title: An orthotopic model of platinum-sensitive high grade serous fallopian tube carcinoma.
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, 5 mg/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.
authors.affiliation: Department of Obstetrics and Gynecology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. dineo.khabele@vanderbilt.edu
authors.forename: Dineo
authors.initials: D
authors.lastname: Khabele
authors.forename: Oluwole
authors.initials: O
authors.lastname: Fadare
authors.forename: Annie Y
authors.initials: AY
authors.lastname: Liu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wilson
authors.forename: Erika
authors.initials: E
authors.lastname: Wass
authors.forename: Kevin
authors.initials: K
authors.lastname: Osteen
authors.forename: Marta A
authors.initials: MA
authors.lastname: Crispens
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy* / Q000473:pathology*; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009367:Neoplasm Staging; D011230:Precancerous Conditions / Q000473:pathology; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin