Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study

Weiva Sieh; Martin Köbel; Teri A Longacre; David D Bowtell; Anna deFazio; Marc T Goodman; Estrid Høgdall; Suha Deen; Nicolas Wentzensen; Kirsten B Moysich; James D Brenton; Blaise A Clarke; Usha Menon; C Blake Gilks; Andre Kim; Jason Madore; Sian Fereday; Joshy George; Laura Galletta; Galina Lurie; Lynne R Wilkens; Michael E Carney; Pamela J Thompson; Rayna K Matsuno; Susanne Krüger Kjær; Allan Jensen; Claus Høgdall; Kimberly R Kalli; Brooke L Fridley; Gary L Keeney; Robert A Vierkant; Julie M Cunningham; Louise A Brinton; Hannah P Yang; Mark E Sherman; Montserrat García-Closas; Jolanta Lissowska; Kunle Odunsi; Carl Morrison; Shashikant Lele; Wiam Bshara; Lara Sucheston; Mercedes Jimenez-Linan; Kristy Driver; Jennifer Alsop; Marie Mack; Valerie McGuire; Joseph H Rothstein; Barry P Rosen; Marcus Q Bernardini; Helen Mackay; Amit Oza; Eva L Wozniak; Elizabeth Benjamin; Aleksandra Gentry-Maharaj; Simon A Gayther; Anna V Tinker; Leah M Prentice; Christine Chow; Michael S Anglesio; Sharon E Johnatty; Georgia Chenevix-Trench; Alice S Whittemore; Paul D P Pharoah; Ellen L Goode; David G Huntsman; Susan J Ramus

doi:10.1016/S1470-2045(13)70253-5

Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study

Weiva Sieh, Martin Köbel, Teri A Longacre, David D Bowtell, Anna deFazio, Marc T Goodman, Estrid Høgdall, Suha Deen, Nicolas Wentzensen, Kirsten B Moysich, James D Brenton, Blaise A Clarke, Usha Menon, C Blake Gilks, Andre Kim, Jason Madore, Sian Fereday, Joshy George, Laura Galletta, Galina LurieLynne R Wilkens, Michael E Carney, Pamela J Thompson, Rayna K Matsuno, Susanne Krüger Kjær, Allan Jensen, Claus Høgdall, Kimberly R Kalli, Brooke L Fridley, Gary L Keeney, Robert A Vierkant, Julie M Cunningham, Louise A Brinton, Hannah P Yang, Mark E Sherman, Montserrat García-Closas, Jolanta Lissowska, Kunle Odunsi, Carl Morrison, Shashikant Lele, Wiam Bshara, Lara Sucheston, Mercedes Jimenez-Linan, Kristy Driver, Jennifer Alsop, Marie Mack, Valerie McGuire, Joseph H Rothstein, Barry P Rosen, Marcus Q Bernardini, Helen Mackay, Amit Oza, Eva L Wozniak, Elizabeth Benjamin, Aleksandra Gentry-Maharaj, Simon A Gayther, Anna V Tinker, Leah M Prentice, Christine Chow, Michael S Anglesio, Sharon E Johnatty, Georgia Chenevix-Trench, Alice S Whittemore, Paul D P Pharoah, Ellen L Goode, David G Huntsman, Susan J Ramus

