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Prognostic biomarkers in endometrial and ovarian carcinoma

Abstract

This article reviews the main prognostic and predictive biomarkers of endometrial (EC) and ovarian carcinoma (OC). In EC, prognosis still relies on conventional pathological features such as histological type and grade, as well as myometrial or lymphovascular space invasion. Estrogen receptor, p53, Ki-67, and ploidy analysis are the most promising biomarkers among a long list of molecules that have been proposed. Also, a number of putative predictive biomarkers have been proposed in molecular targeted therapy. In OC, prognosis is predominantly dependent on disease stage at diagnosis and the extent of residual disease at primary operation. Diagnostic markers which aid in establishing histological type in OC are available. However, not a single universally accepted predictive or prognostic marker exists to date. Targeted therapy has been growingly focused at in recent years, in view of the frequent development of chemoresistance at recurrent disease. The present review emphasizes the crucial role of correct pathological classification and stringent selection criteria of the material studied as basis for any evaluation of biological markers. It further emphasizes the promise of targeted therapy in EC and OC, while simultaneously highlighting the difficulties remaining before this can become standard of care.

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References

  1. 1.

    Yeramian A, Moreno-Bueno G, Dolcet X, Catasus L, Abal M, Colas E, Reventos J, Palacios J, Prat J, Matias-Guiu X (2013) Endometrial carcinoma: molecular alterations involved in tumor development and progression. Oncogene 32:403–413

  2. 2.

    Llobet D, Pallares J, Yeramian A, Santacana M, Eritja N, Velasco A, Dolcet X, Matias-Guiu X (2009) Molecular pathology of endometrial carcinoma: practical aspects from the diagnostic and therapeutic viewpoints. J Clin Pathol 62:777–785

  3. 3.

    Lax SF (2004) Molecular genetic pathways in various types of endometrial carcinoma: from a phenotypical to a molecular-based classification. Virchows Arch 444:213–223

  4. 4.

    Hamilton CA, Cheung MK, Osann K, Chen L, Teng NN, Longacre TA, Powell MA, Hendrickson MR, Kapp DS, Chan JK (2006) Uterine papillary serous and clear cell carcinomas predict for poorer survival compared to grade 3 endometrioid corpus cancers. Br J Cancer 4:642–646

  5. 5.

    Salvesen HB, Haldorsen IS, Trovik J (2012) Markers for individualised therapy in endometrial carcinoma. Lancet Oncol 13:353–361

  6. 6.

    Kapucuoglu N, Bulbul D, Tulunay G, Temel MA (2008) Reproducibility of grading systems for endometrial endometrioid carcinoma and their relation with pathologic prognostic parameters. Int J Gynecol Cancer 18:790–796

  7. 7.

    Clarke BA, Gilks CB (2010) Endometrial carcinoma: controversies in histopathological assessment of grade and tumour cell type. J Clin Pathol 63:410–415

  8. 8.

    McConechy MK, Ding J, Cheang MC, Wiegand KC, Senz J, Tone AA, Yang W, Prentice LM, Tse K, Zeng T, McDonald H, Schmidt AP, Mutch DG, McAlpine JN, Hirst M, Shah SP, Lee CH, Goodfellow PJ, Gilks CB, Huntsman DG (2012) Use of mutation profiles to refine the classification of endometrial carcinomas. J Pathol 228:20–30

  9. 9.

    Wright JD, Barrena Medel NI, Sehouli J, Fujiwara K, Herzog TJ (2012) Contemporary management of endometrial cancer. Lancet 379:1352–1360

  10. 10.

    Prat J (2004) Prognostic parameters of endometrial carcinoma. Hum Pathol 35:649–662

  11. 11.

    Gassel AM, Backe J, Krebs S, Schön S, Caffier H, Müller-Hermelink HK (1998) Endometrial carcinoma: immunohistochemically detected proliferation index is a prognosticator of long-term outcome. J Clin Pathol 51:25–29

  12. 12.

    Mhawech-Fauceglia P, Wang D, Samrao D, Liu S, DuPont NC, Pejovic T (2013) Trefoil factor family 3 (TFF3) expression and its interaction with estrogen receptor (ER) in endometrial adenocarcinoma. Gynecol Oncol 130:174–180

  13. 13.

    Jongen V, Briët J, de Jong R, ten Hoor K, Boezen M, van der Zee A, Nijman H, Hollema H (2009) Expression of estrogen receptor-alpha and -beta and progesterone receptor-A and -B in a large cohort of patients with endometrioid endometrial cancer. Gynecol Oncol 112:537–542

  14. 14.

    Trovik J, Wik E, Werner HM, Krakstad C, Helland H, Vandenput I, Njolstad TS, Stefansson IM, Marcickiewicz J, Tingulstad S, Staff AC, Amant F, Akslen LA, Salvesen HB (2013) Hormone receptor loss in endometrial carcinoma curettage predicts lymph node metastasis and poor outcome in prospective multicentre trial. Eur J Cancer. 2013 Aug 8 [Epub ahead of print]

  15. 15.

    Krakstad C, Trovik J, Wik E, Engelsen IB, Werner HM, Birkeland E, Raeder MB, Øyan AM, Stefansson IM, Kalland KH, Akslen LA, Salvesen HB (2012) Loss of GPER identifies new targets for therapy among a subgroup of ERα-positive endometrial cancer patients with poor outcome. Br J Cancer 106:1682–1688

  16. 16.

    Pradhan M, Abeler VM, Danielsen HE, Sandstad B, Tropé CG, Kristensen GB, Risberg B (2012) Prognostic importance of DNA ploidy and DNA index in stage I and II endometrioid adenocarcinoma of the endometrium. Ann Oncol 23:1178–1184

  17. 17.

    Susini T, Amunni G, Molino C, Carriero C, Rapi S, Branconi F, Marchionni M, Taddei G, Scarselli G (2007) Ten-year results of a prospective study on the prognostic role of ploidy in endometrial carcinoma: dNA aneuploidy identifies high-risk cases among the so-called ‘low-risk’ patients with well and moderately differentiated tumors. Cancer 109:882–890

  18. 18.

    Britton LC, Wilson TO, Gaffey TA, Cha SS, Wieand HS, Podratz KC (1990) DNA ploidy in endometrial carcinoma: major objective prognostic factor. Mayo Clin Proc 65:643–650

  19. 19.

    Lindahl B, Ranstam J, Willén R (1994) Five year survival rate in endometrial carcinoma stages I–II: influence of degree of tumour differentiation, age, myometrial invasion and DNA content. Br J Obstet Gynaecol 101:621–625

  20. 20.

    Bonatz G, Lüttges J, Hedderich J, Inform D, Jonat W, Rudolph P, Parwaresch R (1999) Prognostic significance of a novel proliferation marker, anti-repp 86, for endometrial carcinoma: a multivariate study. Hum Pathol 30:949–956

  21. 21.

    Engelsen IB, Stefansson IM, Beroukhim R, Sellers WR, Meyerson M, Akslen LA, Salvesen HB (2008) HER-2/neu expression is associated with high tumor cell proliferation and aggressive phenotype in a population based patient series of endometrial carcinomas. Int J Oncol 32:307–316

  22. 22.

