What laboratory tests are used to detect different types of cancer?

Laboratory Tests for Cancer Detection

Laboratory testing for cancer detection varies significantly by cancer type, with most tests used for diagnosis, prognosis, and treatment selection rather than screening, as they generally lack sufficient sensitivity and specificity for population-based early detection. 1

Cancer-Specific Laboratory Testing Approaches

Lung Cancer

• Molecular testing is mandatory for all patients with lung adenocarcinoma to guide targeted therapy selection 2
• Test for EGFR mutations, ALK rearrangements, ROS1 rearrangements, BRAF V600E mutations, PD-L1 expression, and NRAS mutations using next-generation sequencing (NGS), real-time PCR, or fluorescence in situ hybridization (FISH) 2
• Specimens with as little as 20% tumor cells are acceptable for molecular testing 2
• Cell blocks or cytology smear preparations are suitable specimens 2
• Do not use EGFR expression by immunohistochemistry or EGFR copy number analysis to select patients for EGFR-targeted therapy 2
• Immunohistochemistry panel includes TTF-1 (positive in ~60% of lung adenocarcinomas), napsin A, cytokeratin 7, and SMARCA4 for TTF-1-negative cases 2

Colorectal Cancer

• Test all colorectal adenocarcinomas for KRAS, NRAS, and BRAF mutations to predict response to anti-EGFR antibody therapy (cetuximab, panitumumab) 2, 1
• Perform DNA mismatch repair (MMR) testing or microsatellite instability (MSI) testing on all newly diagnosed colorectal cancers for Lynch syndrome screening and immunotherapy eligibility 2, 1
• Immunohistochemistry for MMR proteins (MLH1, MSH2, MSH6, PMS2) is the preferred initial approach 2
• Test for MLH1 promoter methylation if MLH1 protein is absent to distinguish Lynch syndrome from sporadic cases 2
• Carcinoembryonic antigen (CEA) is used for monitoring therapy and surveillance, not diagnosis 3
• Fecal occult blood testing (FOBT) or fecal immunochemical test (FIT) is the only biomarker-based screening test proven to reduce colorectal cancer mortality 1, 4

Breast Cancer

• Test all invasive breast cancers for estrogen receptor (ER), progesterone receptor (PR), and HER2 status by immunohistochemistry and/or FISH 2, 1
• HER2 testing identifies patients likely to respond to trastuzumab (Herceptin) 3
• ER/PR status predicts response to hormone therapy 3
• Oncotype DX (21-gene expression assay) provides prognostic information and predicts chemotherapy benefit in ER-positive, HER2-negative, node-negative breast cancer 2, 1
• PIK3CA mutation testing via cell-free DNA is FDA-approved for treatment selection 5
• GATA3 and SOX10 immunohistochemistry help identify breast cancer as primary site in cancer of unknown primary 2

Prostate Cancer

• Prostate-specific antigen (PSA) is widely used but its value in reducing mortality from screening remains unclear 3, 4
• Immunohistochemistry for PSMA and/or NKX3.1 identifies metastatic prostate cancer in males with cancer of unknown primary 2

Ovarian Cancer

• CA-125 is used for monitoring therapy response, not for screening or diagnosis 3
• CA-125 combined with transvaginal ultrasound has been evaluated for screening but has not demonstrated mortality reduction 4

Germ Cell Tumors

• Alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) are essential for diagnosis, prognosis, and monitoring of non-seminomatous germ cell tumors 3
• These markers have high clinical utility for treatment monitoring 3

Hepatocellular Carcinoma

• AFP screening in high-risk patients (chronic hepatitis B or C, cirrhosis) can detect early disease 4

Neuroendocrine Tumors

• Synaptophysin and/or INSM1 immunohistochemistry identifies neuroendocrine differentiation 2

Cancer of Unknown Primary Workup

When evaluating metastatic cancer without identified primary:

Initial Immunohistochemistry Panel

• Broad-spectrum cytokeratin (AE1/AE3, OSCAR) for epithelial origin 2
• CD45 for hematologic malignancy 2
• SOX10 and/or S100 for melanoma 2
• If all three are negative, consider mesenchymal/sarcoma origin 2

Carcinoma Subtyping

• CK7 and CK20 staining patterns provide clues to primary site 2
• For males: PSMA and/or NKX3.1 to rule out prostate cancer 2
• For females: GATA3 for breast cancer, SOX10 for triple-negative breast cancer 2

Liver Metastases Panel

• CK7, CK20, CDX2, and TTF-1 (plus GATA3/SOX10 in women) screen for breast, lung, gastrointestinal, and pancreaticobiliary primaries 2
• SATB2 positivity is fairly specific for lower GI origin 2
• At least 80% of colorectal cancers show CK7-negative, CK20-positive, CDX2-positive pattern 2

Critical Testing Requirements

Laboratory Standards

• All molecular testing used for patient management must be performed in a CLIA-certified laboratory 2
• Laboratories must validate assays and participate in proficiency testing at least semiannually 2

Specimen Handling

• Formalin-fixed paraffin-embedded (FFPE) tissue is the standard specimen type 2
• Cytology preparations are increasingly accepted 2
• Procure sufficient tissue for molecular, biomarker, and histologic testing when performing minimally invasive procedures 2
• Proper specimen handling following evidence-based best practices is crucial to minimize preanalytical errors 5

Testing Methodologies

• Next-generation sequencing (NGS) is increasingly utilized for comprehensive genomic profiling 2, 6
• Real-time PCR for highly targeted mutation detection 2
• Sanger sequencing requires ≥25-30% tumor content after enrichment 2
• FISH for copy number alterations and gene rearrangements 2

Important Limitations and Caveats

• Most tumor markers lack sufficient sensitivity and specificity for population-based screening and are primarily used for prognosis, treatment selection, and monitoring 1, 4
• Cell-free DNA testing is most effective when combined with other biomarkers rather than as standalone screening, with sensitivity for early-stage disease being particularly low 5
• A peripheral blood smear alone is insufficient for definitive diagnosis of hematologic malignancy; bone marrow examination remains the gold standard 7
• Tumor biomarker tests should only be used if they have analytical validity (accurate, reproducible, reliable) and demonstrated clinical utility (better outcomes when applied) 8
• The low prevalence of specific cancer types in asymptomatic subjects limits biomarker application for early detection 4