Institut for Klinisk Medicin

216 Citationer (Scopus)

Abstract

Background: Few biomarkers of ovarian cancer prognosis have been established, partly because subtype-specific associations might be obscured in studies combining all histopathological subtypes. We examined whether tumour expression of the progesterone receptor (PR) and oestrogen receptor (ER) was associated with subtype-specific survival. Methods: 12 studies participating in the Ovarian Tumor Tissue Analysis consortium contributed tissue microarray sections and clinical data to our study. Participants included in our analysis had been diagnosed with invasive serous, mucinous, endometrioid, or clear-cell carcinomas of the ovary. For a patient to be eligible, tissue microarrays, clinical follow-up data, age at diagnosis, and tumour grade and stage had to be available. Clinical data were obtained from medical records, cancer registries, death certificates, pathology reports, and review of histological slides. PR and ER statuses were assessed by central immunohistochemistry analysis done by masked pathologists. PR and ER staining was defined as negative (<1% tumour cell nuclei), weak (1 to <50%), or strong (≥50%). Associations with disease-specific survival were assessed. Findings: 2933 women with invasive epithelial ovarian cancer were included: 1742 with high-grade serous carcinoma, 110 with low-grade serous carcinoma, 207 with mucinous carcinoma, 484 with endometrioid carcinoma, and 390 with clear-cell carcinoma. PR expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0·0001) and high-grade serous carcinoma (log-rank p=0·0006), and ER expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0·0001). We recorded no significant associations for mucinous, clear-cell, or low-grade serous carcinoma. Positive hormone-receptor expression (weak or strong staining for PR or ER, or both) was associated with significantly improved disease-specific survival in endometrioid carcinoma compared with negative hormone-receptor expression, independent of study site, age, stage, and grade (hazard ratio 0·33, 95% CI 0·21-0·51; p<0·0001). Strong PR expression was independently associated with improved disease-specific survival in high-grade serous carcinoma (0·71, 0·55-0·91; p=0·0080), but weak PR expression was not (1·02, 0·89-1·18; p=0·74). Interpretation: PR and ER are prognostic biomarkers for endometrioid and high-grade serous ovarian cancers. Clinical trials, stratified by subtype and biomarker status, are needed to establish whether hormone-receptor status predicts response to endocrine treatment, and whether it could guide personalised treatment for ovarian cancer. Funding: Carraresi Foundation and others.

Originalsprog	Engelsk
Tidsskrift	The Lancet Oncology
Vol/bind	14
Udgave nummer	9
Sider (fra-til)	853-862
Antal sider	10
ISSN	1470-2045
DOI	https://doi.org/10.1016/S1470-2045(13)70253-5
Status	Udgivet - aug. 2013

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Sieh, W., Köbel, M., Longacre, T. A., Bowtell, D. D., deFazio, A., Goodman, M. T., Høgdall, E., Deen, S., Wentzensen, N., Moysich, K. B., Brenton, J. D., Clarke, B. A., Menon, U., Gilks, C. B., Kim, A., Madore, J., Fereday, S., George, J., Galletta, L., ... Ramus, S. J. (2013). Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study. The Lancet Oncology, 14(9), 853-862. https://doi.org/10.1016/S1470-2045(13)70253-5

Sieh, W, Köbel, M, Longacre, TA, Bowtell, DD, deFazio, A, Goodman, MT, Høgdall, E, Deen, S, Wentzensen, N, Moysich, KB, Brenton, JD, Clarke, BA, Menon, U, Gilks, CB, Kim, A, Madore, J, Fereday, S, George, J, Galletta, L, Lurie, G, Wilkens, LR, Carney, ME, Thompson, PJ, Matsuno, RK, Kjær, SK, Jensen, A, Høgdall, C, Kalli, KR, Fridley, BL, Keeney, GL, Vierkant, RA, Cunningham, JM, Brinton, LA, Yang, HP, Sherman, ME, García-Closas, M, Lissowska, J, Odunsi, K, Morrison, C, Lele, S, Bshara, W, Sucheston, L, Jimenez-Linan, M, Driver, K, Alsop, J, Mack, M, McGuire, V, Rothstein, JH, Rosen, BP, Bernardini, MQ, Mackay, H, Oza, A, Wozniak, EL, Benjamin, E, Gentry-Maharaj, A, Gayther, SA, Tinker, AV, Prentice, LM, Chow, C, Anglesio, MS, Johnatty, SE, Chenevix-Trench, G, Whittemore, AS, Pharoah, PDP, Goode, EL, Huntsman, DG & Ramus, SJ 2013, 'Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study', The Lancet Oncology, bind 14, nr. 9, s. 853-862. https://doi.org/10.1016/S1470-2045(13)70253-5

