Technical aspects of minimal residual disease detection in carcinoma patients

The burden of occult malignant cells which remains after a course of treatm ent that has resulted in clinical remission is referred to as minimal resid ual disease (MRD). MRD is increasingly considered as a determinant of local or systemic recurrence in cancer patients. During the last 20 years, metho ds for the detection of rare cancer cells have evolved from mere cytomorpho logical investigations to a variety of immunological and molecular assays. Since surgical therapy remains the best treatment option for cancer patient s with resectable tumors, the first question to address is whether the remo val of the tumor was complete or some cancer cells remained from the tumor at the primary site. Several tumor-associated DNA alterations have been ide ntified to solve this diagnostic problem. Assays detecting tumor-associated DNA alterations have been applied to resection margins and body fluids suc h as bronchoalveolar lavage, sputum, urine, pancreatic juice, colonic lavag e, and stool. Due to the higher sensitivity of immunocytochemical and rever se-transcriptase polymerase chain reaction (RT-PCR)-based assays, the secon d question to be addressed is whether systemic hematogenous or lymphatic sp read of cancer cells occurred. Disseminated cancer cells have been detected in bone marrow aspirates, peripheral blood, and lymph node biopsies, and c ancer cell dissemination is regarded as a relevant and independent prognost ic factor. Thus, sensitive techniques for the detection of MRD are likely t o guide indications for surgical or adjuvant therapy protocols in clinical oncology. However, since many of the assays for the detection of MRD are co mplex, and results are influenced by a variety of technical aspects, the ma jority of diagnostic applications have not yet been sufficiently standardiz ed. Consequently, quality control and reproducibility of minimal disease de tection assays remain unsolved problems. Therefore, well controlled collabo rative studies are urgently required to evaluate indications and diagnostic standards for these assays. This review summarizes technical aspects and t heir implications for the clinical application of presently available assay s for MRD detection in carcinoma patients. (C) 2001 Wiley-Liss, Inc.