Unit Converter
CYFRA 21-1
(Cytokeratin-19 Fragment – Lung Cancer Tumor Marker)
Synonyms
- CYFRA 21-1
- Cytokeratin-19 fragment
- CK-19 fragment
- Keratin-19 soluble fragment
- Lung cancer cytokeratin marker
Units of Measurement
- ng/mL
- µg/L
- µg/dL
- µg/100 mL
- µg%
1 ng/mL = 1 µg/L
µg/dL = µg/100 mL = µg%
Description
CYFRA 21-1 is a soluble fragment of cytokeratin-19, a structural protein present in epithelial cells. When epithelial tumor cells undergo apoptosis or necrosis, CK-19 fragments are released into the bloodstream.
CYFRA 21-1 is a tumor marker primarily used in lung cancer, especially:
- Non-small cell lung carcinoma (NSCLC)
- Most specific for squamous cell carcinoma subtype
It is also helpful for treatment monitoring, prognosis, and detecting recurrence.
Physiological Role
- CK-19 is part of the cytoskeleton of epithelial cells.
- Not normally shed in large amounts.
- Tumor cell breakdown → elevated CYFRA levels.
Clinical Significance
Elevated CYFRA 21-1
1. Lung Cancer (Most Important Use)
Highly useful in:
- NSCLC (squamous cell type) – highest sensitivity
- Advanced/metastatic disease
- Monitoring therapy response
- Detection of recurrence
Not used as a screening test, but valuable after diagnosis.
2. Other Malignancies
Moderate elevation in:
- Esophageal cancer
- Bladder cancer
- Head & neck cancers
- Cervical cancer
- Breast cancer (rare)
3. Benign Conditions (Mild Elevation)
Can show slight increases in:
- Pneumonia
- Chronic obstructive lung disease
- Pulmonary fibrosis
- Tuberculosis
- Renal insufficiency
These elevations are generally <10 ng/mL.
Low or Normal CYFRA 21-1
Normal values do not exclude lung cancer.
Some tumors (adenocarcinoma) may not shed CK-19 significantly.
Reference Intervals
(Tietz 8E + IASLC + NCCN + Mayo + ARUP)
Normal Range (Adults)
- < 3.3 ng/mL (≈ <3.3 µg/L)**
Ranges vary slightly by kit (some use <3.5 ng/mL).
Diagnostic Interpretation
| CYFRA 21-1 Level | Interpretation |
| < 3.3 ng/mL | Normal |
| 3.3–10 ng/mL | Suspicious; benign lung disease or early cancer |
| > 10 ng/mL | Suggestive of malignancy, especially NSCLC |
| > 20 ng/mL | Highly suggestive of advanced squamous cell carcinoma |
Monitoring
- Falling levels → good treatment response
- Rising levels → recurrence or progression
Unit Meanings
| Unit | Meaning |
| ng/mL | nanogram per milliliter |
| µg/L | microgram per liter |
| µg/dL | microgram per deciliter |
| µg/100 mL = µg% | identical to µg/dL |
Diagnostic Uses
1. Non-Small Cell Lung Carcinoma (NSCLC)
- Best marker for squamous cell carcinoma
- Useful for:
- Baseline assessment
- Monitoring chemotherapy
- Monitoring immunotherapy
- Detecting residual disease
- Detecting recurrence after surgery or radiation
- Baseline assessment
2. Prognostic Marker
Higher CYFRA levels correlate with:
- Higher tumor burden
- Poorer survival
- Advanced staging
3. Use with Other Lung Markers
Often combined with:
- CEA
- NSE
- Pro-GRP
- SCC antigen
The combination improves diagnostic sensitivity.
4. Monitoring Non-malignant Lung Disease
Sometimes used to track severity in:
- ILD
- Pulmonary fibrosis
- Post-infection lung damage
Analytical Notes
- Serum or plasma acceptable
- Avoid hemolysis
- Renal failure may mildly elevate levels
- Immunoassays (ECLIA/CLIA) commonly used
- Serial measurements should use the same platform
Clinical Pearls
- CYFRA 21-1 is more sensitive than CEA for squamous cell carcinoma.
- Not useful for screening the general population.
- Very high levels (>20 ng/mL) almost always indicate advanced NSCLC.
- Post-treatment rising CYFRA levels detect recurrence earlier than imaging in some cases.
- CYFRA is often elevated even when troponins/BNP are normal in patients with lung cancer.
Interesting Fact
CYFRA 21-1 was developed after identifying a specific 21-kDa fragment of cytokeratin-19 released during tumor cell apoptosis - hence the name.
References
- Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Tumor Markers.
- IASLC Lung Cancer Biology Guidelines.
- NCCN Non-Small Cell Lung Cancer Guidelines.
- IFCC Tumor Marker Working Group.
- Mayo Clinic Laboratories - CYFRA 21-1.
- ARUP Consult - Lung Cancer Markers.
- MedlinePlus / NIH - CYFRA 21-1.