@article{06abec4905fd409b8571aeb9e9fd45fc,

title = "Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study",

abstract = "Background: Few biomarkers of ovarian cancer prognosis have been established, partly because subtype-specific associations might be obscured in studies combining all histopathological subtypes. We examined whether tumour expression of the progesterone receptor (PR) and oestrogen receptor (ER) was associated with subtype-specific survival. Methods: 12 studies participating in the Ovarian Tumor Tissue Analysis consortium contributed tissue microarray sections and clinical data to our study. Participants included in our analysis had been diagnosed with invasive serous, mucinous, endometrioid, or clear-cell carcinomas of the ovary. For a patient to be eligible, tissue microarrays, clinical follow-up data, age at diagnosis, and tumour grade and stage had to be available. Clinical data were obtained from medical records, cancer registries, death certificates, pathology reports, and review of histological slides. PR and ER statuses were assessed by central immunohistochemistry analysis done by masked pathologists. PR and ER staining was defined as negative (<1% tumour cell nuclei), weak (1 to <50%), or strong (≥50%). Associations with disease-specific survival were assessed. Findings: 2933 women with invasive epithelial ovarian cancer were included: 1742 with high-grade serous carcinoma, 110 with low-grade serous carcinoma, 207 with mucinous carcinoma, 484 with endometrioid carcinoma, and 390 with clear-cell carcinoma. PR expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0·0001) and high-grade serous carcinoma (log-rank p=0·0006), and ER expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0·0001). We recorded no significant associations for mucinous, clear-cell, or low-grade serous carcinoma. Positive hormone-receptor expression (weak or strong staining for PR or ER, or both) was associated with significantly improved disease-specific survival in endometrioid carcinoma compared with negative hormone-receptor expression, independent of study site, age, stage, and grade (hazard ratio 0·33, 95% CI 0·21-0·51; p<0·0001). Strong PR expression was independently associated with improved disease-specific survival in high-grade serous carcinoma (0·71, 0·55-0·91; p=0·0080), but weak PR expression was not (1·02, 0·89-1·18; p=0·74). Interpretation: PR and ER are prognostic biomarkers for endometrioid and high-grade serous ovarian cancers. Clinical trials, stratified by subtype and biomarker status, are needed to establish whether hormone-receptor status predicts response to endocrine treatment, and whether it could guide personalised treatment for ovarian cancer. Funding: Carraresi Foundation and others.",

author = "Weiva Sieh and Martin K{\"o}bel and Longacre, {Teri A} and Bowtell, {David D} and Anna deFazio and Goodman, {Marc T} and Estrid H{\o}gdall and Suha Deen and Nicolas Wentzensen and Moysich, {Kirsten B} and Brenton, {James D} and Clarke, {Blaise A} and Usha Menon and Gilks, {C Blake} and Andre Kim and Jason Madore and Sian Fereday and Joshy George and Laura Galletta and Galina Lurie and Wilkens, {Lynne R} and Carney, {Michael E} and Thompson, {Pamela J} and Matsuno, {Rayna K} and Kj{\ae}r, {Susanne Kr{\"u}ger} and Allan Jensen and Claus H{\o}gdall and Kalli, {Kimberly R} and Fridley, {Brooke L} and Keeney, {Gary L} and Vierkant, {Robert A} and Cunningham, {Julie M} and Brinton, {Louise A} and Yang, {Hannah P} and Sherman, {Mark E} and Montserrat Garc{\'i}a-Closas and Jolanta Lissowska and Kunle Odunsi and Carl Morrison and Shashikant Lele and Wiam Bshara and Lara Sucheston and Mercedes Jimenez-Linan and Kristy Driver and Jennifer Alsop and Marie Mack and Valerie McGuire and Rothstein, {Joseph H} and Rosen, {Barry P} and Bernardini, {Marcus Q} and Helen Mackay and Amit Oza and Wozniak, {Eva L} and Elizabeth Benjamin and Aleksandra Gentry-Maharaj and Gayther, {Simon A} and Tinker, {Anna V} and Prentice, {Leah M} and Christine Chow and Anglesio, {Michael S} and Johnatty, {Sharon E} and Georgia Chenevix-Trench and Whittemore, {Alice S} and Pharoah, {Paul D P} and Goode, {Ellen L} and Huntsman, {David G} and Ramus, {Susan J}",

