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abstract:
Evaluation of minimal disseminated disease in cryopreserved ovarian tissue from bone and soft tissue sarcoma patients
STUDY QUESTION What is the risk of finding malignant cells in cryopreserved ovarian tissue from sarcoma patients?
SUMMARY ANSWER Minimal disseminated disease (MDD) was not detected in frozen-thawed ovarian tissue from 26 patients by any of the sensitive
methods applied.
WHAT IS KNOWN ALREADY
In case of leukemia, the risk of malignant cell transmission through the
graft is well known and widely documented. However,
for bone cancer, like Ewing sarcoma or
osteosarcoma, only a small number of case reports, have been published.
These cancers
often affect prepubertal girls, in whom ovarian
tissue cryopreservation and transplantation is the only option to
preserve
fertility.
STUDY DESIGN, SIZE, DURATION
The presence of malignant cells in cryopreserved ovarian tissue from
patients with bone/soft tissue sarcoma was investigated
with disease-specific markers for each patient,
using immunohistochemistry (IHC), FISH and real-time quantitative RT-PCR
(qPCR),
with the original tumor serving as a positive
control.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Forty-eight sarcoma patients were enrolled in the study, 12 of whom
subsequently died. In each case, tissue from the primary
tumor was investigated in order to identify
markers (immunohistochemical and/or molecular) to analyze the ovarian
tissue case
by case. Ovarian tissue from osteosarcoma (n = 15), liposarcoma (n = 1) and undifferentiated sarcoma (n = 5)
patients could not be evaluated, as no specific markers were detected
by FISH or sensitive IHC in any of their primary
tumoral tissue. One patient with Li-Fraumeni
syndrome was also excluded from the study. IHC analyses were therefore
performed
on ovarian tissue from 26 patients and qPCR on
19. The primary tumors involved were Ewing sarcoma family of tumors (n = 14), rhabdomyosarcoma (n = 7), synovial sarcoma (n = 2), clear cell sarcoma (n = 2) and a malignant peripheral nerve sheath tumor (n = 1).
MAIN RESULTS AND THE ROLE OF CHANCE
MDD was not detected in any of the 26 analyzed samples using sensitive
techniques in this largest reported series, even from
patients who subsequently died and/or those who
presented with metastasis (11/26), hence the most aggressive forms of
bone
cancer. Indeed, anti-CD99 IHC and PCR performed
on patients presenting with Ewing sarcoma family of tumors (n = 14) was negative in all cases. In patients with soft tissue sarcoma (n = 12) primitive tumor markers were detected by IHC and were negative in ovarian tissue. PCR could only be performed in 6/12
of these patients, again proving negative.
LIMITATIONS, REASONS FOR CAUTION
Cryopreserved ovarian fragments to be transplanted cannot be tested, so
this analysis of malignant cells cannot guarantee
that all cryopreserved fragments will not
contain any disseminated disease. Moreover, molecular markers are not
readily available
for all types of tumors.
WIDER IMPLICATIONS OF THE FINDINGS
These results are reassuring regarding the risk of malignant cells in
the ovary for transplantation, as the study involves
a large series including different types of
sarcomas. We believe this will help clinicians in their patient
counseling for
fertility preservation and restoration.
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