期刊
LANCET ONCOLOGY
卷 14, 期 9, 页码 853-862出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/S1470-2045(13)70253-5
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资金
- Carraresi Foundation
- University of British Columbia Hospital Foundation
- US Department of Defense [DAMD17-01-1-0729]
- Cancer Council Victoria
- Queensland Cancer Fund
- Cancer Council New South Wales
- Cancer Council South Australia
- Cancer Foundation of Western Australia
- Cancer Council Tasmania
- Australian National Health and Medical Research Council [400413, 400281]
- US National Institutes of Health (NIH) [R01CA58598, N01CN55424, N01PC67001]
- NIH [R01CA61107, R01CA122443, P50CA136393, Z01CP010126, U01CA71966, U01CA69417, R01CA16056, K07CA143047]
- Danish Cancer Society [94 222 52]
- Mermaid I project
- Mayo Foundation
- Fred C and Katherine B Andersen Foundation
- Roswell Park Cancer Institute Alliance Foundation
- Cancer Research UK [C490/A10119, C490/A10124]
- National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre
- Cambridge Experimental Cancer Medicine Centre
- Eve Appeal (Oak Foundation)
- NIHR University College London Hospitals Biomedical Research Centre
- British Columbia Cancer Foundation
- Vancouver General Hospital and University of British Columbia Hospital Foundation
- Sanofi-Aventis Canada
- Cancer Research UK [16561, 15601] Funding Source: researchfish
- Cancer Research UK
- The Francis Crick Institute [10124, 10119] Funding Source: researchfish
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.
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