year = "2013",

month = aug,

doi = "10.1016/S1470-2045(13)70253-5",

language = "English",

volume = "14",

pages = "853--862",

journal = "The Lancet Oncology",

issn = "1470-2045",

publisher = "TheLancet Publishing Group",

number = "9",

}

TY - JOUR

T1 - Hormone-receptor expression and ovarian cancer survival

T2 - an Ovarian Tumor Tissue Analysis consortium study

AU - Sieh, Weiva

AU - Köbel, Martin

AU - Longacre, Teri A

AU - Bowtell, David D

AU - deFazio, Anna

AU - Goodman, Marc T

AU - Høgdall, Estrid

AU - Deen, Suha

AU - Wentzensen, Nicolas

AU - Moysich, Kirsten B

AU - Brenton, James D

AU - Clarke, Blaise A

AU - Menon, Usha

AU - Gilks, C Blake

AU - Kim, Andre

AU - Madore, Jason

AU - Fereday, Sian

AU - George, Joshy

AU - Galletta, Laura

AU - Lurie, Galina

AU - Wilkens, Lynne R

AU - Carney, Michael E

AU - Thompson, Pamela J

AU - Matsuno, Rayna K

AU - Kjær, Susanne Krüger

AU - Jensen, Allan

AU - Høgdall, Claus

AU - Kalli, Kimberly R

AU - Fridley, Brooke L

AU - Keeney, Gary L

AU - Vierkant, Robert A

AU - Cunningham, Julie M

AU - Brinton, Louise A

AU - Yang, Hannah P

AU - Sherman, Mark E

AU - García-Closas, Montserrat

AU - Lissowska, Jolanta

AU - Odunsi, Kunle

AU - Morrison, Carl

AU - Lele, Shashikant

AU - Bshara, Wiam

AU - Sucheston, Lara

AU - Jimenez-Linan, Mercedes

AU - Driver, Kristy

AU - Alsop, Jennifer

AU - Mack, Marie

AU - McGuire, Valerie

AU - Rothstein, Joseph H

AU - Rosen, Barry P

AU - Bernardini, Marcus Q

AU - Mackay, Helen

AU - Oza, Amit

AU - Wozniak, Eva L

AU - Benjamin, Elizabeth

AU - Gentry-Maharaj, Aleksandra

AU - Gayther, Simon A

AU - Tinker, Anna V

AU - Prentice, Leah M

AU - Chow, Christine

AU - Anglesio, Michael S

AU - Johnatty, Sharon E

AU - Chenevix-Trench, Georgia

AU - Whittemore, Alice S

AU - Pharoah, Paul D P

AU - Goode, Ellen L

AU - Huntsman, David G

AU - Ramus, Susan J

PY - 2013/8

Y1 - 2013/8

N2 - Background: Few biomarkers of ovarian cancer prognosis have been established, partly because subtype-specific associations might be obscured in studies combining all histopathological subtypes. We examined whether tumour expression of the progesterone receptor (PR) and oestrogen receptor (ER) was associated with subtype-specific survival. Methods: 12 studies participating in the Ovarian Tumor Tissue Analysis consortium contributed tissue microarray sections and clinical data to our study. Participants included in our analysis had been diagnosed with invasive serous, mucinous, endometrioid, or clear-cell carcinomas of the ovary. For a patient to be eligible, tissue microarrays, clinical follow-up data, age at diagnosis, and tumour grade and stage had to be available. Clinical data were obtained from medical records, cancer registries, death certificates, pathology reports, and review of histological slides. PR and ER statuses were assessed by central immunohistochemistry analysis done by masked pathologists. PR and ER staining was defined as negative (<1% tumour cell nuclei), weak (1 to <50%), or strong (≥50%). Associations with disease-specific survival were assessed. Findings: 2933 women with invasive epithelial ovarian cancer were included: 1742 with high-grade serous carcinoma, 110 with low-grade serous carcinoma, 207 with mucinous carcinoma, 484 with endometrioid carcinoma, and 390 with clear-cell carcinoma. PR expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0·0001) and high-grade serous carcinoma (log-rank p=0·0006), and ER expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0·0001). We recorded no significant associations for mucinous, clear-cell, or low-grade serous carcinoma. Positive hormone-receptor expression (weak or strong staining for PR or ER, or both) was associated with significantly