be a hallmark of BRCA1 and BRCA2 tumours. Conclusion: Somatic alterations occurring in the development of familial EOCs do not differ substantially from the ones occurring in sporadic carcinomas. However, some specific features like extensive genomic loss observed in BRCA1/2 tumours may be of clinical relevance helping to identify BRCA-related patients likely to respond to PARP inhibitors ; This study was funded by the Fondo de Investigacio´n Sanitaria (FIS), Instituto de Salud Carlos III (grants CP07/00113 and PS09/01094)

وصف الملف: application/pdf

العلاقة: British Journal of Cancer; British Journal of Cancer 108.8 (2013): 1732-1742; 0007-0920 (print); 1532-1827 (online); http://hdl.handle.net/10486/663027Test; 1732; 1742; 108

الإتاحة: https://doi.org/10.1038/bjc.2013.141Test
http://hdl.handle.net/10486/663027Test

المؤلفون: Gayarre, Javier, Kamieniak, Marta M., Cazorla-Jiménez, Alicia, Muñoz-Repeto, Ivan, Borrego, Salud, García Donas, J, Hernando, Susana, Robles-Díaz, Luis, García-Bueno, José María, Ramon y Cajal, Teresa, Hernández-Agudo, Elena, Heredia Soto, Victoria, Márquez-Rodas, Ivan, Echarri, María José, Lacambra-Calvet, Carmen, Sáez, Raquel, Cusidó, Maite, Redondo, Andrés, Paz-Ares, Luis, Hardisson, David, Mendiola, Marta, Palacios, José, Benitez, Javier, Garcia, Maria José, Universitat Autònoma de Barcelona. Departament de Medicina

مصطلحات موضوعية: Cisplatin-Sensitivity, DNA Repair, GTF2H5, Ovarian Epithelial Cancer, Survival, 6q24-26 Deletion

الوصف: We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients. In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays. Upon stratification of cases into high- and low-GTF2H5 staining categories (> and ≤ median staining, respectively) Kaplan-Meier and log-rank test were used to estimate patients' survival and assess statistical differences. We also evaluated the association of GTF2H5 with survival at the transcriptional level by using the on-line Kaplan-Meier plotter tool, which includes gene expression and survival data of 855 high-grade serous ovarian cancer patients from 13 different datasets. Finally, we determined whether stable short hairpin RNA-mediated GTF2H5 downregulation modulates cisplatin sensitivity in the SKOV3 and COV504 cell lines by using cytotoxicity assays. Low expression of GTF2H5 was associated with longer 5-year survival of patients at the protein (hazard ratio [HR], 0.52; 95% CI, 0.29 to 0.93; p=0.024) and transcriptional level (HR, 0.80; 95% CI, 0.65 to 0.97; p=0.023) in high-grade serous ovarian cancer patients. We confirmed the association with 5-year overall survival (HR, 0.55; 95% CI, 0.38 to 0.78; p=0.0007) and also found an association with progression-free survival (HR, 0.72; 95% CI, 0.54 to 0.96; p=0.026) in a homogenous group of 388 high-stage (stages III-IV using the International Federation of Gynecology and Obstetrics staging system), optimally debulked high-grade serous ovarian cancer patients. GTF2H5- silencing induced a decrease of the half maximal inhibitory concentration upon cisplatin treatment in GTF2H5 -silenced ovarian cancer cells. Low levels of GTF2H5 are associated with enhanced prognosis in high-grade serous ...

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العلاقة: Journal of Gynecologic Oncology; Vol. 27 (november 2015); https://ddd.uab.cat/record/185444Test; urn:10.3802/jgo.2016.27.e7; urn:oai:ddd.uab.cat:185444; urn:pmid:26463438; urn:pmc-uid:4695457; urn:pmcid:PMC4695457; urn:oai:pubmedcentral.nih.gov:4695457

الإتاحة: https://ddd.uab.cat/record/185444Test

المؤلفون: Salido Fernández, Sergio, Tejedor Togores, Patricia, López Rojo, Irene, Cazorla Jiménez, Alicia, Benítez Dupin, Olivia, Rivas Fidalgo, Sonia, Gómez Ramírez, Joaquín, Díaz-Miguel Maseda, Mariano