    Bonatz G, Lüttes J, Hamann S, Mettler L, Jonat W, Parwaresch R (1999) Immunohistochemical assessment of p170 provides prognostic information in endometrial carcinoma. Histopathology 34:43–50

  23. 23.

    Ito K, Watanabe K, Nasim S, Sasano H, Sato S, Yajima A, Silverberg SG, Garrett CT (1994) Prognostic significance of p53 overexpression in endometrial cancer. Cancer Res 54:4667–4670

  24. 24.

    Jongen VH, Briët JM, de Jong RA, Joppe E, ten Hoor KA, Boezen HM, Evans DB, Hollema H, van der Zee AG, Nijman HW (2009) Aromatase, cyclooxygenase 2, HER-2/neu, and p53 as prognostic factors in endometrioid endometrial cancer. Int J Gynecol Cancer 19:670–676

  25. 25.

    Hamel NW, Sebo TJ, Wilson TO, Keeney GL, Roche PC, Suman VJ, Hu TC, Podratz KC (1996) Prognostic value of p53 and proliferating cell nuclear antigen expression in endometrial carcinoma. Gynecol Oncol 62:192–198

  26. 26.

    Dupont J, Wang X, Marshall DS, Leitao M, Hedvat CV, Hummer A, Thaler H, O’Reilly RJ, Soslow RA (2004) Wilms Tumor Gene (WT1) and p53 expression in endometrial carcinomas: a study of 130 cases using a tissue microarray. Gynecol Oncol 94:449–455

  27. 27.

    Alkushi A, Lim P, Coldman A, Huntsman D, Miller D, Gilks CB (2004) Interpretation of p53 immunoreactivity in endometrial carcinoma: establishing a clinically relevant cut-off level. Int J Gynecol Pathol 23:129–137

  28. 28.

    Diaz-Padilla I, Romero N, Amir E, Matias-Guiu X, Vilar E, Muggia F, Garcia-Donas J (2013) Mismatch repair status and clinical outcome in endometrial cancer: a systematic review and meta-analysis. Crit Rev Oncol Hematol 2013 Apr 4 [Epub ahead of print]

  29. 29.

    Kanamori Y, Kigawa J, Itamochi H, Sultana H, Suzuki M, Ohwada M, Kamura T, Sugiyama T, Kikuchi Y, Kita T, Fujiwara K, Terakawa N (2002) PTEN expression is associated with prognosis for patients with advanced endometrial carcinoma undergoing postoperative chemotherapy. Int J Cancer 100:686–689

  30. 30.

    Cancer Genome Atlas Research Network, Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, Shen H, Robertson AG, Pashtan I, Shen R, Benz CC, Yau C, Laird PW, Ding L, Zhang W, Mills GB, Kucherlapati R, Mardis ER, Levine DA (2013) Integrated genomic characterization of endometrial carcinoma. Nature 497:67–73

  31. 31.

    Wik E, Birkeland E, Trovik J, Werner HM, Hoivik EA, Mjos S, Krakstad C, Kusonmano K, Mauland K, Stefansson IM, Holst F, Petersen K, Oyan AM, Simon R, Kalland KH, Ricketts W, Akslen LA, Salvesen HB (2013) High phospho-Stathmin(Serine38) expression identifies aggressive endometrial cancer and suggests an association with PI3K inhibition. Clin Cancer Res 19:2331–2341

  32. 32.

    Raeder MB, Birkeland E, Trovik J, Krakstad C, Shehata S, Schumacher S, Zack TI, Krohn A, Werner HM, Moody SE, Wik E, Stefansson IM, Holst F, Oyan AM, Tamayo P, Mesirov JP, Kalland KH, Akslen LA, Simon R, Beroukhim R, Salvesen HB (2013) Integrated genomic analysis of the 8q24 amplification in endometrial cancers identifies ATAD2 as essential to MYC-dependent cancers. PLoS One 8:e54873

  33. 33.

    Byron SA, Gartside M, Powell MA, Wellens CL, Gao F, Mutch DG, Goodfellow PJ, Pollock PM (2012) FGFR2 point mutations in 466 endometrioid endometrial tumors: relationship with MSI, KRAS, PIK3CA, CTNNB1 mutations and clinicopathological features. PLoS One 7:e30801

  34. 34.

    Garcia-Dios DA, Lambrechts D, Coenegrachts L, Vandenput I, Capoen A, Webb PM, Ferguson K, ANECS, Akslen LA, Claes B, Vergote I, Moerman P, Van Robays J, Marcickiewicz J, Salvesen HB, Spurdle AB, Amant F (2013) High-throughput interrogation of PIK3CA, PTEN, KRAS, FBXW7 and TP53 mutations in primary endometrial carcinoma. Gynecol Oncol 128:327–334

  35. 35.

    de Jong RA, Kema IP, Boerma A, Boezen HM, van der Want JJ, Gooden MJ, Hollema H, Nijman HW (2012) Prognostic role of indoleamine 2,3-dioxygenase in endometrial carcinoma. Gynecol Oncol 126:474–480

  36. 36.

    Tempfer C, Haeusler G, Kaider A, Hefler L, Hanzal E, Reinthaller A, Breitenecker G, Kainz C (1998) The prognostic value of CD44 isoform expression in endometrial cancer. Br J Cancer 77:1137–1139

  37. 37.

    Hoshimoto K, Yamauchi N, Takazawa Y, Onda T, Taketani Y, Fukayama M (2003) CD44 variant 6 in endometrioid carcinoma of the uterus: its expression in the adenocarcinoma component is an independent prognostic marker. Pathol Res Pract 199:71–77

  38. 38.

    Engelsen IB, Stefansson I, Akslen LA, Salvesen HB (2006) Pathologic expression of p53 or p16 in preoperative curettage specimens identifies high-risk endometrial carcinomas. Am J Obstet Gynecol 195:979–986

  39. 39.

    Woo MM, Alkushi A, Verhage HG, Magliocco AM, Leung PC, Gilks CB, Auersperg N (2004) Gain of OGP, an estrogen-regulated oviduct-specific glycoprotein, is associated with the development of endometrial hyperplasia and endometrial cancer. Clin Cancer Res 10:7958–7964

  40. 40.

    Li SS, Xue WC, Khoo US, Ngan HY, Chan KY, Tam IY, Chiu PM, Ip PP, Tam KF, Cheung AN (2005) Replicative MCM7 protein as a proliferation marker in endometrial carcinoma: a tissue microarray and clinicopathological analysis. Histopathology 46:307–313

  41. 41.

    Stefansson IM, Salvesen HB, Akslen LA (2004) Prognostic impact of alterations in P-cadherin expression and related cell adhesion markers in endometrial cancer. J Clin Oncol 22:1242–1252

  42. 42.

    Allard JE, Risinger JI, Morrison C, Young G, Rose GS, Fowler J, Berchuck A, Maxwell GL (2007) Overexpression of folate binding protein is associated with shortened progression-free survival in uterine adenocarcinomas. Gynecol Oncol 107:52–57

  43. 43.

