Tools
Laboratory Evaluation of Tumor Biomarkers
Introduction
Tumor biomarkers are substances synthesized by cancer cells or other body cells in response to cancer and released into the circulation.[1] Tumor biomarkers vary widely in structure and may be simple molecules, such as catecholamines; well-characterized proteins, such as hormones, enzymes, or gene products; or heterogeneous glycoproteins or mucins, such as carbohydrate antigen 125 (CA-125), which may be quantified using antibodies. Several important tumor biomarkers, such as α-fetoprotein (AFP), carcinoembryonic antigen (CEA), and human chorionic gonadotropin (hCG), are oncofetal antigens present in the fetus, expressed at minute concentrations in healthy tissues but at high concentrations in some malignant neoplasms.[2]
Assays for tumor biomarkers are used in various clinical settings and are integral to many cancer diagnoses and management plans. Using various techniques, these biomarkers may be assayed in selected body fluids such as blood, urine, and pleural or peritoneal effusions. Assays of tumor biomarkers may aid in the screening and early diagnosis of malignant neoplasms, guide treatment decisions, monitor treatment response, assess disease progression, or detect cancer recurrence.[3] However, tumor biomarker assays have limitations and should not be used as standalone diagnostic tools.[4] The results of tumor biomarker assays are most effective when interpreted with clinical information, imaging studies, and pathological tissue examination to ensure a comprehensive assessment and facilitate an accurate diagnosis.
The ideal tumor biomarker is an inherently stable molecule with high specificity, sensitivity, accuracy, and reproducibility, enabling cost-effective screening, diagnosis, and prognosis. However, clinically employed tumor biomarkers do not possess all these characteristics. Most tumor biomarkers have limitations in specificity, sensitivity, or clinical utility, making their use in conjunction with other diagnostic tools essential for comprehensive evaluation and treatment of patients.[1][3][5]
Etiology and Epidemiology
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Etiology and Epidemiology
Cancer is not one disease but a group of diseases characterized by dysregulated cellular growth. Malignant neoplasms can infiltrate, invade, and destroy surrounding tissues.[6] Cancers are caused by genetic mutations that may be inherited or acquired through exposure to environmental carcinogens.[7] Carcinogens such as tobacco smoke, asbestos, ionizing and ultraviolet radiation, and infections are associated with malignant neoplasm development.[8]
Cancer is one of the leading causes of death worldwide, accounting for 10 million deaths yearly.[9] On average, 22.6% of women and 18.6% of men risk developing cancer before the age of 75 years.[10] In younger individuals, the most commonly encountered malignant neoplasms are hematological. However, in older individuals, breast, prostate, lung, and colorectal cancers are the most common.
These 4 malignant neoplasms comprise more than half of the cancer diagnoses worldwide. Cancer incidence is increasing globally due to an aging population, lifestyle changes, and environmental pollution. By 2050, the number of cancer cases is predicted to increase to 35 million based solely on projected population growth.
Bence Jones protein was the first tumor biomarker described in the literature.[11] Since then, many protein- and hormone-based tumor biomarkers have been described and introduced into clinical practice. More recently, proteomics and genomics technologies have enabled the analysis of various genetic and molecular tumor biomarkers using microarray techniques.
Specimen Requirements and Procedure
The National Academy of Clinical Biochemistry has established preanalytical quality guidelines for tumor biomarkers.[12] For example, serum assays should be collected in red-top containers. Other body fluids should be collected in fluid-specific containers.[13]
Chromosomal assessment of bone marrow requires 2 to 3 mL of bone marrow from the first pull of the repositioned needle during marrow extraction.[14] Whole blood is required for microarray techniques.[15] Immunohistochemistry requires approximately 1 mL of tissue, and the sample should be deparaffinized and rehydrated before staining.[16]
Samples should ideally be assayed immediately. Tissue or bone marrow samples for chromosomal assessment, fluorescent in situ hybridization, or microarray should not be frozen. Salivary contamination may cause falsely increased concentrations of CEA and carbohydrate antigen 19-9.[17] Specimens can be collected at any time of the day because diurnal variation is not a factor.
