Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium

Filipe Correia Martins; Dominique Laurent Couturier; Anna Paterson; Anthony N. Karnezis; Christine Chow; Tayyebeh M. Nazeran; Adekunle Odunsi; Aleksandra Gentry-Maharaj; Aleksandra Vrvilo; Alexander Hein; Aline Talhouk; Ana Osorio; Andreas D. Hartkopf; Angela Brooks-Wilson; Anna DeFazio; Anna Fischer; Arndt Hartmann; Brenda Y. Hernandez; Bryan M. McCauley; Chloe Karpinskyj; Christiani B. de Sousa; Claus Høgdall; Daniel G. Tiezzi; Esther Herpel; Florin Andrei Taran; Francesmary Modugno; Gary Keeney; Gregg Nelson; Helen Steed; Honglin Song; Hugh Luk; Javier Benitez; Jennifer Alsop; Jennifer M. Koziak; Jenny Lester; Joseph H. Rothstein; Jurandyr M. de Andrade; Lene Lundvall; Luis Paz-Ares; Luis Robles-Díaz; Lynne R. Wilkens; Maria J. Garcia; Maria P. Intermaggio; Marie Lyne Alcaraz; Mary A. Brett; Matthias W. Beckmann; Mercedes Jimenez-Linan; Michael Anglesio; Michael E. Carney; Michael Schneider; Nadia Traficante; Nadja Pejovic; Naveena Singh; Nhu Le; Peter Sinn; Prafull Ghatage; Ramona Erber; Robert Edwards; Robert Vierkant; Roberta B. Ness; Samuel Leung; Sandra Orsulic; Sara Y. Brucker; Scott H. Kaufmann; Sian Fereday; Simon Gayther; Stacey J. Winham; Stefan Kommoss; Tanja Pejovic; Teri A. Longacre; Valerie McGuire; Valerie Rhenius; Weiva Sieh; Yurii B. Shvetsov; Alice S. Whittemore; Annette Staebler; Beth Y. Karlan; Cristina Rodriguez-Antona; David D. Bowtell; Ellen L. Goode; Estrid Høgdall; Francisco J. Candido dos Reis; Jacek Gronwald; Jenny Chang-Claude; Kirsten B. Moysich; Linda E. Kelemen; Linda S. Cook; Marc T. Goodman; Peter A. Fasching; Robin Crawford; Suha Deen; Usha Menon; David G. Huntsman; Martin Köbel; Susan J. Ramus; Paul D.P. Pharoah; James D. Brenton

doi:10.1038/s41416-020-0900-0

Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium

Filipe Correia Martins, Dominique Laurent Couturier, Anna Paterson, Anthony N. Karnezis, Christine Chow, Tayyebeh M. Nazeran, Adekunle Odunsi, Aleksandra Gentry-Maharaj, Aleksandra Vrvilo, Alexander Hein, Aline Talhouk, Ana Osorio, Andreas D. Hartkopf, Angela Brooks-Wilson, Anna DeFazio, Anna Fischer, Arndt Hartmann, Brenda Y. Hernandez, Bryan M. McCauley, Chloe KarpinskyjChristiani B. de Sousa, Claus Høgdall, Daniel G. Tiezzi, Esther Herpel, Florin Andrei Taran, Francesmary Modugno, Gary Keeney, Gregg Nelson, Helen Steed, Honglin Song, Hugh Luk, Javier Benitez, Jennifer Alsop, Jennifer M. Koziak, Jenny Lester, Joseph H. Rothstein, Jurandyr M. de Andrade, Lene Lundvall, Luis Paz-Ares, Luis Robles-Díaz, Lynne R. Wilkens, Maria J. Garcia, Maria P. Intermaggio, Marie Lyne Alcaraz, Mary A. Brett, Matthias W. Beckmann, Mercedes Jimenez-Linan, Michael Anglesio, Michael E. Carney, Michael Schneider, Nadia Traficante, Nadja Pejovic, Naveena Singh, Nhu Le, Peter Sinn, Prafull Ghatage, Ramona Erber, Robert Edwards, Robert Vierkant, Roberta B. Ness, Samuel Leung, Sandra Orsulic, Sara Y. Brucker, Scott H. Kaufmann, Sian Fereday, Simon Gayther, Stacey J. Winham, Stefan Kommoss, Tanja Pejovic, Teri A. Longacre, Valerie McGuire, Valerie Rhenius, Weiva Sieh, Yurii B. Shvetsov, Alice S. Whittemore, Annette Staebler, Beth Y. Karlan, Cristina Rodriguez-Antona, David D. Bowtell, Ellen L. Goode, Estrid Høgdall, Francisco J. Candido dos Reis, Jacek Gronwald, Jenny Chang-Claude, Kirsten B. Moysich, Linda E. Kelemen, Linda S. Cook, Marc T. Goodman, Peter A. Fasching, Robin Crawford, Suha Deen, Usha Menon, David G. Huntsman, Martin Köbel, Susan J. Ramus, Paul D.P. Pharoah, James D. Brenton