    Bachmann IM, Halvorsen OJ, Collett K, Stefansson IM, Straume O, Haukaas SA, Salvesen HB, Otte AP, Akslen LA (2006) EZH2 expression is associated with high proliferation rate and aggressive tumor subgroups in cutaneous melanoma and cancers of the endometrium, prostate, and breast. J Clin Oncol 24:268–273

  44. 44.

    Morrison C, Zanagnolo V, Ramirez N, Cohn DE, Kelbick N, Copeland L, Maxwell GL, Fowler JM (2006) HER-2 is an independent prognostic factor in endometrial cancer: association with outcome in a large cohort of surgically staged patients. J Clin Oncol 24:2376–2385

  45. 45.

    Hetzel DJ, Wilson TO, Keeney GL, Roche PC, Cha SS, Podratz KC (1992) HER-2/neu expression: a major prognostic factor in endometrial cancer. Gynecol Oncol 47:179–185

  46. 46.

    Mhawech-Fauceglia P, Wang D, Syriac S, Godoy H, Dupont N, Liu S, Odunsi K (2012) Synuclein-γ (SNCG) protein expression is associated with poor outcome in endometrial adenocarcinoma. Gynecol Oncol 124:148–152

  47. 47.

    Steinbakk A, Malpica A, Slewa A, Skaland I, Gudlaugsson E, Janssen EA, Løvslett K, Fiane B, Kruse AJ, Feng W, Yinhua Y, Baak JP (2011) Biomarkers and microsatellite instability analysis of curettings can predict the behavior of FIGO stage I endometrial endometrioid adenocarcinoma. Mod Pathol 24:1262–1271

  48. 48.

    Engelsen IB, Stefansson IM, Akslen LA, Salvesen HB (2008) GATA3 expression in estrogen receptor alpha-negative endometrial carcinomas identifies aggressive tumors with high proliferation and poor patient survival. Am J Obstet Gynecol 199(543):e1–e7

  49. 49.

    Tian W, Zhu Y, Wang Y, Teng F, Zhang H, Liu G, Ma X, Sun D, Rohan T, Xue F (2013) Visfatin, a potential biomarker and prognostic factor for endometrial cancer. Gynecol Oncol 129:505–512

  50. 50.

    Salvesen HB, Gulluoglu MG, Stefansson I, Akslen LA (2003) Significance of CD 105 expression for tumour angiogenesis and prognosis in endometrial carcinomas. APMIS 111:1011–1018

  51. 51.

    Birkeland E, Wik E, Mjøs S, Hoivik EA, Trovik J, Werner HM, Kusonmano K, Petersen K, Raeder MB, Holst F, Øyan AM, Kalland KH, Akslen LA, Simon R, Krakstad C, Salvesen HB (2012) KRAS gene amplification and overexpression but not mutation associates with aggressive and metastatic endometrial cancer. Br J Cancer 107:1997–2004

  52. 52.

    Stefansson IM, Salvesen HB, Akslen LA (2006) Loss of p63 and cytokeratin 5/6 expression is associated with more aggressive tumors in endometrial carcinoma patients. Int J Cancer 118:1227–1233

  53. 53.

    Bijen CB, Bantema-Joppe EJ, de Jong RA, Leffers N, Mourits MJ, Eggink HF, van der Zee AG, Hollema H, de Bock GH, Nijman HW (2010) The prognostic role of classical and nonclassical MHC class I expression in endometrial cancer. Int J Cancer 126:1417–1427

  54. 54.

    de Jong RA, Boerma A, Boezen HM, Mourits MJ, Hollema H, Nijman HW (2012) Loss of HLA class I and mismatch repair protein expression in sporadic endometrioid endometrial carcinomas. Int J Cancer 131:1828–1836

  55. 55.

    Mannelqvist M, Stefansson IM, Wik E, Kusonmano K, Raeder MB, Øyan AM, Kalland KH, Moses MA, Salvesen HB, Akslen LA (2012) Lipocalin 2 expression is associated with aggressive features of endometrial cancer. BMC Cancer 12:169

  56. 56.

    Liu Y, Meng F, Xu Y, Yang S, Xiao M, Chen X, Lou G (2013) Overexpression of Wnt7a is associated with tumor progression and unfavorable prognosis in endometrial cancer. Int J Gynecol Cancer 23:304–311

  57. 57.

    Meng F, Li H, Zhou R, Luo C, Hu Y, Lou G (2013) LAPTM4B gene polymorphism and endometrial carcinoma risk and prognosis. Biomarkers 18:136–143

  58. 58.

    Felix AS, Edwards RP, Stone RA, Chivukula M, Parwani AV, Bowser R, Linkov F, Weissfeld JL (2012) Associations between hepatocyte growth factor, c-Met, and basic fibroblast growth factor and survival in endometrial cancer patients. Br J Cancer 106:2004–2009

  59. 59.

    Yao Y, Chen Y, Wang Y, Li X, Wang J, Shen D, Wei L (2010) Molecular classification of human endometrial cancer based on gene expression profiles from specialized microarrays. Int J Gynaecol Obstet 110:125–129

  60. 60.

    Huvila J, Brandt A, Rojas CR, Pasanen S, Talve L, Hirsimäki P, Fey V, Kytömäki L, Saukko P, Carpén O, Soini JT, Grénman S, Auranen A (2009) Gene expression profiling of endometrial adenocarcinomas reveals increased apolipoprotein E expression in poorly differentiated tumors. Int J Gynecol Cancer 19:1226–1231

  61. 61.

    Planagumà J, Díaz-Fuertes M, Gil-Moreno A, Abal M, Monge M, García A, Baró T, Thomson TM, Xercavins J, Alameda F, Reventós J (2004) A differential gene expression profile reveals overexpression of RUNX1/AML1 in invasive endometrioid carcinoma. Cancer Res 64:8846–8853

  62. 62.

    Salvesen HB, Carter SL, Mannelqvist M, Dutt A, Getz G, Stefansson IM, Raeder MB, Sos ML, Engelsen IB, Trovik J, Wik E, Greulich H, Bø TH, Jonassen I, Thomas RK, Zander T, Garraway LA, Oyan AM, Sellers WR, Kalland KH, Meyerson M, Akslen LA, Beroukhim R (2009) Integrated genomic profiling of endometrial carcinoma associates aggressive tumors with indicators of PI3 kinase activation. Proc Natl Acad Sci U S A 106:4834–4839

  63. 63.

    Mannelqvist M, Stefansson IM, Bredholt G, Hellem Bø T, Oyan AM, Jonassen I, Kalland KH, Salvesen HB, Akslen LA (2011) Gene expression patterns related to vascular invasion and aggressive features in endometrial cancer. Am J Pathol 178:861–871

  64. 64.

    Levan K, Partheen K, Osterberg L, Olsson B, Delle U, Eklind S, Horvath G (2010) Identification of a gene expression signature for survival prediction in type I endometrial carcinoma. Gene Expr 14:361–370

  65. 65.

    Ratner ES, Tuck D, Richter C, Nallur S, Patel RM, Schultz V, Hui P, Schwartz PE, Rutherford TJ, Weidhaas JB (2010) MicroRNA signatures differentiate uterine cancer tumor subtypes. Gynecol Oncol 118:251–257

  66. 66.

