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Detection of minimal disease in patients with solid tumors
1Institut für Immunologie, Ludwig-Maximilians-Universität München, Germany.
Abstract:
The detection and elimination of minimal systemic disease in patients with solid tumors is one of the main current topics in clinical oncology. The present review focuses, therefore, on new diagnostic approaches to identify minimal disease in peripheral blood, bone marrow, and lymph nodes of patients with epithelial cancer as the major type of solid tumors in Western industrialized countries. These approaches may be used to improve tumor staging and monitoring of adjuvant therapies, as well as to detect tumor cell contamination in autologous stem cell grafts. Most investigators have developed either immunocytochemical assays with monoclonal antibodies to a variety of epithelial-specific cytoskeleton and membrane antigens or molecular methods based on the extensive amplification of a specific (c)DNA sequence by the polymerase-chain reaction (PCR). In immunocytochemical assays, antibodies to cytokeratins can be regarded as the most specific and sensitive probes to detect isolated epithelial tumor cells in bone marrow and blood. Molecular methods are based on the detection of either mutations in oncogenes and tumor suppressor genes (e.g., ki-ras and p53 genes) or the mRNA expression of tissue-specific and tumor-associated genes. mRNA species targeted in these assays encode cytokeratins, prostate-specific antigen, prostate-specific membrane antigen, carcinoembryonic antigen, and polymorphic-epithelial mucin. To introduce the available methods into clinical practice, standardized protocols need to be developed and validated in multi-center studies.
Insights
Detecting minimal residual cancer is key in oncology. New immunocytochemical and molecular methods, like polymerase-chain reaction (PCR), identify epithelial tumor cells in blood and bone marrow for better staging and therapy monitoring.
Area of Science:
- Oncology
- Cancer Diagnostics
- Molecular Biology
Background:
- Minimal systemic disease detection is a critical challenge in solid tumor oncology.
- Epithelial cancers represent the predominant solid tumors in Western industrialized nations.
- Accurate detection aids in improving tumor staging and monitoring adjuvant therapies.
Purpose of the Study:
- To review novel diagnostic approaches for identifying minimal disease in epithelial cancers.
- To explore methods for detecting tumor cell contamination in autologous stem cell grafts.
- To highlight advancements in detecting minimal residual disease (MRD).
Main Methods:
- Immunocytochemical assays using monoclonal antibodies against epithelial-specific antigens.
- Molecular methods, including polymerase-chain reaction (PCR), for DNA/cDNA amplification.
- Detection of gene mutations (e.g., ki-ras, p53) and mRNA expression (e.g., cytokeratins, PSA).
Main Results:
- Antibodies to cytokeratins show high specificity and sensitivity for detecting epithelial tumor cells.
- Molecular methods target oncogenes, tumor suppressor genes, and tissue-specific/tumor-associated mRNA.
- Various epithelial markers are identified using immunocytochemistry and molecular techniques.
Conclusions:
- New diagnostic tools offer improved detection of minimal disease in epithelial cancers.
- Standardized protocols and multi-center validation are necessary for clinical implementation.
- Enhanced detection capabilities can refine cancer staging and therapeutic monitoring.