Obstetrics and Gynecology

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

Background: PTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study. Methods: Tumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran–Mantel–Haenszel tests. Results: Downregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65–0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value < 0.0001). Heterogeneous expression of PTEN was more prevalent in advanced HGSOC (p value = 0.019) and associated with higher CD8 counts (p value = 0.0016). Conclusions: PTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes.

Original language	English (US)
Pages (from-to)	793-802
Number of pages	10
Journal	British Journal of Cancer
Volume	123
Issue number	5
DOIs	https://doi.org/10.1038/s41416-020-0900-0
State	Published - Sep 1 2020

ASJC Scopus subject areas

Oncology
Cancer Research

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Martins, F. C., Couturier, D. L., Paterson, A., Karnezis, A. N., Chow, C., Nazeran, T. M., Odunsi, A., Gentry-Maharaj, A., Vrvilo, A., Hein, A., Talhouk, A., Osorio, A., Hartkopf, A. D., Brooks-Wilson, A., DeFazio, A., Fischer, A., Hartmann, A., Hernandez, B. Y., McCauley, B. M., ... Brenton, J. D. (2020). Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium. British Journal of Cancer, 123(5), 793-802. https://doi.org/10.1038/s41416-020-0900-0

Martins, FC, Couturier, DL, Paterson, A, Karnezis, AN, Chow, C, Nazeran, TM, Odunsi, A, Gentry-Maharaj, A, Vrvilo, A, Hein, A, Talhouk, A, Osorio, A, Hartkopf, AD, Brooks-Wilson, A, DeFazio, A, Fischer, A, Hartmann, A, Hernandez, BY, McCauley, BM, Karpinskyj, C, de Sousa, CB, Høgdall, C, Tiezzi, DG, Herpel, E, Taran, FA, Modugno, F, Keeney, G, Nelson, G, Steed, H, Song, H, Luk, H, Benitez, J, Alsop, J, Koziak, JM, Lester, J, Rothstein, JH, de Andrade, JM, Lundvall, L, Paz-Ares, L, Robles-Díaz, L, Wilkens, LR, Garcia, MJ, Intermaggio, MP, Alcaraz, ML, Brett, MA, Beckmann, MW, Jimenez-Linan, M, Anglesio, M, Carney, ME, Schneider, M, Traficante, N, Pejovic, N, Singh, N, Le, N, Sinn, P, Ghatage, P, Erber, R, Edwards, R, Vierkant, R, Ness, RB, Leung, S, Orsulic, S, Brucker, SY, Kaufmann, SH, Fereday, S, Gayther, S, Winham, SJ, Kommoss, S, Pejovic, T, Longacre, TA, McGuire, V, Rhenius, V, Sieh, W, Shvetsov, YB, Whittemore, AS, Staebler, A, Karlan, BY, Rodriguez-Antona, C, Bowtell, DD, Goode, EL, Høgdall, E, Candido dos Reis, FJ, Gronwald, J, Chang-Claude, J, Moysich, KB, Kelemen, LE, Cook, LS, Goodman, MT, Fasching, PA, Crawford, R, Deen, S, Menon, U, Huntsman, DG, Köbel, M, Ramus, SJ, Pharoah, PDP & Brenton, JD 2020, 'Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium', British Journal of Cancer, vol. 123, no. 5, pp. 793-802. https://doi.org/10.1038/s41416-020-0900-0

