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  1. Shazia Bashir, MD*,
  2. Gaofeng Jiang, PhD,
  3. Ayesha Joshi, PhD,
  4. Christopher Miller, MS,
  5. Cathleen Matrai, MD,
  6. Anna Yemelyanova, MD,
  7. Thomas A. Caputo, MD*,
  8. Kevin M. Holcomb, MD*,
  9. Lora Hedrick Ellenson, MD and
  10. Divya Gupta, MD*
  1. *Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, and
  2. Division of Gynecologic Pathology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York–Presbyterian Hospital, New York, NY; and
  3. Division of Gynecologic Pathology, Department of Pathology, Johns Hopkins Hospital, Baltimore, MD.
  1. Address correspondence and reprint requests to Divya Gupta, MD, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Weill Medical College of Cornell University, 525 E, 68th St, Suite J130, New York, NY 10065. E-mail: dig2010{at}med.cornell.edu.

Abstract

Objectives Type II endometrial carcinomas—uterine carcinosarcomas or uterine malignant mesodermal mixed tumors (UMMMTs), clear cell carcinomas (UCCs), and uterine serous carcinomas (USCs)—are aggressive malignancies that present with advanced disease and have high mortality rates. PIK3CA mutations are commonly found in endometrial cancers. The objective of the study was to characterize molecular alterations in the PIK3CA gene in these tumors.

Methods A total of 84 cases (20 UMMMTs, 18 UCCs, and 46 USCs) were selected from the surgical pathology files of Weill Cornell Medical College and Johns Hopkins Hospital. The diagnoses were confirmed by gynecologic pathologists (L.H.E. and A.Y.). DNA was extracted from paraffin-embedded tissue. Polymerase chain reaction was performed for mutational analysis. All the studies were performed in accordance with approved Institutional Review Board protocols.

Results Mutations in the PIK3CA gene were identified in 3 (15%) of 20 UMMMT, 3 (16.7%) of 18 UCC, and 10 (21.7%) of 46 USC cases. We report novel mutations in PIK3CA in uterine carcinosarcoma.

Conclusions A significant percentage of UMMMTs, UCCs, and USCs have mutations in PIK3CA. Further investigation is needed to develop targeted therapies for these aggressive uterine cancers.

  • Type II endometrial cancer
  • Serous
  • Clear cell
  • Carcinosarcoma
  • PIK3CA

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Footnotes

  • Supported by an NCI grant CA095427-09 (L.H.E.) and The Macy’s Foundation Grant (T.A.C.).

  • The authors declare no conflicts of interest.