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


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.

DOI: 10.1016/S1470-2045(13)70253-5
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@article{Sieh2013HormonereceptorEA, title={Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study.}, author={Weiva Sieh and Martin K{\"{o}bel and Teri A Longacre and David D Bowtell and Anna deFazio and Marc T Goodman and Estrid H\ogdall and Suha Deen and Nicolas Wentzensen and Kirsten B Moysich and James D Brenton and Blaise A Clarke and Usha Menon and C Blake Gilks and Andre Kim and Jason Madore and Sian Fereday and Joshy George and Laura Galletta and Galina Lurie and Lynne R Wilkens and Michael E Carney and Pamela J Thompson and Rayna K Matsuno and Susanne Kr{\"{u}ger Kj{\ae}r and Allan Jensen and Claus H\ogdall and Kimberly R Kalli and Brooke L Fridley and Gary L Keeney and Robert A Vierkant and Julie M Cunningham and Louise A Brinton and Hannah P Yang and Mark E Sherman 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 Joseph H Rothstein and Barry P Rosen and Marcus Q Bernardini and Helen Mackay and Amit Oza and Eva L Wozniak and Elizabeth Benjamin and Aleksandra Gentry-Maharaj and Simon A Gayther and Anna V Tinker and Leah M Prentice and Christine Chow and Michael S Anglesio and Sharon E Johnatty and Georgia Chenevix-Trench and Alice S Whittemore and Paul D P Pharoah and Ellen L Goode and David G Huntsman and Susan J Ramus}, journal={The Lancet. Oncology}, year={2013}, volume={14 9}, pages={853-62} }