Cytokeratin-19 Fragment (CYFRA
21-1) in Bladder Cancer

Morita, Tatsuo; Kikuchi, Takao; Hashimoto, Shinichi; Kobayashi, Yutaka; Tokue, Akihiko

doi:10.1159/000480865

Cited by 30 publications

(9 citation statements)

References 11 publications

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“…In the clinic, these peripheral proteins are usually regarded as tumor makers for non-invasive diagnostic tools to identify cancer, as well as predictor of prognosis and therapeutic effect. Until now, cytokeratin 19 fragment antigen 21–1 (Cyfra21–1), carbohydrate antigen 19–9 (CA19–9), carbohydrate antigen 72–4 (CA72–4), carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC-Ag) have been reported to be commonly used in diagnosis and as prognostic predictors of a variety of cancers [6–11], including ESCC [5, 12, 13]. However, which is the best tumor biomarker for the predicting prognosis in patients with ESCC remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Clinical use of tumor biomarkers in prediction for prognosis and chemotherapeutic effect in esophageal squamous cell carcinoma

et al. 2019

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Background Growing evidence has indicated that tumor biomarkers, including cytokeratin 19 fragment antigen 21–1 (Cyfra21–1), carbohydrate antigen 19–9 (CA19–9), carbohydrate antigen 72–4 (CA72–4), carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC-Ag) were reported to be commonly used in diagnosis and prognosis in esophageal squamous cell carcinoma (ESCC). However, which is the best marker for predicting prognosis remains unknown. Few papers focused on the relationship between tumor biomarkers and postoperative treatment in ESCC. Methods A total of 416 ESCC patients were enrolled in this study. The association between tumor markers and overall survival (OS) was analyzed using Kaplan-Meier method with log-rank test, followed by multivariate Cox regression models. Results The results of Cox multivariate analysis indicated that among these tumor biomarkers, CA19–9 (≥ 37 vs. < 37) [hazard ratio (HR) = 2.130, 95% confidence interval (CI) = 1.138–3.986, p = 0.018] and CEA (≥ 5 vs. < 5) (HR = 1.827, 95% CI = 1.089–3.064, p = 0.022) were the independent prognostic factors of poor OS. For the ESCC patients with CA19–9 < 37, CEA < 5 or SCC-Ag < 1.5, the surgery plus postoperative chemotherapy group had a significantly longer OS than the surgery group alone ( p < 0.05), but this significant difference of OS between these two groups cannot be found in patients with CA19–9 ≥ 37, CEA ≥ 5 or SCC-Ag ≥ 1.5 ( p > 0.05). Conclusions CEA and CA19–9 maybe are superior to other tumor biomarkers as prognostic indicators in ESCC. CA19–9, CEA, SCC-Ag may be useful in predicting the therapeutic effect of postoperative chemotherapy in ESCC. Electronic supplementary material The online version of this article (10.1186/s12885-019-5755-5) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Clinical use of tumor biomarkers in prediction for prognosis and chemotherapeutic effect in esophageal squamous cell carcinoma

et al. 2019

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“…The epitopes for these antibodies are located in the rod domain of the polypeptide chain within amino acids 311–367 12, 13. The elevation of cytokeratin 19 levels in the serum has been shown mainly in patients with metastatic bladder carcinoma; therefore, it cannot be used as a serum marker for early detection 14, 15…”

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confidence: 99%

Evaluation of urine CYFRA 21‐1 for the detection of primary and recurrent bladder carcinoma

