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., ... Köbel, M. (2018). Association of p16 expression with prognosis varies across ovarian carcinoma histotypes: an Ovarian Tumor Tissue Analysis consortium study. The Journal of Pathology: Clinical Research, 4(4), 250-261. https://doi.org/10.1002/cjp2.2018.4.issue-4
Rambau, PF, Vierkant, RA, Intermaggio, MP, Kelemen, LE, Goodman, MT, Herpel, E, Pharoah, PD, Kommoss, S, Jimenez-Linan, M, Karlan, BY, Gentry-Maharaj, A, Menon, U, Polo, SH, Candido Dos Reis, FJ, Doherty, JA, Gayther, SA, Sharma, R, Larson, MC, Harnett, PR, Hatfield, E, De Andrade, JM, Nelson, GS, Steed, H, Schildkraut, JM, Carney, ME, Høgdall, E, Whittemore, AS, Widschwendter, M, Kennedy, CJ, Wang, F, Wang, Q, Wang, C, Armasu, SM, Daley, F, Coulson, P, Jones, ME, Anglesio, MS, Chow, C, De Fazio, A, García-Closas, M, Brucker, SY, Cybulski, C, Harris, HR, Hartkopf, AD, Huzarski, T, Jensen, A, Lubiński, J, Oszurek, O, Benitez, J, Mina, F, Staebler, A, Taran, FA, Pasternak, J, Talhouk, A, Rossing, MA, Hendley, J, AOCS Group, Edwards, RP, Fereday, S, Modugno, F, Ness, RB, Sieh, W, El-Bahrawy, MA, Winham, SJ, Lester, J, Kjaer, SK, Gronwald, J, Sinn, P, Fasching, PA, Chang-Claude, J, Moysich, KB, Bowtell, DD, Hernandez, BY, Luk, H, Behrens, S, Shah, M, Jung, A, Ghatage, P, Alsop, J, Alsop, K, García-Donas, J, Thompson, PJ, Swerdlow, AJ, Karpinskyj, C, Cazorla-Jiménez, A, García, MJ, Deen, S, Wilkens, LR, Palacios, J, Berchuck, A, Koziak, JM, Brenton, JD, Cook, LS, Goode, EL, Huntsman, DG, Ramus, SJ & Köbel, M 2018, 'Association of p16 expression with prognosis varies across ovarian carcinoma histotypes: an Ovarian Tumor Tissue Analysis consortium study', The Journal of Pathology: Clinical Research, bind 4, nr. 4, s. 250-261. https://doi.org/10.1002/cjp2.2018.4.issue-4
@article{655fb6c321144fbc9610c6c64a0abb48,
title = "Association of p16 expression with prognosis varies across ovarian carcinoma histotypes: an Ovarian Tumor Tissue Analysis consortium study",
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.",
author = "Rambau, {Peter F} and Vierkant, {Robert A} and Intermaggio, {Maria P} and Kelemen, {Linda E} and Goodman, {Marc T} and Esther Herpel and Pharoah, {Paul D} and Stefan Kommoss and Mercedes Jimenez-Linan and Karlan, {Beth Y} and Aleksandra Gentry-Maharaj and Usha Menon and Polo, {Susanna Hernando} and {Candido Dos Reis}, {Francisco J} and Doherty, {Jennifer Anne} and Gayther, {Simon A} and Raghwa Sharma and Larson, {Melissa C} and Harnett, {Paul R} and Emma Hatfield and {De Andrade}, {Jurandyr M} and Nelson, {Gregg S} and Helen Steed and Schildkraut, {Joellen M} and Carney, {Micheal E} and Estrid H{\o}gdall and Whittemore, {Alice S} and Martin Widschwendter and Kennedy, {Catherine J} and Frances Wang and Qin Wang and Chen Wang and Armasu, {Sebastian M} and Frances Daley and Penny Coulson and Jones, {Micheal E} and Anglesio, {Micheal S} and Christine Chow and {De Fazio}, Anna and Montserrat Garc{\'i}a-Closas and Brucker, {Sara Y} and Cezary Cybulski and Harris, {Holly R} and Hartkopf, {Andreas D} and Tomasz Huzarski and Allan Jensen and Jan Lubi{\'n}ski and Oleg Oszurek and Javier Benitez and Fady Mina and Annette Staebler and Taran, {Florin Andrei} and Jana Pasternak and Aline Talhouk and Rossing, {Mary Anne} and Joy Hendley and {AOCS Group} and Edwards, {Robert P} and Sian Fereday and Francesmary Modugno and Ness, {Roberta B} and Weiva Sieh and El-Bahrawy, {Mona A} and Winham, {Stacey J} and Jenny Lester and Kjaer, {Susanne K} and Jacek Gronwald and Peter Sinn and Fasching, {Peter