Establishment of subrenal capsule xenografts of primary human ovarian tumors in SCID mice: potential models.
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.
Lee
Cheng-Han
CH
Department of Pathology, Genetic Pathology Evaluation Centre of the Prostate Centre, Vancouver General Hospital, BC Cancer Agency and University of British Columbia, Vancouver, BC, Canada V5Z 4E6.
Xue
Hui
H
Sutcliffe
Margaret
M
Gout
Peter W
PW
Huntsman
David G
DG
Miller
Dianne M
DM
Gilks
C Blake
CB
Wang
Y Z
YZ
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000276:immunology / Q000473:pathology*; D013370:Subrenal Capsule Assay; D014183:Transplantation, Heterologous