Characterization of human ovarian carcinomas in a SCID mouse model

This study characterizes a murine model which is promising for the study of the growth and natural history of ovarian cancer and for testing of new th erapies for its treatment. Intact portions of 20 different human ovarian ca ncer surgical specimens were implanted in over 60 severe combined immunodef icient (SCID) mice using techniques previously developed in our laboratory. Growth of xenografts was evaluated by gross examination and histopathologi c analysis. Confirmation of the human origin of the tumor outgrowth was obt ained using in situ hybridization analysis. By histological evaluation, all of the patients' tumors showed evidence of invasive growth in at least 1 o f the mice implanted with portions of each surgical specimen and these tumo rs remained morphologically similar to the parent tumors for a long period of time. Furthermore, 65% (13/20) of the xenografts grew rapidly enough (i. e., reached a diameter of 1-2 cm within 2-6 months) to allow passage to sub sequent SCID mice. Among the passaged xenografts, 3 eventually developed me tastases in a distribution pattern similar to that of naturally occurring o varian cancer and 2 developed ascites without evidence of further metastati c spread. Upon evaluation of sera from tumor-bearing mice, human antibodies presumably derived from immunoglobulin-secreting cells present in the orig inal tumor specimen were identified. In support of this, human B cells and plasma cells could be seen within the tumor xenograft for more than 6 month s following implantation. In summary, transplantation of surgical specimens from ovarian cancer patients into SCID mice results in an attractive model for the study of the natural history of ovarian cancer and may also be use ful for analysis or new experimental therapeutic approaches for the treatme nt of this disease. (C) 1999 Academic Press.