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.