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Int J Clin Exp Pathol 2012;5(1):37-45

Original Article
An orthotopic model of platinum-sensitive high grade serous fallopian tube carcinoma

Dineo Khabele, Oluwole Fadare, Annie Y. Liu, Andrew J. Wilson, Erika Wass, Kevin Osteen, Marta A. Crispens

Department of Obstetrics and Gynecology, Department of Cancer Biology, Department of Pathology, Vanderbilt-Ingram Cancer Center,
Vanderbilt University School of Medicine, Nashville, TN, USA

Received December 6, 2011; accepted December 15, 2011; Epub January 1, 2011; published January 15, 2012

Abstract: Fallopian tube carcinoma (FTCA) is a very rare cancer type, but may be a useful platform for investigating high grade serous tumors
of the pelvis that originate from a serous tubal intraepithelial carcinoma (STIC) precursor. Metastatic tumors from a patient diagnosed with
Stage IIIC high grade serous FTCA (P0) were transplanted via intraperitoneal (IP) injection into a small cohort of mice (passage, P1). Patient
information was obtained from the medical record. Tumors were grown, harvested and re-implanted or archived through P3. The P3 cohort was
treated with saline (n= 8) or cisplatin, 5mg/kg (n=8), weekly for 4 weeks. After sacrifice, tumors from each passage and treatment group were
passaged further, frozen or paraffin embedded. The patient underwent optimal cytoreductive surgery for Stage IIIC high grade serous FTCA in
the presence of a STIC. The FTCA, areas of STIC and normal appearing FT stained positive for p53, PAX8, pH2AX and mib-1. The patient
remained in remission 9 months after platinum-based chemotherapy. IP tumor propagation was readily achieved up to P3 in the mice. Similar
to the patient, orthotopic tumors were identified along peritoneal and mesenteric surfaces. Tumor histopathological and molecular features
were confirmed and maintained through P3.  The P3 cisplatin-treated mice had fewer tumor implants, higher levels of pH2AX and lower levels
of mib-1 expression compared to controls. This orthotopic model of platinum sensitive high grade serous FTCA is a viable platform to study the
biology and treatment of FTCA and other STIC-related pelvic serous carcinomas. (IJCEP1112003).

Keywords: Fallopian tube carcinoma, pelvic serous carcinoma, STIC, orthotopic model

Address all correspondence to:
Dineo Khabele, MD
Department of Obstetrics and Gynecology
Division of Gynecologic Oncology
Vanderbilt University Medical Center
B1100 Medical Center North
Nashville, TN 37232, USA.
Tel: (615) 322-2114; Fax: (615) 343-8403
E-mail: dineo.khabele@vanderbilt.edu