المصدر: Revista de Senología y Patología Mamaria ; volume 28, issue 3, page 113-119 ; ISSN 0214-1582

مصطلحات موضوعية: Radiology, Nuclear Medicine and imaging, Oncology, Obstetrics and Gynecology, Surgery

الإتاحة: https://doi.org/10.1016/j.senol.2015.04.004Test
https://api.elsevier.com/content/article/PII:S0214158215000651?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0214158215000651?httpAccept=text/plainTest

العنوان البديل: Neuroendocrine breast carcinoma with pulmonary differentiation. A case report. (English)

المؤلفون: Marcos-Santos, Cristina, Albi-Martin, Beatriz, Peña y Lillo-Rodríguez, Andrea, Cazorla-Jiménez, Alicia

المصدر: Ginecología y Obstetricia de México; jun2019, Vol. 87 Issue 6, p397-404, 8p

مصطلحات موضوعية: BREAST cancer, NEUROENDOCRINE tumors, TUMORS, METASTASIS, CANCER cells

الملخص (بالإنجليزية): BACKGROUND: Neuroendocrine carcinomas are infrequent breast neoplasms representing less than 2% of breast neoplasms. The diagnosis is difficult, since their clinical and morphological characteristics do not help to differentiate them from other types of breast neoplasms. The immunohistochemistry that will determine the characterization of the tumor by the presence of neuroendocrine markers. It is important to rule out a cases of metastasis related to a different primary origin, in order to prescribe the appropriate treatment for the patient. CLINICAL CASE: A 37-year-old patient from another institution with a diagnosis suggestive of high-grade carcinoma of medium cells, with neuroendocrine differentiation, involvement of the 3 levels of Berg and pathological supraclavicular adenopathies. After performing the imaging studies and determining the specific tumor markers of the disease, the diagnosis of breast neuroendocrine carcinoma. Neoadjuvant treatment with cisplastin and etoposide is indicated, with the same partial reaction of 50%. Subsequently, the radical mastectomy was performed, with the emptying of the 3 levels of Berg and the removal of the supraclavicular nodes without apparent complications. Currently remains stable in the treatment with adjuvant chemotherapy. CONCLUSION: It is important to determine the tumor markers associated with breast neuroendocrine carcinomas, with the aim of establishing accurate diagnosis and implementing the appropriate treatment, which may vary depending on its origin. To date there is no consensus of treatment, so each case must be individualized. Additional studies are required to expand the knowledge of this tumor variant. [ABSTRACT FROM AUTHOR]

Abstract (Spanish): ANTECEDENTES: Los carcinomas neuroendocrinos de mama son neoplasias malignas poco frecuentes, con incidencia de 2%. El diagnóstico es difícil de establecer debido a sus características clínicas y morfológicas inespecíficas. La inmunohistoquímica es un estudio útil para identificar marcadores neuroendocrinos. Es importante descartar los casos de metástasis relacionados con algún origen primario distinto, para de esta forma prescribir el tratamiento adecuado. CASO CLÍNICO: Paciente de 37 años, procedente de otra institución con diagnóstico sugerente de carcinoma de alto grado de células medianas, con diferenciación neuroendocrina, afectación de los tres niveles de Berg y adenopatías supraclaviculares patológicas. Después de los estudios de imagen y determinación de marcadores tumorales específicos de la enfermedad se estableció el diagnóstico de carcinoma neuroendocrino de mama. Se indicó tratamiento neoadyuvante con cisplastino y etoposido, con el que se observó reacción parcial de 50%. Posteriormente se efectuó la mastectomía radical, con vaciamiento de los tres niveles de Berg y extirpación de los ganglios supraclaviculares, sin complicaciones aparentes. En la actualidad, la paciente permanece estable, en tratamiento con quimioterapia coadyuvante. CONCLUSIONES: Lo importante en estos casos es determinar los marcadores tumorales asociados con los carcinomas neuroendocrinos de mama y así poder establecer el diagnóstico certero e implementar el tratamiento adecuado, que puede variar en función de su origen. Hasta la fecha no existe un consenso de tratamiento, por lo que cada caso debe individualizarse. Se requieren estudios adicionales para ampliar el conocimiento de esta variante tumoral. [ABSTRACT FROM AUTHOR]

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