improved disease-specific survival in endometrioid carcinoma compared with negative hormone-receptor expression, independent of study site, age, stage, and grade (hazard ratio 0·33, 95% CI 0·21-0·51; p<0·0001). Strong PR expression was independently associated with improved disease-specific survival in high-grade serous carcinoma (0·71, 0·55-0·91; p=0·0080), but weak PR expression was not (1·02, 0·89-1·18; p=0·74). Interpretation: PR and ER are prognostic biomarkers for endometrioid and high-grade serous ovarian cancers. Clinical trials, stratified by subtype and biomarker status, are needed to establish whether hormone-receptor status predicts response to endocrine treatment, and whether it could guide personalised treatment for ovarian cancer. Funding: Carraresi Foundation and others.

AB - Background: Few biomarkers of ovarian cancer prognosis have been established, partly because subtype-specific associations might be obscured in studies combining all histopathological subtypes. We examined whether tumour expression of the progesterone receptor (PR) and oestrogen receptor (ER) was associated with subtype-specific survival. Methods: 12 studies participating in the Ovarian Tumor Tissue Analysis consortium contributed tissue microarray sections and clinical data to our study. Participants included in our analysis had been diagnosed with invasive serous, mucinous, endometrioid, or clear-cell carcinomas of the ovary. For a patient to be eligible, tissue microarrays, clinical follow-up data, age at diagnosis, and tumour grade and stage had to be available. Clinical data were obtained from medical records, cancer registries, death certificates, pathology reports, and review of histological slides. PR and ER statuses were assessed by central immunohistochemistry analysis done by masked pathologists. PR and ER staining was defined as negative (<1% tumour cell nuclei), weak (1 to <50%), or strong (≥50%). Associations with disease-specific survival were assessed. Findings: 2933 women with invasive epithelial ovarian cancer were included: 1742 with high-grade serous carcinoma, 110 with low-grade serous carcinoma, 207 with mucinous carcinoma, 484 with endometrioid carcinoma, and 390 with clear-cell carcinoma. PR expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0·0001) and high-grade serous carcinoma (log-rank p=0·0006), and ER expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0·0001). We recorded no significant associations for mucinous, clear-cell, or low-grade serous carcinoma. Positive hormone-receptor expression (weak or strong staining for PR or ER, or both) was associated with significantly improved disease-specific survival in endometrioid carcinoma compared with negative hormone-receptor expression, independent of study site, age, stage, and grade (hazard ratio 0·33, 95% CI 0·21-0·51; p<0·0001). Strong PR expression was independently associated with improved disease-specific survival in high-grade serous carcinoma (0·71, 0·55-0·91; p=0·0080), but weak PR expression was not (1·02, 0·89-1·18; p=0·74). Interpretation: PR and ER are prognostic biomarkers for endometrioid and high-grade serous ovarian cancers. Clinical trials, stratified by subtype and biomarker status, are needed to establish whether hormone-receptor status predicts response to endocrine treatment, and whether it could guide personalised treatment for ovarian cancer. Funding: Carraresi Foundation and others.

U2 - 10.1016/S1470-2045(13)70253-5

DO - 10.1016/S1470-2045(13)70253-5

M3 - Journal article

SN - 1470-2045

VL - 14

SP - 853

EP - 862

JO - The Lancet Oncology

JF - The Lancet Oncology

IS - 9

ER -

Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study

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