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Uterine carcinosarcoma: Contemporary clinical summary, molecular updates, and future research opportunity

  • Author Footnotes
    1 Contributed equally to the work.
    Shinya Matsuzaki
    Footnotes
    1 Contributed equally to the work.
    Affiliations
    Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA

    Department of Obstetrics and Gynecology, Osaka University, Osaka, Japan
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  • Maximilian Klar
    Affiliations
    Department of Obstetrics and Gynecology, University of Freiburg, Freiburg, Germany
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  • Satoko Matsuzaki
    Affiliations
    Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA

    Department of Obstetrics and Gynecology, Osaka University, Osaka, Japan
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  • Lynda D. Roman
    Affiliations
    Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA

    Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA
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  • Anil K. Sood
    Affiliations
    Department of Gynecologic Oncology and Reproductive Medicine, University of Texas, MD-Anderson Cancer Center, Houston, TX, USA
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  • Author Footnotes
    1 Contributed equally to the work.
    Koji Matsuo
    Correspondence
    Corresponding author at: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, 2020 Zonal Avenue, IRD 520, Los Angeles, CA 90033, USA.
    Footnotes
    1 Contributed equally to the work.
    Affiliations
    Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA

    Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA
    Search for articles by this author
  • Author Footnotes
    1 Contributed equally to the work.
Published:November 09, 2020DOI:https://doi.org/10.1016/j.ygyno.2020.10.043

      Highlights

      • The incidence of uterine carcinosarcoma (UCS) has gradually increased in the United States in recent years.
      • Salient demographic changes in UCS include younger age at diagnosis, stage shift, and multimodality treatment.
      • Survival outcome of UCS remains dismal, and 5-year overall survival rate has not improved in the past several decades (<40%).
      • UCS tumors are serous-like; common somatic mutations include those in TP53, PIK3CA, FBXW7, PTEN, PPP2R1A, and ARID1A genes.
      • Epithelial-to-mesenchymal transition plays a pivotal role in UCS pathogenesis (higher signature and heterologous sarcoma).

      Abstract

      Uterine carcinosarcoma (UCS) is a biphasic aggressive high-grade endometrial cancer in which the sarcoma element has de-differentiated from the carcinoma element. UCS is considered a rare tumor, but its incidence has gradually increased in recent years (annual percent change from 2000 to 2016 1.7%, 95% confidence interval 1.2–2.2) as has the proportion of UCS among endometrial cancer, exceeding 5% in recent years. UCS typically affects the elderly, but in recent decades patients became younger. Notably, a stage-shift has occurred in recent years with increasing nodal metastasis and decreasing distant metastasis. The concept of sarcoma dominance may be new in UCS, and a sarcomatous element >50% of the uterine tumor is associated with decreased survival. Multimodal treatment is the mainstay of UCS. Lymphadenectomy, chemotherapy, and brachytherapy have increased in the past few decades, but survival outcomes remain dismal: the median survival is less than two years, and the 5-year overall survival rate has not changed in decades (31.9% in 1975 to 33.8% in 2012). Carboplatin/paclitaxel adjuvant chemotherapy improves progression-free survival compared with ifosfamide/paclitaxel, particularly in stages III-IV disease (GOG-261 trial). Twenty-six clinical trials previously examined therapeutic effectiveness in recurrent/metastatic UCS. The median response rate and progression-free survival were 37.5% and 5.9 months, respectively, after first-line therapy, but after later therapies, the outcomes were far worse (5.5% and 1.8 months, respectively). One significant discovery was that epithelial-mesenchymal transition (EMT) plays a pivotal role in the pathogenesis of sarcomatous dedifferentiation in UCS and that heterologous sarcoma is associated with a higher EMT signature compared with homologous sarcoma. Furthermore, next-generation sequencing has revealed that UCS tumors are serous-like and that common somatic mutations include those in TP53, PIK3CA, FBXW7, PTEN, and ARID1A. This contemporary review highlights recent clinical and molecular updates in UCS. A possible therapeutic target of EMT in UCS is also discussed.

      Keywords

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