A} and Jenny Chang-Claude and Moysich, {Kirsten B} and Bowtell, {David D} and Hernandez, {Brenda Y} and Hugh Luk and Sabine Behrens and Mitul Shah and Audrey Jung and Prafull Ghatage and Jennifer Alsop and Kathryn Alsop and Jes{\'u}s Garc{\'i}a-Donas and Thompson, {Pamela J} and Swerdlow, {Anthony J} and Chloe Karpinskyj and Alicia Cazorla-Jim{\'e}nez and Garc{\'i}a, {Mar{\'i}a J} and Susha Deen and Wilkens, {Lynne R} and Jos{\'e} Palacios and Andrew Berchuck and Koziak, {Jennifer M} and Brenton, {James D} and Cook, {Linda S} and Goode, {Ellen L} and Huntsman, {David G} and Ramus, {Susan J} and Martin K{\"o}bel",
year = "2018",
month = oct,
day = "1",
doi = "10.1002/cjp2.2018.4.issue-4",
language = "English",
volume = "4",
pages = "250--261",
journal = "The Journal of Pathology: Clinical Research",
issn = "2056-4538",
publisher = "JohnWiley & Sons Ltd",
number = "4",
}
TY - JOUR
T1 - Association of p16 expression with prognosis varies across ovarian carcinoma histotypes
T2 - an Ovarian Tumor Tissue Analysis consortium study
AU - Rambau, Peter F
AU - Vierkant, Robert A
AU - Intermaggio, Maria P
AU - Kelemen, Linda E
AU - Goodman, Marc T
AU - Herpel, Esther
AU - Pharoah, Paul D
AU - Kommoss, Stefan
AU - Jimenez-Linan, Mercedes
AU - Karlan, Beth Y
AU - Gentry-Maharaj, Aleksandra
AU - Menon, Usha
AU - Polo, Susanna Hernando
AU - Candido Dos Reis, Francisco J
AU - Doherty, Jennifer Anne
AU - Gayther, Simon A
AU - Sharma, Raghwa
AU - Larson, Melissa C
AU - Harnett, Paul R
AU - Hatfield, Emma
AU - De Andrade, Jurandyr M
AU - Nelson, Gregg S
AU - Steed, Helen
AU - Schildkraut, Joellen M
AU - Carney, Micheal E
AU - Høgdall, Estrid
AU - Whittemore, Alice S
AU - Widschwendter, Martin
AU - Kennedy, Catherine J
AU - Wang, Frances
AU - Wang, Qin
AU - Wang, Chen
AU - Armasu, Sebastian M
AU - Daley, Frances
AU - Coulson, Penny
AU - Jones, Micheal E
AU - Anglesio, Micheal S
AU - Chow, Christine
AU - De Fazio, Anna
AU - García-Closas, Montserrat
AU - Brucker, Sara Y
AU - Cybulski, Cezary
AU - Harris, Holly R
AU - Hartkopf, Andreas D
AU - Huzarski, Tomasz
AU - Jensen, Allan
AU - Lubiński, Jan
AU - Oszurek, Oleg
AU - Benitez, Javier
AU - Mina, Fady
AU - Staebler, Annette
AU - Taran, Florin Andrei
AU - Pasternak, Jana
AU - Talhouk, Aline
AU - Rossing, Mary Anne
AU - Hendley, Joy
AU - AOCS Group
AU - Edwards, Robert P
AU - Fereday, Sian
AU - Modugno, Francesmary
AU - Ness, Roberta B
AU - Sieh, Weiva
AU - El-Bahrawy, Mona A
AU - Winham, Stacey J
AU - Lester, Jenny
AU - Kjaer, Susanne K
AU - Gronwald, Jacek
AU - Sinn, Peter
AU - Fasching, Peter A
AU - Chang-Claude, Jenny
AU - Moysich, Kirsten B
AU - Bowtell, David D
AU - Hernandez, Brenda Y
AU - Luk, Hugh
AU - Behrens, Sabine
AU - Shah, Mitul
AU - Jung, Audrey
AU - Ghatage, Prafull
AU - Alsop, Jennifer
AU - Alsop, Kathryn
AU - García-Donas, Jesús
AU - Thompson, Pamela J
AU - Swerdlow, Anthony J
AU - Karpinskyj, Chloe
AU - Cazorla-Jiménez, Alicia
AU - García, María J
AU - Deen, Susha
AU - Wilkens, Lynne R
AU - Palacios, José
AU - Berchuck, Andrew
AU - Koziak, Jennifer M
AU - Brenton, James D
AU - Cook, Linda S
AU - Goode, Ellen L
AU - Huntsman, David G
AU - Ramus, Susan J
AU - Köbel, Martin
PY - 2018/10/1
Y1 - 2018/10/1
N2 - 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.
AB - 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.
U2 - 10.1002/cjp2.2018.4.issue-4
DO - 10.1002/cjp2.2018.4.issue-4
M3 - Journal article
SN - 2056-4538
VL - 4
SP - 250
EP - 261
JO - The Journal of Pathology: Clinical Research
JF - The Journal of Pathology: Clinical Research
IS - 4
ER -