@article{2116a846f081403d9680d9220e8d57a0,

title = "Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium",

abstract = "Background: PTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study. Methods: Tumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran–Mantel–Haenszel tests. Results: Downregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65–0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value < 0.0001). Heterogeneous expression of PTEN was more prevalent in advanced HGSOC (p value = 0.019) and associated with higher CD8 counts (p value = 0.0016). Conclusions: PTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes.",

author = "Martins, {Filipe Correia} and Couturier, {Dominique Laurent} and Anna Paterson and Karnezis, {Anthony N.} and Christine Chow and Nazeran, {Tayyebeh M.} and Adekunle Odunsi and Aleksandra Gentry-Maharaj and Aleksandra Vrvilo and Alexander Hein and Aline Talhouk and Ana Osorio and Hartkopf, {Andreas D.} and Angela Brooks-Wilson and Anna DeFazio and Anna Fischer and Arndt Hartmann and Hernandez, {Brenda Y.} and McCauley, {Bryan M.} and Chloe Karpinskyj and {de Sousa}, {Christiani B.} and Claus H{\o}gdall and Tiezzi, {Daniel G.} and Esther Herpel and Taran, {Florin Andrei} and Francesmary Modugno and Gary Keeney and Gregg Nelson and Helen Steed and Honglin Song and Hugh Luk and Javier Benitez and Jennifer Alsop and Koziak, {Jennifer M.} and Jenny Lester and Rothstein, {Joseph H.} and {de Andrade}, {Jurandyr M.} and Lene Lundvall and Luis Paz-Ares and Luis Robles-D{\'i}az and Wilkens, {Lynne R.} and Garcia, {Maria J.} and Intermaggio, {Maria P.} and Alcaraz, {Marie Lyne} and Brett, {Mary A.} and Beckmann, {Matthias W.} and Mercedes Jimenez-Linan and Michael Anglesio and Carney, {Michael E.} and Michael Schneider and Nadia Traficante and Nadja Pejovic and Naveena Singh and Nhu Le and Peter Sinn and Prafull Ghatage and Ramona Erber and Robert Edwards and Robert Vierkant and Ness, {Roberta B.} and Samuel Leung and Sandra Orsulic and Brucker, {Sara Y.} and Kaufmann, {Scott H.} and Sian Fereday and Simon Gayther and Winham, {Stacey J.} and Stefan Kommoss and Tanja Pejovic and Longacre, {Teri A.} and Valerie McGuire and Valerie Rhenius and Weiva Sieh and Shvetsov, {Yurii B.} and Whittemore, {Alice S.} and Annette Staebler and Karlan, {Beth Y.} and Cristina Rodriguez-Antona and Bowtell, {David D.} and Goode, {Ellen L.} and Estrid H{\o}gdall and {Candido dos Reis}, {Francisco J.} and Jacek Gronwald and Jenny Chang-Claude and Moysich, {Kirsten B.} and Kelemen, {Linda E.} and Cook, {Linda S.} and Goodman, {Marc T.} and Fasching, {Peter A.} and Robin Crawford and Suha Deen and Usha Menon and Huntsman, {David G.} and Martin K{\"o}bel and Ramus, {Susan J.} and Pharoah, {Paul D.P.} and Brenton, {James D.}",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = sep,

day = "1",

doi = "10.1038/s41416-020-0900-0",

language = "English (US)",

volume = "123",

pages = "793--802",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

number = "5",

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TY - JOUR

T1 - Clinical and pathological associations of PTEN expression in ovarian cancer

T2 - a multicentre study from the Ovarian Tumour Tissue Analysis Consortium

AU - Martins, Filipe Correia

AU - Couturier, Dominique Laurent

AU - Paterson, Anna

AU - Karnezis, Anthony N.

AU - Chow, Christine

AU - Nazeran, Tayyebeh M.

AU - Odunsi, Adekunle

AU - Gentry-Maharaj, Aleksandra

AU - Vrvilo, Aleksandra

AU - Hein, Alexander

AU - Talhouk, Aline

AU - Osorio, Ana

AU - Hartkopf, Andreas D.