Specimens should always be collected before any invasive procedure, because tissue trauma may cause a transient release of tumor biomarkers into the circulation. For example, prostate-specific antigen (PSA) results increase following urinary catheterization and prostate biopsy, and CEA results increase after colonoscopy. Tumor biomarker assays should ideally be repeated after 2 to 3 weeks for additional diagnostic information.[18]
The commonly measured tumor biomarkers are generally stable. However, serum or plasma should be separated from the clot and stored at 4 °C in the short term, or at temperatures less than −30 °C as soon as possible. Relevant guidelines should be followed if available. For prolonged storage, specimens should be stored at −70 °C.[19] Heat treatments should be avoided, such as those used to deplete serum complement components or to inactivate HIV. Avoidance of heat treatments is particularly important for PSA and hCG assays, because these biomarkers may dissociate into their free α- and β-subunits at increased temperatures.[20]
Diagnostic Tests
Many malignant neoplasms have one or more tumor biomarkers that are routinely measured during diagnosis, management, and monitoring. Some of these malignancies and their respective biomarkers are listed in Table 1.
Table 1. Malignant Neoplasms and Related Tumor Biomarkers
| Malignancy | Related Tumor Markers |
|
Bronchogenic: Small cell carcinoma Adenocarcinoma Squamous cell carcinoma |
Neuron-specific enolase, progastrin–releasing peptide CEA Squamous cell carcinoma antigen, cytokeratin 19 fragment |
|
Ovarian: Epithelial Mucinous Nonepithelial |
CA-125 CEA Inhibin A and B |
| Colorectal adenocarcinoma |
CEA CA 19-9 Tissue plasminogen activator |
| Hepatocellular carcinoma | AFP |
| Pancreatic adenocarcinoma |
CA 19-9 CEA |
| Prostate adenocarcinoma |
PSA Prostatic acid phosphatase |
| Germ cell tumors |
hCG AFP Lactate dehydrogenase Placental alkaline phosphatase |
| Breast |
Cancer antigen 15-3 Carbohydrate antigen 27.29 Estrogen and progesterone receptors Human epidermal growth factor receptor 2 (HER2) Urokinase plasminogen activator Plasminogen activator inhibitor |
AFP, alpha-fetoprotein; CA, carbohydrate antigen; CEA, carcinoembryonic antigen; hCG, human chorionic gonadotropin; HER2, human epidermal growth factor receptor 2; PSA, prostate-specific antigen
Testing Procedures
Various assays can be used to assess tumor biomarkers. The most commonly used testing procedures include:
Enzyme Activity Assays
Most enzymatic tumor biomarkers are quantified using enzyme activity assays.[1] Enzymatic activity directly reflects biomarker concentration in the sample. These assays involve adding excess substrate and cofactors, then measuring the rate of product formation. Kinetic assays monitor substrate conversion at timed intervals for precise quantification. Common examples include alkaline phosphatase in prostate or liver metastases and lactate dehydrogenase in lymphomas or germ cell tumors. Please see StatPearls' companion reference, "Alkaline Phosphatase," for further information.
