ORIGIN OF TUMORS

ORIGIN OF TUMORS IN SOLID ORGAN TRANSPLANT PATIENTS IDENTIFIED BY PCR-SSP BASED METHODOLOGY.
AL Lobashevsky, JE Townsend, RW Senkbeil, MH Deierhoi and JM Thomas, Tissue typing laboratory, UAB hospital, Birmingham, Al 35294.

Posttransplantation lymphomas and lymphoproliferative disorders (PLTD) are the common complication in solid organ and bone marrow recipients. Epstein-Barr virus (EBV) infection and heavy immunosuppressive therapy have been shown associated with increased risk of PLTD. Reduction or discontinuation of immunosuppressive therapy is the initial step in treatment of PLTD. However, this approach increases the risk of graft rejection. For that reason, the detection of tumor origin is a critical issue in monitoring of these patients. Here we report three cases of PLTD in lung and two kidney recipients. Pathology report and flow cytometric analysis of tumor tissues confirmed the development of B cell lymphoma in patients; one kidney recipient had carcinoma. Genomic DNA was extracted from the peripheral blood and tumor tissue. Donors and recipients were typed for HLA-A, B, Cw by standard CDC method using commercial monoclonal trays and for HLA-DR and DQ by PCR-SSP high resolution technique. All patients received their organs from cadaveric donors and had at least one HLA-DR antigen match. Tumor tissue was typed by PCR-SSP for HLA-DR and DQ regions. Tumor origin was judged on the basis of donor or recipient class II allele(s) in the tissue. Only host genotype was found in lung and one kidney recipient. However, both donor and recipient alleles were detected in the 2^nd renal patient. This same patient had B cell lymphoma of donor and recipient origin and was also unique in having an EBV positive status. These findings explain the presence of both donor and recipient genotypes in the tumor. Immunocompromized status of this patient, in association with EBV infection, facilitated tumor development. On the other hand, donor passenger leukocytes stuck to the graft endothelium could have been targets for the patient’s EBV and given the rise to B cell lymphoma of mixed origin. We observed no false positive reactions or unusual allelic combinations. All patients are still alive, have their grafts, and receive immunosuppressive drugs. The EBV positive kidney patient’s graft was removed 5 years after transplantation because of tumor growth. Our data demonstrate that tumor origin in solid organ recipients can be detected with a high degree of reliability using PCR-SSP high resolution typing. In addition, an EBV positive status of kidney recipient may be considered as another risk factor. This information is important in making decisions on immunosuppressive drug withdrawal/reduction and/or immunotherapy with autologous lymphocyte-activated killer (LAK) cells in cases of donor origin tumors.