RESEARCH ARTICLE Establishment of a Patient-Derived Orthotopic Xenograft (PDOX) Model of HER- 2-Positive Cervical Cancer Expressing the Clinical Metastatic Pattern

Squamous cell carcinoma of the cervix, highly prevalent in the developing world, is often metastatic and treatment resistant with no standard treatment protocol. Our laboratory pio-neered the patient-derived orthotopic xenograft (PDOX) nude mouse model with the tech-nique of surgical orthotopic implantation (SOI). Unlike subcutaneous transplant patient-derived xenograft (PDX) models, PDOX models metastasize. Most importantly, the metas-tasis pattern correlates to the patient. In the present report, we describe the development of a PDOX model of HER-2-positive cervical cancer. Metastasis after SOI in nude mice includ-ed peritoneal dissemination, liver metastasis, lung metastasis as well as lymph node metas-tasis reflecting the metastatic pattern in the donor patient. Metastasis was detected in 4 of 6 nude mice with primary tumors. Primary tumors and metastases in the nude mice had histo-logical structures similar to the original tumor and were stained by an anti-HER-2 antibody in the same pattern as the patient’s cancer. The metastatic pattern, histology and HER-2 tumor expression of the patient were thus preserved in the PDOX model. In contrast, subcu-taneous transplantation of the patient’s cervical tumors resulted in primary growth but not metastasis