Establishment of subrenal capsule xenografts of primary human ovarian tumors in SCID mice: potential models

Abstract

Objective: To evaluate subrenal capsule xenografting of primary ovarian tumor tissues in mice for development of new ovarian cancer models.

Methods: Pieces (1 x 3 x 3 mm) of ovarian tumor specimens from patients were meticulously grafted under renal capsules of female NOD/SCID mice within 2 h of surgical removal. Tumor types included papillary serous adenocarcinomas, borderline and benign mucinous cystadenomas, granulosa cell tumors, a serous borderline tumor and a grade 3 mixed surface epithelial tumor of transitional and undifferentiated types. After 1-2 months, grafts were retrieved for comparison with original tissues. Hematoxylin and eosin (H&E) and immunohistochemical staining was carried out using tissue micro-arrays and CEA, B72.3, WT-1, OC125, keratin, inhibin, CK7, CK20, Cam5.2, and MIB-1 as markers.

Results: Tumor tissue engraftment rate was > 95%. Comparison of donor and post-graft tissues showed highly similar histopathological features; 91 +/- 5% concordance in immunostaining indicated major preservation of immunophenotypes in the xenografts for 30-60 days. There was a small, but significant, increase in MIB-1 proliferative index in xenografts compared to original specimens.

Conclusions: Subrenal capsule xenografts of primary human ovarian tumors in SCID mice can retain major histopathological and immunohistochemical characteristics of the original tissues. The achievable, consistently high engraftment rate allows use of such xenografts as tools for studying a wide range of ovarian tumors, including granulosa cell tumors and benign, borderline, and malignant surface epithelial neoplasms. Potential applications include preclinical testing of patients' tumor responses to various chemotherapeutic regimens, evaluation of novel therapeutic agents, analysis of tumor progression at cellular and molecular levels, and identification of new therapeutic targets.