Immunoassays
Immunoassays are based on antigen–antibody interactions, where the biomarker serves as the antigen. Common methods include enzyme-linked immunosorbent assay, electrochemiluminescence immunoassay, chemiluminescence immunoassay, and radioimmunoassay. Many tumor biomarkers are quantified using these methods, including AFP, CEA, hCG, prolactin, calcitonin, and carbohydrate antigens.[21]
High-Performance Liquid Chromatography
High-performance liquid chromatography separates and quantifies analytes based on physical and chemical properties. In oncology, the test is primarily used to detect catecholamines and their metabolites in plasma and urine to diagnose neuroendocrine tumors. Modern high-performance liquid chromatography is often combined with mass spectrometry to enhance sensitivity and specificity, and to enable simultaneous detection of multiple tumor-related metabolites.[22]
Immunohistochemistry
Immunohistochemistry is a tissue-based immunoassay used to detect tumor biomarkers in solid tissue biopsies. Thin tissue sections are incubated with antibodies specific to the target antigen, and colorimetric or fluorescent secondary antibodies are used to visualize binding. Immunohistochemistry is commonly used to detect estrogen receptor, progesterone receptor, and HER2 in breast cancer, among other tissue-specific markers.[23]
Fluorescence In Situ Hybridization
Fluorescence in situ hybridization detects genetic alterations in tumor cells using fluorescently labeled DNA probes that hybridize to specific target sequences. Please see StatPearls' companion reference, "Molecular Genetics Testing," for further information. This test is applied to identify HER2 amplification, adenomatous polyposis coli (APC) mutations, and rat sarcoma (RAS) mutations, providing prognostic and therapeutic guidance.[24]
Polymerase Chain Reaction
Polymerase chain reaction amplifies specific DNA sequences to detect genetic mutations or gene fusions. This test is widely used in oncology to identify breakpoint cluster region–Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL1) fusions, Kirsten rat sarcoma viral proto-oncogene (KRAS), neuroblastoma RAS viral proto-oncogene (NRAS), and B-Raf proto-oncogene serine/threonine kinase (BRAF) mutations, as well as Erb-B2 receptor tyrosine kinase 2 (ERBB2) gene amplification (HER2), guiding targeted therapy and prognosis.[25]
Microarrays
Microarrays enable simultaneous evaluation of thousands of genes for expression, mutation, or copy-number changes. In oncology, they are used for genetic profiling of ovarian and colorectal cancers, leukemias, and metastatic tumors of unknown origin, facilitating personalized treatment planning.[26][27]
Next-Generation Sequencing
Next-generation sequencing enables high-throughput analysis of multiple genes, detecting mutations, copy number variations, and gene fusions. This test is applied for tumor profiling, identification of actionable mutations, and calculation of tumor mutational burden, guiding personalized therapy in solid and hematologic malignant neoplasms.[28]
Flow Cytometry
Flow cytometry is primarily used for immunophenotyping of cells and detecting minimal residual disease. Flow cytometry quantitatively analyzes cell-surface and intracellular biomarkers, aiding in diagnosis, prognosis, and therapy monitoring.[29]
Methylation Analysis
Methylation assays detect epigenetic changes in tumor DNA, such as promoter methylation of tumor suppressor genes. They are used for cancer diagnosis, prognosis, and predicting therapy response. Examples include O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in gliomas or septin 9 (SEPT9) methylation in colorectal cancer.[30][31]
Mass Spectrometry
Mass spectrometry provides high-sensitivity detection and quantification of proteins, peptides, and metabolites. This assay is particularly useful for targeted proteomics, measuring biomarkers (eg, thyroglobulin or insulin-like growth factor 1) that may be difficult to quantify by standard immunoassays due to antibody interference.[32]
Liquid Biopsy
Liquid biopsy analyzes tumor-derived material in blood or other body fluids. This test includes detecting circulating tumor DNA for real-time monitoring of tumor mutations and isolating circulating tumor cells or exosomes to assess metastatic potential and tumor protein cargo, providing a minimally invasive alternative to tissue biopsy.[33][34]
Spatial Profiling and Transcriptomics
These emerging techniques allow biomarker detection while preserving spatial tumor architecture. By mapping gene or protein expression within the tumor microenvironment, clinicians can better understand tumor heterogeneity and immune interactions, improving prognosis and therapy selection.[35][36]
Interfering Factors
Disadvantages of Tumor Biomarkers
Variations in sample collection, handling, storage, and assay techniques can alter the biomarker profile in a given sample. Standardization of the preanalytical and analytical variables may mitigate these variations. Very low concentrations of tumor biomarkers are often detected in early-stage tumors, necessitating a highly sensitive assay.[37] Tumor biomarkers also have inherent drawbacks and disadvantages, including:
- Lack of specificity: Some tumor biomarkers are produced by normal and cancerous cells, and levels are elevated in many noncancerous conditions. This lack of specificity can result in false-positive findings, potentially leading to unnecessary diagnostic procedures or treatment interventions.[2]
- Lack of sensitivity: Tumor biomarker levels may not be elevated in all patients with a specific cancer, particularly in the early stages of the disease. This lack of sensitivity can result in false-negative findings, in which biomarker concentrations fall within reference ranges despite the presence of cancer. False-negative results may delay the diagnosis and lead to missed opportunities for early intervention and treatment.[38]
- Biological variability: Individual patients can exhibit biological variability in tumor biomarker levels, making it challenging to establish universal reference ranges or cut-off values for diagnosis or monitoring.[39] Biological factors such as age, sex, genetics, and comorbidities can influence biomarker levels, leading to variations in results among individuals.
