Cancer could return unless stored ovarian tissue undergoes adequate testing before re-implantation

Cancer patients who have been successfully treated for their disease face the prospect of its return if stored ovarian (or testicular) tissue is transplanted back into their bodies without adequate checks, according to researchers at two university hospitals in Israel.

Writing in Europe’s leading reproductive medicine journal, Human Reproduction, today, the researchers say that hundreds of cancer patients worldwide have ovarian tissue and, in some cases, testicular tissue frozen in the hope of being able to have children after their cancer treatment has finished; but they warn that few fertility centres have the skills and use the technology needed to check the tissue for residual cancer cells, making it possible for the original cancer to re-infect the body when the tissue is re-implanted to restore the patients’ fertility.

“The interest in ovarian tissue storage as a real option for preserving fertility in cancer patients has increased. However, genuine concerns regarding the possible recrudescence [re-appearance] of the primary disease following re-implantation of stored ovarian tissue with malignant cells exist,” write the authors.

The first author of the report, Dr Dror Meirow, said: “We think it’s vitally important to raise awareness amongst cancer patients, fertility specialists, oncologists and haematologists. There are few fertility centres in the world with the expertise and the technology to run the types of tests on tissue that are needed to detect residual cancer.

“However, not every reproductive service that has surgical skills and freezing facilities can be safely responsible for ovarian tissue cryopreservation. We suggest that these centres should store tissue for future investigation, and samples can be shipped to specialist centres for analysis.”

Dr Meirow, who leads the fertility preservation programme in the IVF Unit at Chaim Sheba Medical Center, Tel Hashomer (headed by Professor Jehoshua Dor), carried out the research with Professor Dina Ben Yehuda, director of the Hematology Division at Hadassah University Hospital, Jerusalem. Dr Meirow said that fertility centres with close connections to cancer and haematological centres should be able to work together in order to adopt the correct methods for checking stored tissue.

Before collecting tissue from the 58 young women in this study, Dr Meirow and his colleagues used various imaging methods (sonography, CT and PET scans) to look for cancer in the pelvis and ovaries of the patients; the women were about to receive chemotherapy for haematological cancers such as Hodgkin’s lymphoma, non-Hodgkin’s lymphoma and leukaemia, between 1997 and 2007. They found cancer in the pelvic area of two patients, and therefore ovarian tissue was not harvested. They collected tissue from the other 56 patients and, in addition to freezing strips for future transplantation; they also froze a smaller piece of ovarian tissue separately for each patient. They planned to use these extra strips for future checks for the presence of cancer cells, using the most modern methods that would be available at the time the tissue was thawed and prepared for transplantation.

When the ovarian tissue was thawed, they used several different methods to detect minimal residual disease:

-- Histological evaluation (close examination of thin strips of tissue)
-- Immunohistochemical staining (using antibodies to detect abnormal cells)
-- PCR (polymerase chain reaction, which amplifies sections of DNA) and real-time PCR to detect molecular markers that would indicate the presence of cancer cells.

The results were compared with the same tests carried out on the patients’ diseased tissue to check that the tests were capable of detecting cancer when it was known to be present.

None of the tests detected minimal residual disease in ovarian tissue for any of the patients, with one exception: modern highly sensitive real-time PCR detected cells in one CML patient where previous tests had not detected any sign of cancer, and so ovarian tissue transplantation was not carried out.

Dr Meirow said: “For this research we concentrated on haematological malignancies, which are common in young patients, but we are working also on solid tumours. Tumour cells of haematological cancers do not often form clumps of cells, which are easier to detect. Therefore, it is highly important to identify single cancer cells among hundreds of thousands of normal cells.

“It is important to use the method and the specific probe that is suitable for each patient, and with this research we had a positive control test from the tumour itself.”

The authors suggest that, as methods for detecting cancer cells are improving all the time and ovarian tissue can be stored for more than ten years, tests to detect residual disease should be carried out just before transplantation rather than at the time of collection. To do this, it is necessary to freeze smaller piece of ovarian tissue separately for minimal residual disease investigation.

Dr Meirow said: “Following our pioneer report in 2005 on pregnancy and delivery post transplantation of ovarian tissue, the next step is to inform patients about the increasing success of ovarian tissue transplantation, to continue to improve the success of ovarian tissue transplantation, but also to call on fertility centres that store ovarian tissue to look for minimal residual disease and to start freezing tissue now for future investigation. All of this holds true for testicular tissue too, although we are not so advanced in successfully removing, storing and transplanting testicular tissue as we are with ovarian tissue.”

Citation: Searching for evidence of disease and malignant cell contamination in ovarian tissue stored from hematologic cancer patients. Human Reproduction Vol.23, Issue 5. doi:10.1093/humrep/den055.

Source: European Society for Human Reproduction and Embryology

Related stories:

Overcoming Drug Resistance—Nanoparticles Trigger Built-In Cell-Death Signal
One of the most vexing problems in treating cancer is the propensity of tumors to develop resistance to a wide range of anticancer drugs. Over 70 percent of ovarian cancer patients, for example, have drug-resistant tumors at the time of their initial diagnosis, and virtually all patients who relapse have drug-resistant tumors.
Glypican-3 gene function in regulating body size helps inform novel cancer treatments
In a leading study that has implications for the development of novel therapies for a number of breast, lung and ovarian cancers that have lost the expression of a gene called glypican-3 (GPC3), Sunnybrook researchers have discovered how the loss of the GPC3 gene induces overgrowth through certain growth factors such as Sonic Hedgehog which stimulate cancer growth.
Researchers identify new cell targets for preventing growth of breast and other tumors
Researchers at the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill have discovered new targets for cancer treatment aimed at blocking a key step in tumor progression.
Replacing absent microRNAs could make tumors less invasive, more treatable
One group of small, non-coding RNA molecules could serve as a marker to improve cancer staging and may also be able to convert some advanced tumors to more treatable stages, report a University of Chicago-based research team in the April 1, 2008, issue of the journal Genes & Development.
Recurrent low-grade carcinoma of the ovary less responsive to chemo than more common ovarian cancers
Tampa, Fla.- Recurrent low-grade serous carcinoma, a rare type of ovarian cancer, is less sensitive to chemotherapy and therefore more difficult to treat than more common high-grade ovarian cancers, according to researchers from The University of Texas M. D. Anderson Cancer Center. The findings were reported at the Society of Gynecologic Oncologists 39th Annual Meeting on Women's Cancers.
Study finds thalidomide shows promise for treatment of recurrent ovarian cancer
Thalidomide, a drug blamed in the 1950s for causing birth defects, is now showing promise as a safe and effective treatment for women with recurrent ovarian cancer, according to a study led by a University of Minnesota Cancer Center researcher.
Taking the fight against cancer to heart
Hormones produced by the heart eliminated human pancreatic cancer in more than three-quarters of the mice treated with the hormones and eliminated human breast cancer in two-thirds of the mice, according to researcher David Vesely, a doctor at the James A. Haley Veterans Hospital in Tampa and a professor at the University of South Florida (USF).
BRCA1 mutation linked to breast cancer stem cells
A new study may explain why women with a mutation in the BRCA1 gene face up to an 85 percent lifetime risk of breast cancer. Researchers from the University of Michigan Comprehensive Cancer Center found that BRCA1 plays a role in regulating breast stem cells, the small number of cells that might develop into cancers.

News discussion:

Medicine & Health news