    Karaayvaz M, Zhang C, Liang S, Shroyer KR, Ju J (2012) Prognostic significance of miR-205 in endometrial cancer. PLoS One 7:e35158

  67. 67.

    Yanokura M, Banno K, Kobayashi Y, Kisu I, Ueki A, Ono A, Masuda K, Nomura H, Hirasawa A, Susumu N, Aoki D (2010) MicroRNA and endometrial cancer: roles of small RNAs in human tumors and clinical applications. Oncol Lett 1:935–940

  68. 68.

    Pijnenborg JM, Romano A, Dam-de Veen GC, Dunselman GA, Fischer DC, Groothuis PG, Kieback DG (2005) Aberrations in the progesterone receptor gene and the risk of recurrent endometrial carcinoma. J Pathol 205:597–605

  69. 69.

    Pijnenborg JM, Dam-de Veen GC, de Haan J, van Engeland M, Groothuis PG (2004) Defective mismatch repair and the development of recurrent endometrial carcinoma. Gynecol Oncol 94:550–559

  70. 70.

    Pijnenborg JM, Kisters N, van Engeland M, Dunselman GA, de Haan J, de Goeij AF, Groothuis PG (2004) APC, beta-catenin, and E-cadherin and the development of recurrent endometrial carcinoma. Int J Gynecol Cancer 14:947–956

  71. 71.

    Santacana M, Yeramian A, Velasco A, Bergada L, García V, Azueta A, Palacios J, Dolcet X, Oliva E, Matias-Guiu X (2012) Immunohistochemical features of post-radiation vaginal recurrences of endometrioid carcinomas of the endometrium. Role for proteins involved in resistance to apoptosis and hypoxia. Histopathology 60:460–471

  72. 72.

    Chaudhry P, Asselin E (2009) Resistance to chemotherapy and hormone therapy in endometrial cancer. Endocr Relat Cancer 16:363–380

  73. 73.

    Hogberg T (2008) Adjuvant chemotherapy in endometrial carcinoma: overview of randomised trials. Clin Oncol (R Coll Radiol) 20:463–469

  74. 74.

    Shoji K, Oda K, Kashiyama T, Ikeda Y, Nakagawa S, Sone K, Miyamoto Y, Hiraike H, Tanikawa M, Miyasaka A, Koso T, Matsumoto Y, Wada-Hiraike O, Kawana K, Kuramoto H, McCormick F, Aburatani H, Yano T, Kozuma S, Taketani Y (2012) Genotype-dependent efficacy of a dual PI3K/mTOR inhibitor, NVP-BEZ235, and an mTOR inhibitor, RAD001, in endometrial carcinomas. PLoS One 7:e37431

  75. 75.

    Dedes KJ, Wetterskog D, Mendes-Pereira AM, Natrajan R, Lambros MB, Geyer FC, Vatcheva R, Savage K, Mackay A, Lord CJ, Ashworth A, Reis-Filho JS (2010) PTEN deficiency in endometrioid endometrial adenocarcinomas predicts sensitivity to PARP inhibitors. Sci Transl Med 2:53ra

  76. 76.

    Diaz-Padilla I, Duran I, Clarke BA, Oza AM (2012) Biologic rationale and clinical activity of mTOR inhibitors in gynecological cancer. Cancer Treat Rev 38:767–775

  77. 77.

    Ortega E, Marti RM, Yeramian A, Sorolla A, Dolcet X, Llobet D, Abal L, Santacana M, Pallares J, Llombart-Cussac A, Matias-Guiu X (2008) Targeted therapies in gynecologic cancers and melanoma. Semin Diagn Pathol 25:262–273

  78. 78.

    Dutt A, Salvesen HB, Chen TH, Ramos AH, Onofrio RC, Hatton C, Nicoletti R, Winckler W, Grewal R, Hanna M, Wyhs N, Ziaugra L, Richter DJ, Trovik J, Engelsen IB, Stefansson IM, Fennell T, Cibulskis K, Zody MC, Akslen LA, Gabriel S, Wong KK, Sellers WR, Meyerson M, Greulich H (2008) Drug-sensitive FGFR2 mutations in endometrial carcinoma. Proc Natl Acad Sci U S A 105:8713–8717

  79. 79.

    Llobet D, Eritja N, Encinas M, Yeramian A, Pallares J, Sorolla A, Santacana M, Gonzalez-Tallada FJ, Matias-Guiu X, Dolcet X (2010) The multikinase inhibitor sorafenib induces apoptosis and sensitizes endometrial cancer cells to TRAIL by different mechanisms. Eur J Cancer 46:836–850

  80. 80.

    Dolcet X, Llobet D, Encinas M, Pallares J, Cabero A, Schoenenberger JA, Comella JX, Matias-Guiu X (2006) Proteasome inhibitors induce death but activate NF-KB on endometrial carcinoma cell lines and primary culture explants. J Biol Chem 281:22118–22130

  81. 81.

    Sorolla A, Yeramian A, Valls J, Dolcet X, Bergadà L, Llombart-Cussac A, Martí RM, Matias-Guiu X (2012) Blockade of NFκB activity by Sunitinib increases cell death in Bortezomib-treated endometrial carcinoma cells. Mol Oncol 6:530–541

  82. 82.

    Bergadà L, Sorolla A, Yeramian A, Eritja N, Mirantes C, Matias-Guiu X, Dolcet X (2013) Combination of Vorinostat and caspase-8 inhibition exhibits high anti-tumoral activity on endometrial cancer cells. Mol Oncol 7:763–775

  83. 83.

    Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62:10–29

  84. 84.

    Hennessy BT, Coleman RL, Markman M (2009) Ovarian cancer. Lancet 374:1371–1382

  85. 85.

    Davidson B, Firat P, Michael CW (eds) (2011) Serous effusions. Springer, London

  86. 86.

    Elstrand MB, Sandstad B, Oksefjell H, Davidson B, Tropé CG (2012) Prognostic significance of residual tumor in patients with epithelial ovarian carcinoma stage IV in a 20 year perspective. Acta Scand Obstet Gynecol 91:308–317

  87. 87.

    Liu G, Yang D, Sun Y, Shmulevich I, Xue F, Sood AK, Zhang W (2012) Differing clinical impact of BRCA1 and BRCA2 mutations in serous ovarian cancer. Pharmacogenomics 13:1523–1535

  88. 88.

    Shih I, Kurman RJ (2004) Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. Am J Pathol 164:1511–1518

  89. 89.

    Köbel M, Kalloger SE, Boyd N, McKinney S, Mehl E, Palmer C, Leung S, Bowen NJ, Ionescu DN, Rajput A, Prentice LM, Miller D, Santos J, Swenerton K, Gilks CB, Huntsman D (2008) Ovarian carcinoma subtypes are different diseases: implications for biomarker studies. PLoS Med 5:e232

  90. 90.

    Prat J (2012) Ovarian carcinomas: five distinct diseases with different origins, genetic alterations, and clinicopathological features. Virchows Arch 460:237–249

  91. 91.

