CYFRA 21-1 (Cytokeratin 19 Fragment)

Optimal Result: 0 - 2.08 ug/L.

The CYFRA 21-1 is well known as tumor maker of lung cancer and is not influenced by environmental factors.

CYFRA 21-1 can be considered as the biomarker of choice for non-small cell lung cancer (primarily for squamous cell and large cell carcinoma subtypes).

In adenocarcinoma of the lung (a type of non-small cell lung cancer), a combination of CYFRA 21-1 and Carcinoembryonic antigen (CEA) has been found to be the most useful.

The main indication for CYFRA 21-1 is monitoring the course of NSCLC.

Successful therapy is accompanied by a rapid decrease of serum levels to the normal range Increased CYFRA 21-1 levels have also been described in non-malignant diseases (i.e. pneumonia, sepsis) and renal dysfunction.

Therefore evaluation of renal function (i.e. by measuring serum creatinine levels) should be considered in cases of high CYFRA 21-1 levels that are not consistent with the diagnostic and clinical characteristics of the patient.

What are cytokeratins?

Cytokeratins are structural proteins forming the subunits of epithelial intermediary filaments. Twenty different cytokeratins have so far been identified, CYFRA 21-1 which is a fragment of cytokeratin 19, being the most prominent one. Intact cytokeratin polypeptides are poorly soluble, but soluble fragments like CYFRA 21-1, are frequently released into the blood of cancer patients and can be detected in serum. Although being expressed in different organs, its major occurrence is in the lung.

What is NSCLC?

Approximately 85% of all lung cancers are classified as non-small-cell lung cancer (NSCLC), including squamous cell carcinoma (SCC), lung adenocarcinoma (LAD), and large cell carcinoma (LCC), and 10% are small cell lung cancer and 5% other histological variants with distinct biological behavior and genetic alterations.

The NSCLC is potentially curable by surgical resection if it is discovered at an early stage. However, patients with resected NSCLC are at risk for recurrence of disease, since there are no effective tools to predict which patients are at highest risk. Early detection and diagnosis is urgent for the sake of an effective treatment strategy for lung cancer.

- Non-small cell lung cancer is a disease in which malignant (cancer) cells form in the tissues of the lung.

- There are several types of non-small cell lung cancer.

- Smoking is the major risk factor for non-small cell lung cancer.

- Signs of non-small cell lung cancer include a cough that doesn't go away and shortness of breath.

- Tests that examine the lungs are used to diagnose and stage non-small cell lung cancer.

- If lung cancer is suspected, a biopsy is done.

- Certain factors affect prognosis (chance of recovery) and treatment options.

- For most patients with non-small cell lung cancer, current treatments do not cure the cancer.

In Addition, studies have shown that CYFRA 21-1 might also be a good marker for HNC (= Head and Neck cancers)

Links:

https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/1097-0142%2820000915%2989%3A6%3C1285%3A%3AAID-CNCR13%3E3.0.CO%3B2-G

https://www.cancer.gov/types/lung/patient/non-small-cell-lung-treatment-pdq

https://www.cancer.gov/types/head-and-neck/head-neck-fact-sheet

https://doi.org/10.1177/1724600819868234

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6508679/

References:

Wieskopf B, Demangeat C, Purohit A, Stenger R, Gries P, Kreisman H, Quoix E. Cyfra 21-1 as a biologic marker of non-small cell lung cancer. Evaluation of sensitivity, specificity, and prognostic role. Chest. 1995 Jul;108(1):163-9. doi: 10.1378/chest.108.1.163. PMID: 7541742.

Rastel D, Ramaioli A, Cornillie F, Thirion B. CYFRA 21-1, a sensitive and specific new tumour marker for squamous cell lung cancer. Report of the first European multicentre evaluation. CYFRA 21-1 Multicentre Study Group. Eur J Cancer. 1994;30A(5):601-6. doi: 10.1016/0959-8049(94)90528-2. PMID: 7521651.

Lai RS, Hsu HK, Lu JY, Ger LP, Lai NS. CYFRA 21-1 enzyme-linked immunosorbent assay. Evaluation as a tumor marker in non-small cell lung cancer. Chest. 1996 Apr;109(4):995-1000. doi: 10.1378/chest.109.4.995. PMID: 8635383.

Pujol JL, Grenier J, Daures JP, Daver A, Pujol H, Michel FB. Serum fragment of cytokeratin subunit 19 measured by CYFRA 21-1 immunoradiometric assay as a marker of lung cancer. Cancer Res. 1993 Jan 1;53(1):61-6. PMID: 7677981.

Liu L, Xie W, Xue P, Wei Z, Liang X, Chen N. Diagnostic accuracy and prognostic applications of CYFRA 21-1 in head and neck cancer: A systematic review and meta-analysis. PLoS One. 2019 May 9;14(5):e0216561. doi: 10.1371/journal.pone.0216561. PMID: 31071161; PMCID: PMC6508679.

What does it mean if your CYFRA 21-1 (Cytokeratin 19 Fragment) result is too high?

Elevations of cytokeratins are observed in lung cancer of all histologic types of non-small-cell lung cancer (NSCLC).

- CYFRA 21-1 should not be used as a diagnostic tool for the detection and diagnosis of lung cancer.
- Results should not be interpreted as evidence of presence or absence of malignancy.
- Interpretation of result must always be in correlation with clinical and diagnostic findings and under the supervision of the patient's attending physician.

Elevated pre-treatment levels may be associated with unfavorable prognosis, and decreasing levels during therapy predict an objective response to treatment. However, the level of CYFRA 21-1 cannot be used as absolute evidence for the presence or absence of disease and results must be viewed in context with other clinical evidence.

CYFRA 21-1 may also be elevated in:

- Benign respiratory disease

- Other cancers:

  • Urologic
  • Gastrointestinal
  • Gynecological
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