RT-PCR-Based Detection of Occult Disseminated Tumor Cells in Peripheral Blood and Bone Marrow of Patients with Solid Tumors: An Overview


a Address for correspondence: A. Zippelius, Medizinische Klinik III, Bone Marrow Transplantation Unit, Klinikum Groβhadern, Marchioninistraβe 15, D-81377 München, Germany. Alfred.Zippelius@T-Online.de


Abstract: Despite recent progress in early detection and local curative therapy, patients with primary epithelial cancer quite frequently relapse with incurable metastasis. Early disseminated tumor cells that may be seminal for distant failure and are undetectable by current diagnostic methods have been identified by immunocytochemical techniques in bone marrow of cancer patients using monoclonal antibodies against cytokeratins. Recently, promising new molecular approaches, namely, reverse transcriptase-polymerase chain reaction (RT-PCR) assays, have been suggested as a potential technique for the detection of minimal residual tumor burden by targeting mRNA transcribed from epithelial genes in bone marrow, peripheral blood, or lymph nodes. Several studies using RT-PCR thus far indicate a highly sensitive and specific staging tool, although the prognostic value is still controversial. However, limitations may arise from ectopic expression of marker mRNA in hematopoietic cells and deficient expression in circulating tumor cells. The present review focuses on the relevant literature and demonstrates the range of current applications of RT-PCR-based assays for detecting disseminated tumor cells in peripheral blood and bone marrow of patients with solid tumors. We will both summarize technical evaluations of published molecular approaches and discuss the widely disparate results on PCR findings in clinical studies.