    Kurman RJ, Shih I (2011) Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer-shifting the paradigm. Hum Pathol 42:918–931

  92. 92.

    Kuhn E, Kurman RJ, Vang R, Sehdev AS, Han G, Soslow R, Wang TL, IeM S (2012) TP53 mutations in serous tubal intraepithelial carcinoma and concurrent pelvic high-grade serous carcinoma—evidence supporting the clonal relationship of the two lesions. J Pathol 226:421–426

  93. 93.

    Seidman JD, Zhao P, Yemelyanova A (2011) “Primary peritoneal” high-grade serous carcinoma is very likely metastatic from serous tubal intraepithelial carcinoma: assessing the new paradigm of ovarian and pelvic serous carcinogenesis and its implications for screening for ovarian cancer. Gynecol Oncol 120:470–473

  94. 94.

    Ordóñez NG (2012) Value of PAX 8 immunostaining in tumor diagnosis: a review and update. Adv Anat Pathol 19:140–151

  95. 95.

    Soslow RA (2008) Histologic subtypes of ovarian carcinoma: an overview. Int J Gynecol Pathol 27:161–174

  96. 96.

    Bárcena C, Oliva E (2011) WT1 expression in the female genital tract. Adv Anat Pathol 18:454–465

  97. 97.

    McCluggage WG (2012) Immunohistochemistry in the distinction between primary and metastatic ovarian mucinous neoplasms. J Clin Pathol 65:596–600

  98. 98.

    Leen SL, Singh N (2012) Pathology of primary and metastatic mucinous ovarian neoplasms. J Clin Pathol 65:591–595

  99. 99.

    Delair D, Soslow RA (2012) Key features of extrauterine pelvic serous tumours (fallopian tube, ovary, and peritoneum). Histopathology 61:329–339

  100. 100.

    Gilks CB, Ionescu DN, Kalloger SE, Köbel M, Irving J, Clarke B, Santos J, Le N, Moravan V, Swenerton K, Cheryl Brown Ovarian Cancer Outcomes Unit of the British Columbia Cancer Agency (2008) Tumor cell type can be reproducibly diagnosed and is of independent prognostic significance in patients with maximally debulked ovarian carcinoma. Hum Pathol 39:1239–1251

  101. 101.

    Hwang WT, Adams SF, Tahirovic E, Hagemann IS, Coukos G (2012) Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta-analysis. Gynecol Oncol 124:192–198

  102. 102.

    Lee JY, Myung SK, Song YS (2013) Prognostic role of cyclooxygenase-2 in epithelial ovarian cancer: a meta-analysis of observational studies. Gynecol Oncol 129:613–619

  103. 103.

    Tang Z, Ow GS, Thiery JP, Ivshina AV, Kuznetsov VA (2013) Meta-analysis of transcriptome reveals let-7b as an unfavorable prognostic biomarker and predicts molecular and clinical subclasses in high-grade serous ovarian carcinoma. Int J Cancer 2013 Jul 3 [Epub ahead of print]

  104. 104.

    Wang Y, Wang D, Ren M (2013) Prognostic value of HER-2/neu expression in epithelial ovarian cancer: a meta-analysis. Tumour Biol 2013 Jul 20 [Epub ahead of print]

  105. 105.

    White KL, Vierkant RA, Fogarty ZC, Charbonneau B, Block MS, Pharoah PD, Chenevix-Trench G, or AOCS/ACS group, Rossing MA, Cramer DW, Pearce CL, Schildkraut JM, Menon U, Kjaer SK, Levine DA, Gronwald J, Culver HA, Whittemore AS, Karlan BY, Lambrechts D, Wentzensen N, Kupryjanczyk J, Chang-Claude J, Bandera EV, Hogdall E, Heitz F, Kaye SB, Fasching PA, Campbell I, Goodman MT, Pejovic T, Bean Y, Lurie G, Eccles D, Hein A, Beckmann MW, Ekici AB, Paul J, Brown R, Flanagan JM, Harter P, du Bois A, Schwaab I, Hogdall CK, Lundvall L, Olson SH, Orlow I, Paddock LE, Rudolph A, Eilber U, Dansonka-Mieszkowska A, Rzepecka IK, Ziolkowska-Seta I, Brinton L, Yang H, Garcia-Closas M, Despierre E, Lambrechts S, Vergote I, Walsh C, Lester J, Sieh W, McGuire V, Rothstein JH, Ziogas A, Lubinski J, Cybulski C, Menkiszak J, Jensen A, Gayther SA, Ramus SJ, Gentry-Maharaj A, Berchuck A, Wu AH, Pike MC, Van Denberg D, Terry KL, Vitonis AF, Doherty JA, Johnatty SE, Defazio A, Song H, Tyrer J, Sellers TA, Phelan CM, Kalli KR, Cunningham JM, Fridley BL, Goode EL (2013) Analysis of over 10,000 Cases finds no association between previously reported candidate polymorphisms and ovarian cancer outcome. Cancer Epidemiol Biomarkers Prev 22:987–992

  106. 106.

    Yu L, Deng L, Li J, Zhang Y, Hu L (2013) The prognostic value of vascular endothelial growth factor in ovarian cancer: a systematic review and meta-analysis. Gynecol Oncol 128:391–396

  107. 107.

    Bali A, O’Brien PM, Edwards LS, Sutherland RL, Hacker NF, Henshall SM (2004) Cyclin D1, p53, and p21Waf1/Cip1 expression is predictive of poor clinical outcome in serous epithelial ovarian cancer. Clin Cancer Res 10:5168–5177

  108. 108.

    Ali-Fehmi R, Morris RT, Bandyopadhyay S, Che M, Schimp V, Malone JM Jr, Munkarah AR (2005) Expression of cyclooxygenase-2 in advanced stage ovarian serous carcinoma: correlation with tumor cell proliferation, apoptosis, angiogenesis, and survival. Am J Obstet Gynecol 192:819–825

  109. 109.

    Hsu CY, Bristow R, Cha MS, Wang BG, Ho CL, Kurman RJ, Wang TL, IeM S (2004) Characterization of active mitogen-activated protein kinase in ovarian serous carcinomas. Clin Cancer Res 10:6432–6436

  110. 110.

    Callahan MJ, Nagymanyoki Z, Bonome T, Johnson ME, Litkouhi B, Sullivan EH, Hirsch MS, Matulonis UA, Liu J, Birrer MJ, Berkowitz RS, Mok SC (2008) Increased HLA-DMB expression in the tumor epithelium is associated with increased CTL infiltration and improved prognosis in advanced-stage serous ovarian cancer. Clin Cancer Res 14:7667–7673

  111. 111.

    O’Brien PM, Davies MJ, Scurry JP, Smith AN, Barton CA, Henderson MJ, Saunders DN, Gloss BS, Patterson KI, Clancy JL, Heinzelmann-Schwarz VA, Murali R, Scolyer RA, Zeng Y, Williams ED, Scurr L, Defazio A, Quinn DI, Watts CK, Hacker NF, Henshall SM, Sutherland RL (2008) The E3 ubiquitin ligase EDD is an adverse prognostic factor for serous epithelial ovarian cancer and modulates cisplatin resistance in vitro. Br J Cancer 98:1085–1093

  112. 112.