- Analytical variability: Variations in assay platforms, reagents, and laboratory techniques can contribute to analytical variability in tumor marker measurements. Inconsistent methods and a lack of standardization can affect the accuracy and reliability of results, hindering comparisons of data across laboratories or over time.[40]
- Limited diagnostic utility: Tumor biomarker assays are unsuitable as standalone diagnostic tools for cancer and should be used in conjunction with other diagnostic methods, such as imaging studies, biopsies, or clinical evaluations, to establish a comprehensive diagnosis.[2] Relying solely on tumor biomarker assays may lead to incomplete or inaccurate diagnostic conclusions.
Commonly Encountered Interferences
- High-dose hook effect: This effect is characterized by falsely low values at high tumor biomarker concentration and is commonly seen when assays are performed in patients for the first time.[41] The high-dose hook effect can be avoided by using solid-phase antibodies of higher binding capacity, performing the assay in 2 sample dilutions, and implementing proper wash steps.
- Specimen carryover: This interference is most commonly encountered when dealing with high-concentration markers in the assay.
- Interference from heterophilic or human antimouse antibodies: Samples from patients who have undergone monoclonal antibody therapy or have circulating anti-animal antibodies may return falsely high or low values.[42] Identifying the presence of interfering antibodies requires a high degree of clinical suspicion that a tumor marker result is incorrect; this clinical suspicion may be strengthened if pertinent clinical information is available. Once suspected, potential interference can be investigated by testing the specimen at various dilutions; retesting after treatment with a commercially available blocking agent; adding additional nonimmune mouse serum to the reaction mixture and reassessing; or reassessing the specimen using a different method from another manufacturer.[43] These results should be interpreted with caution.
- Pharmaceutical interference: Anticoagulants such as ethylenediaminetetraacetic acid might interfere with some assays.[44]
Results, Reporting, and Critical Findings
The reported results should include reference intervals specific to the employed method and derived from an appropriate healthy population.[45] If possible, the assay technique should be reported with the results. If a method or technique has changed, the laboratory should indicate whether the change would affect the interpretation of results. If methods are changed, a defined protocol should be followed, and the likely effect should be communicated.[3] Analyzing the previous specimen using the new method, or requesting another specimen to reestablish the baseline or confirm the trend in biomarker concentrations, may be required.[46]
Rather than interpreting a single value, observing the overall trend in biomarker concentration over time from interval testing is more likely to provide valuable insight into disease status. Graphical reporting can offer a clear and concise way to interpret the trend in biomarker concentrations over time.[1] Recording brief clinical information alongside laboratory data enhances the interpretation of results. Recommendations on the need for confirmatory specimens and the testing interval can also be included.
