Evaluation of quantitative polymerase chain reaction markers for the detection of breast cancer cells in ovarian tissue stored for fertility preservation

Capsule:
The molecular detection of MGB-1, GCDFP-15, and MGB-2 in ovarian tissue possibly increases the safety of cryopreserved ovarian tissue transplantation for restoring fertility in breast cancer survivors.

Authors:
Laurence Bockstaele, Ph.D., Selma Boulenouar, Ph.D., Géraldine Van Den Steen, B.Sc., Julie Dechène, B.Sc., Sophie Tsepelidis, M.D., Ligia Craciun, Ph.D., Jean-Christophe Noël, M.D., Ph.D., Isabelle Demeestere, M.D., Ph.D.

Volume 104, Issue 2, Pages 410-417

Abstract:

Objective:
To develop molecular tools increasing the sensitivity of breast cancer micrometastases detection within ovarian tissue cryopreserved for fertility preservation.

Design:
Expression of breast markers was evaluated by quantitative polymerase chain reaction in ovarian tissue from patients with benign or cancerous diseases. Suspected tissues were long-term xenografted into mice.

Setting:
Academic research institute.

Patient(s):
Patients undergoing a fertility preservation procedure.

Intervention(s):
Ovarian tissue was processed for RNA extraction and quantitative polymerase chain reaction analysis. Cryopreserved ovarian cortex from patients with breast cancer or benign disease was grafted for 6 months into severe combined immunodeficiency mice.

Main Outcomes Measure(s):
Predictive values of mammaglobin 1 (MGB-1), gross cystic disease fluid protein-15 (GCDFP-15), small breast epithelial mucine (SBEM), and mammaglobin 2 (MGB-2) to detect breast cancer cells in ovarian tissue, and the potential development of cancerous disease after xenograft of ovarian cortex from breast cancer patients.

Result(s):
MGB-1 and GCDFP-15 presented the highest predictive values to detect breast cancer micrometastases in the ovarian cortex, with an efficiency reaching 100% and 77%, respectively. The MGB-2 assay resulted in a high false-positive rate (47%) in the ovarian cortex but could be used to detect breast cancer cells in ovarian medulla. MGB-1 was detected in three of five ovarian cortex samples from early-stage breast cancer patients but not in the ovarian tissue from advanced breast cancer patients (none of 10). None of the mice grafted with ovarian tissue expressing these markers developed cancerous disease.

Conclusion(s):
MGB-1, GCDFP-15, and MGB-2 can serve as molecular markers for the detection of breast cancer micrometastases within the ovarian tissue of breast cancer patients. However, the clinical relevance of such a highly sensitive assay must be further investigated.

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