    Ahmed AA, Etemadmoghadam D, Temple J, Lynch AG, Riad M, Sharma R, Stewart C, Fereday S, Caldas C, Defazio A, Bowtell D, Brenton JD (2010) Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary. J Pathol 221:49–56

  113. 113.

    Li C, Li Y, Wang X, Wang Z, Cai J, Wang L, Zhao Y, Song H, Meng X, Ning X, Xu C, Lin M, Li L, Geng J (2012) Elevated expression of astrocyte elevated gene-1 (AEG-1) is correlated with cisplatin-based chemoresistance and shortened outcome in patients with stages III-IV serous ovarian carcinoma. Histopathology 60:953–963

  114. 114.

    Mhawech-Fauceglia P, Wang D, Samrao D, Godoy H, Ough F, Liu S, Pejovic T, Lele S (2012) Pair Box 8 (PAX8) protein expression in high grade, late stage (stages III and IV) ovarian serous carcinoma. Gynecol Oncol 127:198–201

  115. 115.

    Darb-Esfahani S, Fritzsche F, Kristiansen G, Weichert W, Sehouli J, Braicu I, Dietel M, Denkert C (2012) Anterior gradient protein 2 (AGR2) is an independent prognostic factor in ovarian high-grade serous carcinoma. Virchows Arch 461:109–116

  116. 116.

    Gan A, Green AR, Nolan CC, Martin S, Deen S (2013) Poly(adenosine diphosphate-ribose) polymerase expression in BRCA-proficient ovarian high-grade serous carcinoma; association with patient survival. Hum Pathol 44:1638–1647

  117. 117.

    Huang J, Zhang J, Li H, Lu Z, Shan W, Mercado-Uribe I, Liu J (2013) VCAM1 expression correlated with tumorigenesis and poor prognosis in high grade serous ovarian cancer. Am J Transl Res 5:336–346

  118. 118.

    Tsofack SP, Meunier L, Sanchez L, Madore J, Provencher D, Mes-Masson AM, Lebel M (2013) Low expression of the X-linked ribosomal protein S4 in human serous epithelial ovarian cancer is associated with a poor prognosis. BMC Cancer 13:303

  119. 119.

    Zaid TM, Yeung TL, Thompson MS, Leung CS, Harding T, Co NN, Schmandt RS, Kwan SY, Rodriguez-Aguay C, Lopez-Berestein G, Sood AK, Wong KK, Birrer MJ, Mok SC (2013) Identification of FGFR4 as a potential therapeutic target for advanced-stage, high-grade serous ovarian cancer. Clin Cancer Res 19:809–820

  120. 120.

    Liebscher CA, Prinzler J, Sinn BV, Budczies J, Denkert C, Noske A, Sehouli J, Braicu EI, Dietel M, Darb-Esfahani S (2013) Aldehyde dehydrogenase 1/epidermal growth factor receptor coexpression is characteristic of a highly aggressive, poor-prognosis subgroup of high-grade serous ovarian carcinoma. Hum Pathol 44:1465–1471

  121. 121.

    Brown LA, Kalloger SE, Miller MA, IeM S, McKinney SE, Santos JL, Swenerton K, Spellman PT, Gray J, Gilks CB, Huntsman DG (2008) Amplification of 11q13 in ovarian carcinoma. Genes Chromosome Cancer 47:481–489

  122. 122.

    Yang F, Guo X, Yang G, Rosen DG, Liu J (2011) AURKA and BRCA2 expression highly correlate with prognosis of endometrioid ovarian carcinoma. Mod Pathol 24:836–845

  123. 123.

    Tanabe H, Nishii H, Sakata A, Suzuki K, Mori Y, Shinozaki H, Watanabe A, Ochiai K, Yasuda M, Tanaka T (2004) Overexpression of HER-2/neu is not a risk factor in ovarian clear cell adenocarcinoma. Gynecol Oncol 94:735–739

  124. 124.

    Yamamoto S, Tsuda H, Miyai K, Takano M, Tamai S, Matsubara O (2011) Gene amplification and protein overexpression of MET are common events in ovarian clear-cell adenocarcinoma: their roles in tumor progression and prognostication of the patient. Mod Pathol 24:1146–1155

  125. 125.

    Yamamoto S, Tsuda H, Takano M, Tamai S, Matsubara O (2012) PIK3CA mutations and loss of ARID1A protein expression are early events in the development of cystic ovarian clear cell adenocarcinoma. Virchows Arch 460:77–87

  126. 126.

    Rahman MT, Nakayama K, Rahman M, Nakayama N, Ishikawa M, Katagiri A, Iida K, Nakayama S, Otsuki Y, IeM S, Miyazaki K (2012) Prognostic and therapeutic impact of the chromosome 20q13.2 ZNF217 locus amplification in ovarian clear cell carcinoma. Cancer 118:2846–2857

  127. 127.

    Katagiri A, Nakayama K, Rahman MT, Rahman M, Katagiri H, Nakayama N, Ishikawa M, Ishibashi T, Iida K, Kobayashi H, Otsuki Y, Nakayama S, Miyazaki K (2012) Loss of ARID1A expression is related to shorter progression-free survival and chemoresistance in ovarian clear cell carcinoma. Mod Pathol 25:282–288

  128. 128.

    Abe A, Minaguchi T, Ochi H, Onuki M, Okada S, Matsumoto K, Satoh T, Oki A, Yoshikawa H (2013) PIK3CA overexpression is a possible prognostic factor for favorable survival in ovarian clear cell carcinoma. Hum Pathol 44:199–207

  129. 129.

    Min KW, Park MH, Hong SR, Lee H, Kwon SY, Hong SH, Joo HJ, Park IA, An HJ, Suh KS, Oh HK, Yoo CW, Kim MJ, Chang HK, Jun SY, Yoon HK, Chang ED, Kim DW, Kim I, Gynecologic Pathology Study Group of the Korean Society of Pathologists (2013) Clear cell carcinomas of the ovary: a multi-institutional study of 129 cases in Korea with prognostic significance of Emi1 and Galectin-3. Int J Gynecol Pathol 32:3–14

  130. 130.

    Weichert W, Denkert C, Noske A, Darb-Esfahani S, Dietel M, Kalloger SE, Huntsman DG, Köbel M (2008) Expression of class I histone deacetylases indicates poor prognosis in endometrioid subtypes of ovarian and endometrial carcinomas. Neoplasia 10:1021–1027

  131. 131.

    Prentice LM, Klausen C, Kalloger S, Köbel M, McKinney S, Santos JL, Kenney C, Mehl E, Gilks CB, Leung P, Swenerton K, Huntsman DG, Aparicio SA (2007) Kisspeptin and GPR54 immunoreactivity in a cohort of 518 patients defines favourable prognosis and clear cell subtype in ovarian carcinoma. BMC Med 5:33

  132. 132.

