Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study - 27/07/13

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

Weiva Sieh, PhD ^a, Martin Köbel, DrMD ^c,^⁎ , Teri A Longacre, ProfMD ^b, David D Bowtell, ProfPhD ^d,^e, Anna deFazio, PhD ^f, Marc T Goodman, PhD ^g, Estrid Høgdall, PhD ^h,ⁱ, Suha Deen, ProfMBChB ^j, Nicolas Wentzensen, MD ^k, Kirsten B Moysich, ProfPhD ^l, James D Brenton, MD ^o,^p,^s, Blaise A Clarke, MD ^t, Usha Menon, ProfMD ^w, C Blake Gilks, ProfMD ^x,^y, Andre Kim, MPH ^z, Jason Madore, MS ^aa, Sian Fereday, BSc ^d, Joshy George, MEng ^d, Laura Galletta, BSc ^d, Galina Lurie, MD ^ac, Lynne R Wilkens, DrPH ^ac, Michael E Carney, MD ^ac, Pamela J Thompson, MPH ^g, Rayna K Matsuno, PhD ^ac, Susanne Krüger Kjær, ProfMD ^h,^ad, Allan Jensen, PhD ^h, Claus Høgdall, ProfMD ^ad, Kimberly R Kalli, PhD ^ae, Brooke L Fridley, PhD ^ak, Gary L Keeney, MD ^af, Robert A Vierkant, MS ^ah,^ai, Julie M Cunningham, PhD ^ag, Louise A Brinton, PhD ^k, Hannah P Yang, PhD ^k, Mark E Sherman, MD ^k, Montserrat García-Closas, ProfDrPH ^al, Jolanta Lissowska, PhD ^am, Kunle Odunsi, ProfMD ^m, Carl Morrison, MD ⁿ, Shashikant Lele, ProfMD ^m, Wiam Bshara, MD ⁿ, Lara Sucheston, PhD ^l, Mercedes Jimenez-Linan, MD ^q,^s, Kristy Driver, BSc ^p, Jennifer Alsop, BA ^p, Marie Mack ^p, Valerie McGuire, PhD ^a, Joseph H Rothstein, MS ^a, Barry P Rosen, ProfMD ^u, Marcus Q Bernardini, MD ^u, Helen Mackay, MD ^v, Amit Oza, ProfMD ^u, Eva L Wozniak, BSc ^w, Elizabeth Benjamin, MD ^an, Aleksandra Gentry-Maharaj, PhD ^w, Simon A Gayther, ProfPhD ^z, Anna V Tinker, MD ^ab, Leah M Prentice, PhD ^aa, Christine Chow, BMLSc ^y, Michael S Anglesio, PhD ^x, Sharon E Johnatty, PhD ^ao, Georgia Chenevix-Trench, ProfPhD ^ao, Alice S Whittemore, ProfPhD ^a, Paul DP Pharoah, ProfPhD ^p,^r, Ellen L Goode, PhD ^aj, David G Huntsman, ProfMD ^x,^aa, Susan J Ramus, PhD ^z

^a Division of Epidemiology, Department of Health Research and Policy, Stanford University, Stanford, CA, USA

^b Department of Pathology, Stanford University, Stanford, CA, USA

^c Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada

^d Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia

^e Department of Biochemistry and Molecular Biology and Sir Peter MacCullum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia

^f Department of Gynaecological Oncology and Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Westmead, NSW, Australia

^g Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA

^h Virus, Lifestyle and Genes Unit, Danish Cancer Society Research Center, Copenhagen, Denmark

ⁱ Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark

^j Department of Histopathology, Queen’s Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK

^k Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA

^l Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA

^m Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA

ⁿ Department of Pathology and Laboratory Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA

^o Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK

^p Department of Oncology, University of Cambridge, Cambridge, UK

^q Department of Pathology, University of Cambridge, Cambridge, UK

^r Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK

^s Addenbrooke’s Hospital, Cambridge University Hospital NHS Foundation Trust and National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, UK

^t Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

^u Department of Obstetrics and Gynecology, University of Toronto, Toronto, ON, Canada

^v Division of Medical Oncology, Department of Medicine, University of Toronto, Toronto, ON, Canada

^w Gynaecological Cancer Research Centre, University College London Elizabeth Garrett Anderson Institute for Women’s Health, London, UK

^x Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada

^y Genetic Pathology Evaluation Centre, Vancouver General Hospital and University of British Columbia, Vancouver, BC, Canada

^z Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA

^aa Centre For Translational and Applied Genomics, British Columbia Cancer Agency, Vancouver, BC, Canada

^ab Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada

^ac Cancer Center, University of Hawaii, Honolulu, HI, USA

^ad The Juliane Marie Center, Department of Obstetrics and Gynecology, Rigshospitalet, Copenhagen, Denmark

^ae Department of Medical Oncology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA

^af Division of Anatomic Pathology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA

^ag Division of Experimental Pathology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA

^ah Department of Laboratory Medicine and Pathology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA

^ai Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA

^aj Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA

^ak Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, USA

^al Institute of Cancer Research, London, UK

^am Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland

^an Department of Pathology, Cancer Institute, University College London, London, UK

^ao Department of Genetics, Queensland Institute of Medical Research, Brisbane, QLD, Australia

^* Correspondence to: Dr Martin Köbel, Department of Pathology and Laboratory Medicine, University of Calgary, 1403 29th Street NW, Calgary, AB T2N 2T9, Canada

Summary

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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Vol 14 - N° 9

P. 853-862 - août 2013 Retour au numéro

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Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study - 27/07/13

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