Reporting critical increases in tumor biomarker concentrations, while accounting for the test's analytical performance, biological variation, and individual reference intervals, contributes to earlier detection of relapse. The percentage increase or decrease should be defined; analytical and biological variation should be accounted for; the expected rate of change in benign and malignant conditions should be delineated; and the time between samples should be reported.[47] Differences in the magnitudes of biological variation in tumor markers contribute significantly to these percentages.[48]
The half-life of the tumor biomarker must be considered when interpreting test results. Before surgical intervention, use the biomarker's known half-life to estimate the time required for the level to decline to the reference range or an undetectable level.[49] If a quantitative decline in a tumor biomarker will be used to determine the likelihood of complete tumor resection, the biomarker should not be measured until at least 2 to 4 weeks postoperatively.[1]
The rate of decline may be affected by underlying comorbidities such as renal or hepatic dysfunction. For example, serum CEA often remains elevated in patients with underlying hepatic dysfunction due to inefficient hepatic metabolism of the biomarker.[50] Persistently elevated serum β-2 microglobulin levels are frequently noted in patients with acute and chronic renal disease; even the small-sized β-2 microglobulin molecule has difficulty passing through the injured glomerular apparatus.[51]
If appropriate for the specific malignant neoplasm, clinicians should consider ordering a panel of tumor biomarkers to improve diagnostic sensitivity and specificity.[1] Many malignant neoplasms have heterogeneous cellular composition and express multiple tumor biomarkers. Measuring multiple biomarkers is frequently required to achieve a sensitivity greater than 90%.[13]
Clinical Significance
Each tumor biomarker possesses some degree of clinical utility and correlates to one or several specific malignant neoplasms. Many tumor biomarkers are expressed to some degree in normal, healthy cells or tissues, and circulating biomarker levels can be affected by benign conditions. The sensitivity and specificity of each assay must be considered in the context of the patient's clinical condition.[39]
Many national and international guidelines address the selection and use of tumor biomarkers. The National Academy of Clinical Biochemistry, the European Group on Tumor Markers, the American Cancer Society, the National Comprehensive Cancer Network, and the National Institute for Health and Care Excellence have established recommendations regarding the use of tumor biomarkers based on the level of available evidence. The clinical significance of some commonly measured tumor biomarkers is described in Table 2.
Table 2. The Clinical Significance of Selected Tumor Biomarkers
| Tumor Biomarker | Family | Chemistry | Clinical Significance | Limitation |
| AFP | Oncofetal antigen | Glycoprotein is synthesized from the yolk sac and embryonic liver | Diagnosis and monitoring of hepatocellular carcinoma, hepatoblastoma, and germ cell tumors. Prognostic marker of germ cell tumor [3] | Elevated in pregnancy, neonates, benign liver diseases, and diseases of the gastrointestinal tract [52] |
| CEA | Oncofetal antigen | Glycoprotein isolated from fetal gastrointestinal tissue | Monitoring response to therapy and relapse of colorectal adenocarcinomas [53] | Serum levels in early-stage and poorly differentiated cancer are low and elevated in benign renal, liver, and lung diseases. Not specific to colorectal malignancy [53] |
| ALP | Enzyme | Enzymes of bone, placenta, small bowel, and biliary tract. Isoenzymes are more specific | Elevated in osteosarcoma, cholangiocarcinoma, and bony metastases [54] | Serum levels are elevated in normal pregnancy and benign diseases of bone, small bowel, and the hepatobiliary system [55] |
| Lactate dehydrogenase | Enzyme | An enzyme found in almost all body cells that interconverts pyruvate and lactate | Elevated in almost all malignancies due to its ubiquitous nature [56] | Elevated in many anemias and any disease characterized by cellular destruction |
|
Prostatic acid phosphatase |
Enzyme |
Glycoprotein dimer | Monitoring response to therapy and relapse of prostatic adenocarcinoma [57] | High serum levels are encountered in some lysosomal storage disorders and many benign prostatic diseases |
| Neuron-specific enolase | Enzyme | Dimer of the enzyme enolase, synthesized by neuroendocrine cells | Elevated in neuroblastoma, small cell lung cancer, and pancreatic adenocarcinoma | Delays in the assay should be avoided [58] |
| hCG | Hormone | Glycoprotein hormone is synthesized by placental syncytiotrophoblasts | Diagnosis, prognosis, and monitoring treatment response of gestational trophoblastic tumor and germ cell tumors [3] | Elevated in normal pregnancy [59] |
