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 & 47 others 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 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

Research output: Contribution to journalArticle

158 Citations (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.

Original languageEnglish (US)
Pages (from-to)853-862
Number of pages10
JournalThe Lancet Oncology
Volume14
Issue number9
DOIs
StatePublished - Aug 2013

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Progesterone Receptors
Ovarian Neoplasms
Hormones
Endometrioid Carcinoma
Survival
Carcinoma
Neoplasms
Biomarkers
Staining and Labeling
Mucinous Adenocarcinoma
Death Certificates
Cell Nucleus
Estrogen Receptors
Medical Records
Registries
Ovary
Immunohistochemistry
Clinical Trials
Pathology
Therapeutics

ASJC Scopus subject areas

  • Oncology

Cite this

Sieh, W., Köbel, M., Longacre, T. A., Bowtell, D. D., deFazio, A., Goodman, M. T., ... 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

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

In: The Lancet Oncology, Vol. 14, No. 9, 08.2013, p. 853-862.

Research output: Contribution to journalArticle

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, G, 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, vol. 14, no. 9, pp. 853-862. https://doi.org/10.1016/S1470-2045(13)70253-5
Sieh, Weiva ; Köbel, Martin ; Longacre, Teri A. ; Bowtell, David D. ; deFazio, Anna ; Goodman, Marc T. ; Høgdall, Estrid ; Deen, Suha ; Wentzensen, Nicolas ; Moysich, Kirsten B. ; Brenton, James D. ; Clarke, Blaise A. ; Menon, Usha ; Gilks, C. Blake ; Kim, Andre ; Madore, Jason ; Fereday, Sian ; George, Joshy ; Galletta, Laura ; Lurie, Galina ; Wilkens, Lynne R. ; Carney, Michael E. ; Thompson, Pamela J. ; Matsuno, Rayna K. ; Kjær, Susanne Krüger ; Jensen, Allan ; Høgdall, Claus ; Kalli, Kimberly R. ; Fridley, Brooke L. ; Keeney, Gary ; Vierkant, Robert A. ; Cunningham, Julie M ; Brinton, Louise A. ; Yang, Hannah P. ; Sherman, Mark E. ; García-Closas, Montserrat ; Lissowska, Jolanta ; Odunsi, Kunle ; Morrison, Carl ; Lele, Shashikant ; Bshara, Wiam ; Sucheston, Lara ; Jimenez-Linan, Mercedes ; Driver, Kristy ; Alsop, Jennifer ; Mack, Marie ; McGuire, Valerie ; Rothstein, Joseph H. ; Rosen, Barry P. ; Bernardini, Marcus Q. ; Mackay, Helen ; Oza, Amit ; Wozniak, Eva L. ; Benjamin, Elizabeth ; Gentry-Maharaj, Aleksandra ; Gayther, Simon A. ; Tinker, Anna V. ; Prentice, Leah M. ; Chow, Christine ; Anglesio, Michael S. ; Johnatty, Sharon E. ; Chenevix-Trench, Georgia ; Whittemore, Alice S. ; Pharoah, Paul D P ; Goode, Ellen L ; Huntsman, David G. ; Ramus, Susan J. / Hormone-receptor expression and ovarian cancer survival : An Ovarian Tumor Tissue Analysis consortium study. In: The Lancet Oncology. 2013 ; Vol. 14, No. 9. pp. 853-862.
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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.",
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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

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.

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

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

M3 - Article

VL - 14

SP - 853

EP - 862

JO - The Lancet Oncology

JF - The Lancet Oncology

SN - 1470-2045

IS - 9

ER -