    Köbel M, Xu H, Bourne PA, Spaulding BO, IeM S, Mao TL, Soslow RA, Ewanowich CA, Kalloger SE, Mehl E, Lee CH, Huntsman D, Gilks CB (2009) IGF2BP3 (IMP3) expression is a marker of unfavorable prognosis in ovarian carcinoma of clear cell subtype. Mod Pathol 22:469–475

  133. 133.

    Spowart JE, Townsend KN, Huwait H, Eshragh S, West NR, Ries JN, Kalloger S, Anglesio M, Gorski SM, Watson PH, Gilks CB, Huntsman DG, Lum JJ (2012) The autophagy protein LC3A correlates with hypoxia and is a prognostic marker of patient survival in clear cell ovarian cancer. J Pathol 228:437–447

  134. 134.

    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 GL, 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 PD, Goode EL, Huntsman DG, Ramus SJ (2013) Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study. Lancet Oncol 14:853–862

  135. 135.

    Clarke B, Tinker AV, Lee CH, Subramanian S, van de Rijn M, Turbin D, Kalloger S, Han G, Ceballos K, Cadungog MG, Huntsman DG, Coukos G, Gilks CB (2009) Intraepithelial T cells and prognosis in ovarian carcinoma: novel associations with stage, tumor type, and BRCA1 loss. Mod Pathol 22:393–402

  136. 136.

    Pinke DE, Kalloger SE, Francetic T, Huntsman DG, Lee JM (2008) The prognostic significance of elongation factor eEF1A2 in ovarian cancer. Gynecol Oncol 108:561–568

  137. 137.

    Milne K, Köbel M, Kalloger SE, Barnes RO, Gao D, Gilks CB, Watson PH, Nelson BH (2009) Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors. PLoS One 4:e6412

  138. 138.

    Kildal W, Risberg B, Abeler VM, Kristensen GB, Sudbø J, Nesland JM, Danielsen HE (2005) beta-catenin expression, DNA ploidy and clinicopathological features in ovarian cancer: a study in 253 patients. Eur J Cancer 41:1127–1134

  139. 139.

    Yamamoto S, Tsuda H, Honda K, Kita T, Takano M, Tamai S, Inazawa J, Yamada T, Matsubara O (2007) Actinin-4 expression in ovarian cancer: a novel prognostic indicator independent of clinical stage and histological type. Mod Pathol 20:1278–1285

  140. 140.

    de Graeff P, Crijns AP, Ten Hoor KA, Klip HG, Hollema H, Oien K, Bartlett JM, Wisman GB, de Bock GH, de Vries EG, de Jong S, van der Zee AG (2008) The ErbB signalling pathway: protein expression and prognostic value in epithelial ovarian cancer. Br J Cancer 99:341–349

  141. 141.

    Leffers N, Gooden MJ, Mokhova AA, Kast WM, Boezen HM, Ten Hoor KA, Hollema H, Daemen T, van der Zee AG, Nijman HW (2009) Down-regulation of proteasomal subunit MB1 is an independent predictor of improved survival in ovarian cancer. Gynecol Oncol 113:256–263

  142. 142.

    Leffers N, Gooden MJ, de Jong RA, Hoogeboom BN, ten Hoor KA, Hollema H, Boezen HM, van der Zee AG, Daemen T, Nijman HW (2009) Prognostic significance of tumor-infiltrating T-lymphocytes in primary and metastatic lesions of advanced stage ovarian cancer. Cancer Immunol Immunother 58:449–459

  143. 143.

    Weberpals JI, Tu D, Squire JA, Amin MS, Islam S, Pelletier LB, O'Brien AM, Hoskins PJ, Eisenhauer EA (2011) Breast cancer 1 (BRCA1) protein expression as a prognostic marker in sporadic epithelial ovarian carcinoma: an NCIC CTG OV.16 correlative study. Ann Oncol 22:2403–2410

  144. 144.

    Carser JE, Quinn JE, Michie CO, O’Brien EJ, McCluggage WG, Maxwell P, Lamers E, Lioe TF, Williams AR, Kennedy RD, Gourley C, Harkin DP (2011) BRCA1 is both a prognostic and predictive biomarker of response to chemotherapy in sporadic epithelial ovarian cancer. Gynecol Oncol 123:492–498

  145. 145.

    Aust S, Bachmayr-Heyda A, Pateisky P, Tong D, Darb-Esfahani S, Denkert C, Chekerov R, Sehouli J, Mahner S, Van Gorp T, Vergote I, Speiser P, Horvat R, Zeillinger R, Pils D (2012) Role of TRAP1 and estrogen receptor alpha in patients with ovarian cancer—a study of the OVCAD consortium. Mol Cancer 11:69

  146. 146.

    Rubatt JM, Darcy KM, Tian C, Muggia F, Dhir R, Armstrong DK, Bookman MA, Niedernhofer LJ, Deloia J, Birrer M, Krivak TC (2012) Pre-treatment tumor expression of ERCC1 in women with advanced stage epithelial ovarian cancer is not predictive of clinical outcomes: a Gynecologic Oncology Group study. Gynecol Oncol 125:421–426

  147. 147.

    Marmé F, Hielscher T, Hug S, Bondong S, Zeillinger R, Castillo-Tong DC, Sehouli J, Braicu I, Vergote I, Isabella C, Mahner S, Ferschke I, Rom J, Sohn C, Schneeweiss A, Altevogt P (2012) Fibroblast growth factor receptor 4 gene (FGFR4) 388Arg allele predicts prolonged survival and platinum sensitivity in advanced ovarian cancer. Int J Cancer 131:E586–E591

  148. 148.

    Palmieri C, Gojis O, Rudraraju B, Stamp-Vincent C, Wilson D, Langdon S, Gourley C, Faratian D (2013) Expression of steroid receptor coactivator 3 in ovarian epithelial cancer is a poor prognostic factor and a marker for platinum resistance. Br J Cancer 108:2039–2044

  149. 149.

    Bondong S, Kiefel H, Hielscher T, Zeimet AG, Zeillinger R, Pils D, Schuster E, Castillo-Tong DC, Cadron I, Vergote I, Braicu I, Sehouli J, Mahner S, Fogel M, Altevogt P (2012) Prognostic significance of L1CAM in ovarian cancer and its role in constitutive NF-κB activation. Ann Oncol 23:1795–1802

  150. 150.

    Kleinberg L, Dong HP, Holth A, Risberg B, Trope' CG, Nesland JM, Flørenes VA, Davidson B (2009) Cleaved caspases and NF-κB p65 are prognostic factors in metastatic ovarian carcinoma. Hum Pathol 40:795–806

  151. 151.

    Stavnes HT, Holth A, Don T, Kærn J, Vaksman O, Reich R, Trope' CG, Davidson B (2013) HOXB8 expression in ovarian serous carcinoma effusions is associated with shorter survival. Gynecol Oncol 129:358–363

  152. 152.

    Hetland TE, Hellesylt E, Flørenes VA, Tropé CG, Davidson B, Kærn J (2011) Class III beta-tubulin expression in advanced-stage serous ovarian carcinoma effusions is associated with poor survival and primary chemoresistance. Hum Pathol 42:1019–1026

  153. 153.

