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Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study.
Lancet Oncol. 2013 Aug; 14(9):853-62.LO

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.

Authors+Show Affiliations

Division of Epidemiology, Department of Health Research and Policy, Stanford University, Stanford, CA, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

23845225

Citation

Sieh, Weiva, et al. "Hormone-receptor Expression and Ovarian Cancer Survival: an Ovarian Tumor Tissue Analysis Consortium Study." The Lancet. Oncology, vol. 14, no. 9, 2013, pp. 853-62.
Sieh W, Köbel M, Longacre TA, et al. Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study. Lancet Oncol. 2013;14(9):853-62.
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), 853-62. https://doi.org/10.1016/S1470-2045(13)70253-5
Sieh W, et al. Hormone-receptor Expression and Ovarian Cancer Survival: an Ovarian Tumor Tissue Analysis Consortium Study. Lancet Oncol. 2013;14(9):853-62. PubMed PMID: 23845225.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hormone-receptor expression and ovarian cancer survival: 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, Y1 - 2013/07/09/ PY - 2013/7/13/entrez PY - 2013/7/13/pubmed PY - 2013/10/1/medline SP - 853 EP - 62 JF - The Lancet. Oncology JO - Lancet Oncol VL - 14 IS - 9 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. SN - 1474-5488 UR - https://www.unboundmedicine.com/medline/citation/23845225/Hormone_receptor_expression_and_ovarian_cancer_survival:_an_Ovarian_Tumor_Tissue_Analysis_consortium_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1470-2045(13)70253-5 DB - PRIME DP - Unbound Medicine ER -