CYFRA 21-1

CYFRA 21-1 is a blood tumour marker. It measures a fragment of cytokeratin 19, an epithelial cell protein, and is used mainly in non-small-cell lung cancer: to assess disease before treatment, monitor treatment effect and identify recurrence earlier. It is not a test to detect cancer in healthy people.

Who the test is for

• people with non-small-cell lung cancer before treatment, as a baseline: if raised then, it is useful for subsequent monitoring;
• people treated for non-small-cell lung cancer, because a fall usually accompanies a good treatment response;
• people attending follow-up after treatment, because a new rise may warn of recurrence;
• sometimes people undergoing investigation of a suspicious lung abnormality, as additional information alongside imaging and biopsy, when a doctor considers it appropriate.

What CYFRA 21-1 is and what it shows

Cytokeratins are structural proteins providing strength to epithelial cells lining the airways, digestive and urinary tracts and skin. When these cells break down, cytokeratin 19 fragments enter blood, where they can be measured as CYFRA 21-1.

The highest values are usually found in non-small-cell lung cancer, particularly squamous cell carcinoma. CYFRA 21-1 can also be raised in other tumours, such as head and neck, oesophageal, bladder or cervical tumours, and in benign diseases. The marker therefore does not show whether someone has cancer, where a tumour is or its type. Tumour type is determined by histopathological examination of biopsy tissue.

CYFRA 21-1 is not a screening test: it can be raised without cancer and normal with a tumour, particularly early on. Croatia has a national low-dose CT lung cancer early detection programme for long-term smokers. Programme eligibility and early signs are described in Early symptoms of lung cancer.

Types of lung cancer

According to cell appearance under a microscope, lung cancer is divided into two main groups because treatments differ:

• non-small-cell lung cancer, around 85 % of cases; this includes adenocarcinoma, squamous cell carcinoma and large-cell carcinoma;
• small-cell lung cancer, around 15 % of cases, usually growing faster.

CYFRA 21-1 is used primarily in non-small-cell cancer. In small-cell cancer, NSE, is more often monitored, while in adenocarcinoma a doctor sometimes also requests CEA.

Preparation and sample

CYFRA 21-1 is measured in venous blood and fasting is unnecessary. For long-term monitoring it is best measured in the same laboratory because different methods cannot be compared directly.

How to interpret the result

The reference interval depends on method and is printed on the report. Results are interpreted alongside imaging and previous marker values.

Raised CYFRA 21-1

A raised value alone does not mean cancer. CYFRA 21-1 can also rise with:

• reduced kidney function, because the marker is removed from blood more slowly;
• liver disease;
• some benign lung diseases, such as inflammation.

In people treated for lung cancer, the trend over several measurements matters more than one value. A sustained rise can warn of progression or recurrence, checked using imaging.

Normal CYFRA 21-1

A normal result does not rule out lung cancer. In some patients the marker stays within the reference interval, so a normal result is no reason to ignore symptoms such as a persistent cough, coughing blood or unexplained weight loss.

How to arrange testing

You can have blood taken without an appointment or referral at one of our branches across Croatia (listed under Contact). Prices for all tests and panels are available in the service price list.

Frequently asked questions

What does raised CYFRA 21-1 mean?

It may suggest cancer, most often lung cancer, but also rises with reduced kidney function, liver disease and some benign lung conditions. Results are assessed alongside symptoms, examination and imaging, and testing is repeated if needed.

Can CYFRA 21-1 be used for early lung cancer detection?

No. In healthy asymptomatic people, results more often confuse than help. Low-dose CT within the national programme, accessed through a GP, is used for early detection in smokers.

What is the difference between CYFRA 21-1, NSE and CEA?

All are used in lung cancer but for different types: CYFRA 21-1 mainly in non-small-cell cancer, NSE in small-cell cancer and CEA in adenocarcinoma and some other tumours. A doctor decides which marker is appropriate based on biopsy findings.

What is a normal CYFRA 21-1 value?

There is no single threshold for all laboratories because it depends on method. The limit applying to your result is printed alongside it. We explain other markers and when they are useful in the article Tumour markers.