AU - Brooks-Wilson, Angela

AU - DeFazio, Anna

AU - Fischer, Anna

AU - Hartmann, Arndt

AU - Hernandez, Brenda Y.

AU - McCauley, Bryan M.

AU - Karpinskyj, Chloe

AU - de Sousa, Christiani B.

AU - Høgdall, Claus

AU - Tiezzi, Daniel G.

AU - Herpel, Esther

AU - Taran, Florin Andrei

AU - Modugno, Francesmary

AU - Keeney, Gary

AU - Nelson, Gregg

AU - Steed, Helen

AU - Song, Honglin

AU - Luk, Hugh

AU - Benitez, Javier

AU - Alsop, Jennifer

AU - Koziak, Jennifer M.

AU - Lester, Jenny

AU - Rothstein, Joseph H.

AU - de Andrade, Jurandyr M.

AU - Lundvall, Lene

AU - Paz-Ares, Luis

AU - Robles-Díaz, Luis

AU - Wilkens, Lynne R.

AU - Garcia, Maria J.

AU - Intermaggio, Maria P.

AU - Alcaraz, Marie Lyne

AU - Brett, Mary A.

AU - Beckmann, Matthias W.

AU - Jimenez-Linan, Mercedes

AU - Anglesio, Michael

AU - Carney, Michael E.

AU - Schneider, Michael

AU - Traficante, Nadia

AU - Pejovic, Nadja

AU - Singh, Naveena

AU - Le, Nhu

AU - Sinn, Peter

AU - Ghatage, Prafull

AU - Erber, Ramona

AU - Edwards, Robert

AU - Vierkant, Robert

AU - Ness, Roberta B.

AU - Leung, Samuel

AU - Orsulic, Sandra

AU - Brucker, Sara Y.

AU - Kaufmann, Scott H.

AU - Fereday, Sian

AU - Gayther, Simon

AU - Winham, Stacey J.

AU - Kommoss, Stefan

AU - Pejovic, Tanja

AU - Longacre, Teri A.

AU - McGuire, Valerie

AU - Rhenius, Valerie

AU - Sieh, Weiva

AU - Shvetsov, Yurii B.

AU - Whittemore, Alice S.

AU - Staebler, Annette

AU - Karlan, Beth Y.

AU - Rodriguez-Antona, Cristina

AU - Bowtell, David D.

AU - Goode, Ellen L.

AU - Høgdall, Estrid

AU - Candido dos Reis, Francisco J.

AU - Gronwald, Jacek

AU - Chang-Claude, Jenny

AU - Moysich, Kirsten B.

AU - Kelemen, Linda E.

AU - Cook, Linda S.

AU - Goodman, Marc T.

AU - Fasching, Peter A.

AU - Crawford, Robin

AU - Deen, Suha

AU - Menon, Usha

AU - Huntsman, David G.

AU - Köbel, Martin

AU - Ramus, Susan J.

AU - Pharoah, Paul D.P.

AU - Brenton, James D.

PY - 2020/9/1

Y1 - 2020/9/1

N2 - Background: PTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study. Methods: Tumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran–Mantel–Haenszel tests. Results: Downregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65–0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value < 0.0001). Heterogeneous expression of PTEN was more prevalent in advanced HGSOC (p value = 0.019) and associated with higher CD8 counts (p value = 0.0016). Conclusions: PTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes.

AB - Background: PTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study. Methods: Tumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran–Mantel–Haenszel tests. Results: Downregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65–0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value < 0.0001). Heterogeneous expression of PTEN was more prevalent in advanced HGSOC (p value = 0.019) and associated with higher CD8 counts (p value = 0.0016). Conclusions: PTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes.

UR - http://www.scopus.com/inward/record.url?scp=85086506338&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85086506338&partnerID=8YFLogxK

U2 - 10.1038/s41416-020-0900-0

DO - 10.1038/s41416-020-0900-0

M3 - Article

C2 - 32555365

AN - SCOPUS:85086506338

SN - 0007-0920

VL - 123

SP - 793

EP - 802

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 5

ER -

Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium

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