| Prolactin | Hormone | Anterior pituitary hormone | Pituitary adenocarcinoma | Diurnal variation is seen. Serum levels may be elevated due to benign pituitary prolactinomas and in response to many medications [60] |
| Calcitonin | Hormone | Mucin glycoprotein secreted by thyroid parafollicular C cells | Diagnosis and monitoring of medullary thyroid carcinoma | Falsely elevated in Zollinger-Ellison syndrome, pernicious anemia, and chronic renal disease [61] |
| Catecholamines and metanephrines | Hormone | Biogenic amines are produced by the adrenal gland and the sympathetic nervous system | Diagnosis and monitoring of neuroblastoma, pheochromocytoma, and paragangliomas [62] | Serum levels may be elevated in response to many medications, and normal diurnal variation is seen |
| Serotonin | Hormone | Biogenic amine | Diagnosis and monitoring of carcinoid tumors [63] | Levels may be elevated after consuming meat and fruits |
| PSA | Protein | Glycoprotein with serine protease activity that circulates free or bound to antichymotrypsin or macroglobulin | Screening, risk assessment, and monitoring for prostatic cancer [64] | Serum levels may be elevated in many benign prostatic diseases and after manipulation of the male lower genitourinary tract [65] |
| Cancer antigen 15-3 | Protein | Mucin glycoprotein | Used in conjunction with CEA for monitoring breast cancer. Used as a marker for treatment response | Elevated in benign and malignant breast, ovarian, and liver disease [58] |
| Carbohydrate antigen 19-9 | Protein | Lewis blood grouping glycolipid | An increase in pancreatic and hepatobiliary cancer. Monitoring pancreatic cancer following resection | Specimens contaminated with saliva may show high CA 19-9 values. Low or absent levels in patients who are negative for the Lewis blood group [17] |
| CA-125 | Protein | Mucin glycoprotein | Screening and monitoring ovarian epithelial carcinoma | CA-125 is also made by the pleurae, pericardium, and peritoneum, and will be elevated in benign diseases affecting those tissues [66] |
| β-2 microglobulin | Protein | Component of the major histocompatibility complex class I | Increased in chronic lymphocytic leukemia, multiple myeloma, and B-cell neoplasms [3] | May be elevated in acute and chronic renal disease and active HIV infection |
| Thyroglobulin | Protein | Glycoprotein dimer | Monitoring differentiated thyroid carcinoma [67] | Autoantibodies in many thyroid diseases falsely elevate serum thyroglobulin levels. |
| HER2 | Protein | Glycoprotein of the tyrosine kinase receptor family activation, which causes cell growth and proliferation | HER2 overexpression may be seen in breast, ovarian, and endometrial carcinoma [68] | Varying expressions in different areas of the tumor |
| Estrogen and progesterone receptors | Protein | Nuclear transcription factor and steroid receptor | Predicting responsiveness of breast cancer to antihormonal therapies [68] |
Biomarker expression changes over time |
| TP53 | Genetic marker | Tumor suppressor gene | The most commonly mutated gene in human cancer [3] | Elevated in the presence of some colon polyps |
| Retinoblastoma (RB) gene | Genetic marker | Tumor suppressor gene | Directly or indirectly mutated in almost all human cancers [69] | |
| BRCA1 and BRCA2 genes | Genetic marker | Tumor suppressor gene | Mutations predispose to many cancers in both sexes [3] | |
| APC gene | Genetic marker | Tumor suppressor gene | Hereditary nonpolyposis colonic, breast, and esophageal adenocarcinomas [58] | Elevated in the presence of some colon polyps |
| RAS | Genetic marker | Proto-oncogene | Mutations in RAS are found in most human cancers [70] | Mutations are almost ubiquitous and complex |
|
Cellular myelocytomatosis protooncogene c-MYC |
Genetic marker | Proto-oncogene | T-cell and B-cell lymphomas, small cell lung cancer. Used to identify a high-risk population [71] | Expression varies across tumor types |
| B-cell lymphoma 2 (BCL2) gene | Genetic marker | Oncogene promoting cell survival | Found in leukemia and lymphoma. Presence indicates resistance to chemotherapy [72] |
Quality Control and Lab Safety
The testing laboratory is responsible for implementing stringent quality control measures to ensure the accuracy and reliability of the test. Assays should be validated before clinical use to ensure accurate and relevant reports. Recommended intra-assay and inter-assay variability are less than 5% and less than 10%, respectively. Some newer techniques may perform significantly better but may be less precise.[12]
Aspects of quality control, such as internal and proficiency testing, should be implemented. The quality control specimen should mimic serum, and multiple levels can be used to cover the concentration range, including the decision limits. Negative and low-positive controls should be included.[73] The number of internal quality control samples to run for marker assay validation depends on the testing frequency. The samples should be checked frequently for assay interferences. During tumor marker assay, calibration and daily maintenance should be conducted before running quality control samples.[74]