    Bock AJ, Tuft Stavnes H, Kærn J, Berner A, Staff AC, Davidson B (2011) Endoglin (CD105) expression in ovarian serous carcinoma effusions is related to chemotherapy status. Tumor Biol 32:589–596

  154. 154.

    Brusegard K, Stavnes HT, Nymoen DA, Flatmark K, Trope' CG, Davidson B (2012) Rab25 is overexpressed in Müllerian serous carcinoma compared to malignant mesothelioma. Virchows Arch 460:193–202

  155. 155.

    Elstrand MB, Stavnes HT, Tropé CG, Davidson B (2012) Heat shock protein 90 is a putative therapeutic target in patients with recurrent advanced-stage ovarian carcinoma with serous effusions. Hum Pathol 43:529–535

  156. 156.

    Davidson B, Holth A, Nguyen MT, Tropé CG, Wu C (2013) Migfilin, α-parvin and β-parvin are differentially expressed in ovarian serous carcinoma effusions, primary tumors and solid metastases. Gynecol Oncol 128:364–370

  157. 157.

    Tothill RW, Tinker AV, George J, Brown R, Fox SB, Lade S, Johnson DS, Trivett MK, Etemadmoghadam D, Locandro B, Traficante N, Fereday S, Hung JA, Chiew YE, Haviv I, Australian Ovarian Cancer Study Group (2008) Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome. Clin Cancer Res 14:5198–5208

  158. 158.

    Sfakianos GP, Iversen ES, Whitaker R, Akushevich L, Schildkraut JM, Murphy SK, Marks JR, Berchuck A (2013) Validation of ovarian cancer gene expression signatures for survival and subtype in formalin fixed paraffin embedded tissues. Gynecol Oncol 129:159–164

  159. 159.

    Cancer Genome Atlas Research Network (2011) Integrated genomic analyses of ovarian carcinoma. Nature 474:609–615

  160. 160.

    Kang J, D’Andrea AD, Kozono D (2012) A DNA repair pathway-focused score for prediction of outcomes in ovarian cancer treated with platinum-based chemotherapy. J Natl Cancer Inst 104:670–681

  161. 161.

    Sohn I, Jung WY, Sung CO (2012) Somatic hypermutation and outcomes of platinum based chemotherapy in patients with high grade serous ovarian cancer. Gynecol Oncol 126:103–108

  162. 162.

    Verhaak RG, Tamayo P, Yang JY, Hubbard D, Zhang H, Creighton CJ, Fereday S, Lawrence M, Carter SL, Mermel CH, Kostic AD, Etemadmoghadam D, Saksena G, Cibulskis K, Duraisamy S, Levanon K, Sougnez C, Tsherniak A, Gomez S, Onofrio R, Gabriel S, Chin L, Zhang N, Spellman PT, Zhang Y, Akbani R, Hoadley KA, Kahn A, Köbel M, Huntsman D, Soslow RA, Defazio A, Birrer MJ, Gray JW, Weinstein JN, Bowtell DD, Drapkin R, Mesirov JP, Getz G, Levine DA, Meyerson M, Cancer Genome Atlas Research Network (2013) Prognostically relevant gene signatures of high-grade serous ovarian carcinoma. J Clin Invest 123:517–525

  163. 163.

    Konstantinopoulos PA, Cannistra SA, Fountzilas H, Culhane A, Pillay K, Rueda B, Cramer D, Seiden M, Birrer M, Coukos G, Zhang L, Quackenbush J, Spentzos D (2011) Integrated analysis of multiple microarray datasets identifies a reproducible survival predictor in ovarian cancer. PLoS One 6:e18202

  164. 164.

    Sabatier R, Finetti P, Bonensea J, Jacquemier J, Adelaide J, Lambaudie E, Viens P, Birnbaum D, Bertucci F (2011) A seven-gene prognostic model for platinum-treated ovarian carcinomas. Br J Cancer 105:304–311

  165. 165.

    Trinh XB, Tjalma WA, Dirix LY, Vermeulen PB, Peeters DJ, Bachvarov D, Plante M, Berns EM, Helleman J, Van Laere SJ, van Dam PA (2011) Microarray-based oncogenic pathway profiling in advanced serous papillary ovarian carcinoma. PLoS One 6:e22469

  166. 166.

    Schwede M, Spentzos D, Bentink S, Hofmann O, Haibe-Kains B, Harrington D, Quackenbush J, Culhane AC (2013) Stem cell-like gene expression in ovarian cancer predicts type II subtype and prognosis. PLoS One 8:e57799

  167. 167.

    Tan DS, Iravani M, McCluggage WG, Lambros MB, Milanezi F, Mackay A, Gourley C, Geyer FC, Vatcheva R, Millar J, Thomas K, Natrajan R, Savage K, Fenwick K, Williams A, Jameson C, El-Bahrawy M, Gore ME, Gabra H, Kaye SB, Ashworth A, Reis-Filho JS (2011) Genomic analysis reveals the molecular heterogeneity of ovarian clear cell carcinomas. Clin Cancer Res 17:1521–1534

  168. 168.

    Tan TZ, Miow QH, Huang RY, Wong MK, Ye J, Lau JA, Wu MC, Bin Abdul Hadi LH, Soong R, Choolani M, Davidson B, Nesland JM, Wang LZ, Matsumura N, Mandai M, Konishi I, Goh BC, Chang JT, Thiery JP, Mori S (2013) Functional genomics identifies five distinct molecular subtypes with clinical relevance and pathways for growth control in epithelial ovarian cancer. Embo Mol Med 5:983–998

  169. 169.

    Banerjee S, Kaye SB (2013) New strategies in the treatment of ovarian cancer: current clinical perspectives and future potential. Clin Cancer Res 19:961–968

  170. 170.

    Morotti M, Becker CM, Menada MV, Ferrero S (2013) Targeting tyrosine-kinases in ovarian cancer. Expert Opin Investig Drugs 2013 Jul 2 [Epub ahead of print]

  171. 171.

    Walters CL, Arend RC, Armstrong DK, Naumann RW, Alvarez RD (2013) Folate and folate receptor alpha antagonists mechanism of action in ovarian cancer. Gynecol Oncol 2013 Jul 14 [Epub ahead of print]

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Acknowledgments

Supported by grants 2009SGR794, FIS RD12/0036/0013, Fundación Asociación Española contra el Cancer, and programa de intensificación de la investigación to XMG and by the Inger and John Fredriksen Foundation for Ovarian Cancer Research to BD

Conflict of interest

The authors declare no conflict of interest

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Correspondence to Xavier Matias-Guiu or Ben Davidson.

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Author contributions

XM and BD were responsible for the study design. XM performed the search and analysis of prognostic and predictive factors in endometrial carcinoma. BD performed the search and analysis of prognostic and predictive factors in ovarian carcinoma. XM and BD were involved in drafting and approving the final version of the manuscript.

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Matias-Guiu, X., Davidson, B. Prognostic biomarkers in endometrial and ovarian carcinoma. Virchows Arch 464, 315–331 (2014). https://doi.org/10.1007/s00428-013-1509-y

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Keywords

  • Endometrial carcinoma
  • Ovarian carcinoma
  • Biomarkers
  • Prognosis