Erroneous reporting should be avoided when an assay fails to meet the objective acceptance criteria. These criteria should be predefined and based on standardized measurements such as the Westgard criteria. The number of internal quality control specimens included per run should be sufficient to identify an unacceptable run with a probability appropriate to the clinical application.[75]
Given the long-term monitoring of cancer care, assay stability should be ensured over prolonged periods. Laboratories should have procedures and acceptance criteria for assessing lot-to-lot variation that may adversely affect clinical outcomes.[76] Quality control material not provided by the method manufacturer is preferable; kit controls may give an overly optimistic impression of performance because they are unlikely to be commutable with patient serum. At least 1 authentic serum matrix control from an independent source should be included in addition to any quality control materials provided by the method manufacturer.[74]
Proficiency testing specimens should be commutable with patient specimens to ensure valid between-method comparisons.[77] Concentrations should be assessed over the working range and include evaluations of linearity across dilutions, baseline security, and stability of results over time. The proficiency testing provider is responsible for ensuring specimen stability in transit.
The target values, usually consensus means for heterogeneous analytes, should be accurate and stable, as demonstrated by assessing their accuracy, stability, and linearity on dilution.[78] When performing tumor biomarker assays, clinicians and laboratory staff should adhere to standard laboratory safety practices, including the use of personal protective equipment, proper handling and disposal of biohazardous materials, and the maintenance of a clean work environment. Staff should follow equipment maintenance and calibration protocols and receive training in emergency procedures to promote a safe and efficient laboratory environment.[79]
Enhancing Healthcare Team Outcomes
Tumor biomarker assessment requires a multifaceted and interprofessional approach to ensure accurate testing, appropriate interpretation, and optimal integration into patient care. Laboratory professionals with expertise in tumor biomarker assays play a critical role in selecting appropriate tests for specific cancers, establishing clinically relevant cutoff values, and monitoring biomarker trends over time. Their technical skill ensures the reliability and validity of results, which form the foundation for effective clinical decision-making.[80]
Clinicians and pharmacists apply evidence-based strategies to interpret tumor biomarker data, determine clinical utility, and guide personalized treatment plans. Ethical principles are essential when discussing test results with patients, including transparent communication about limitations, uncertainties, and potential implications for treatment choices, while respecting patient autonomy.[81] Genetic counselors further support this process by helping patients and families navigate the implications of germline mutations discovered during biomarker profiling.
A central component of this collaboration is the molecular tumor board. Molecular tumor boards are interprofessional groups of oncologists, pathologists, bioinformaticians, pharmacists, and geneticists who meet to review complex genomic and biomarker profiles. The molecular tumor board serves as a formal platform to translate high-throughput data, such as next-generation sequencing results, into actionable clinical strategies, identifying specific clinical trials or targeted therapies tailored to the individual's tumor biology that a single clinician might not identify on their own.[82]
Patient safety is a priority at all stages, encompassing proper specimen collection, handling, storage, and data confidentiality to minimize the risk of errors and contamination. Effective interprofessional communication and coordination among clinicians, pathologists, laboratory technicians, nurses, and other health care professionals ensures timely results, accurate interpretation, and seamless integration of biomarker data into clinical care.[83] By fostering collaboration through structures like the molecular tumor board, defining roles and responsibilities, and implementing structured care processes, the interprofessional team enhances patient-centered care, diagnostic accuracy, treatment planning, and overall patient outcomes, while strengthening team performance in oncology practice.
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