Nisman

Barak

Shapiro

et al. 2002

Cancer

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BACKGROUND The urinary concentration of soluble cytokeratin 19 fragments, measured by the CYFRA 21‐1 assay, may be used for the noninvasive, early detection of bladder carcinoma. METHODS This prospective study examined urine samples from 325 patients. The authors included 152 patients who presented with hematuria or irritative voiding symptoms (Group 1), 107 patients who were under surveillance after undergoing transurethral resection of bladder carcinoma (Group 2), 46 patients with urinary tract pathology other than bladder carcinoma (Group 3), and 20 healthy participants (Group 4). The urine concentration of CYFRA 21‐1 was measured by an immunoradiometric assay. The patients in Groups 1 and 2 underwent cytoscopy and urine cytopathology. Biopsies were obtained if a tumor was seen on cytoscopy or if there was a suspicion of carcinoma in situ (CIS). RESULTS The optimal cut‐off concentration for the detection of primary bladder tumors, 4.9 μg/L, resulted in a sensitivity of 79.3% and a specificity of 88.6%. The optimal threshold for the detection of recurrent bladder tumors (excluding patients who had been treated with intravesical bacillus Calmette–Guerin [BCG]), 4.04 μg/L, resulted in a sensitivity of 76.2% and a specificity of 84.2%. There was no significant advantage for centrifugation of the urine samples or for determination of the creatinine concentration in the urine samples. The CYFRA 21‐1 assay of urine samples provided a three‐fold greater sensitivity compared with the sensitivity of cytology for detecting Grade 1 transitional cell tumors. CYFRA 21‐1 detected 91.9% of Grade 3 tumors, 100% of CIS, and 92.8% of invasive bladder tumors (T2 or higher classification). The CYFRA 21‐1 assay detected all tumors that had positive cytology with the exception of only one tumor. Conversely, the assay identified 71% of primary tumors and 65% of recurrent tumors that were missed by cytopathology. Urinary stones, infection, and previous intravesical BCG immunotherapy caused many false positive results. CONCLUSIONS The urinary CYFRA 21‐1 assay is a useful test for the noninvasive detection of bladder carcinoma and for surveillance of patients who were not treated previously with BCG. It may be used in combination with urine cytology and bladder ultrasound. Multi‐institutional trials are required to compare the accuracy as well as the cost of this combination of tests with cystoscopy. Cancer 2002;94:2914–22. © 2002 American Cancer Society. DOI 10.1002/cncr.10565

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“…11 In contrast, for serum CYFRA 21-1 measurements using the CLEIA method, the reported upper limit of the percentiles for healthy individuals is 1.6 ng/mL, 12 which is lower than that set for measurements using the EIA method. Therefore, for our study, we set the cutoff value for CYFRA 21-1 at 2.2 ng/mL based on the mean value for healthy subjects + 3 standard deviation (SD) according to the protocol used to set the cutoff value in previous studies, 13,14 which was lower than that set for measurements using the EIA method. The cutoff value for serum CEA was set at 5.0 ng/mL, which is the upper limit of normal.…”

Section: Methodsmentioning

confidence: 99%

CYFRA 21-1 predicts the efficacy of nivolumab in patients with advanced lung adenocarcinoma

et al. 2018

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CYFRA 21-1 is a prognostic marker for non-small cell lung cancer. The serum CYFRA 21-1 level is also known as an adjunct for the diagnosis of lung squamous cell carcinoma. This study aimed to examine whether CYFRA 21-1 has predictive implications for nivolumab therapy in patients with advanced lung adenocarcinoma. Of the 79 patients who were treated with nivolumab therapy at the Shizuoka Cancer Center between December 2015 and September 2016, we retrospectively reviewed the data of 50 patients. The patient characteristics were as follows: age <70/≥70 years: 43 (86%)/7; male/female: 31 (62.0%)/19; Eastern Cooperative Oncology Group performance status 0-1/2: 43 (86%)/7; smoking status: no/yes: 18 (36%)/32; epidermal growth factor receptor mutation status negative/positive: 36 (72%)/14; CYFRA 21-1 ≥2.2/<2.2 ng/mL: 28 (56%)/22; carcinoembryonic antigen ≥5/<5 ng/mL: 29 (58%)/21; and number of prior regimens 2-3/≥4: 16 (32%)/34. With a median follow-up of 263.5 (range, 64-352) days, the median progression-free survival was 70 days. The clinical variables investigated using univariate analysis were as follows: age (p = 0.423), carcinoembryonic antigen (p = 0.888), epidermal growth factor receptor mutation status (p = 0.105), performance status (p = 0.968), sex (p = 0.210), number of prior regimens (p = 0.146), CYFRA 21-1 (p = 0.026), and smoking status (p = 0.041). A multivariate analysis identified a serum CYFRA 21-1 level ≥2.2 ng/mL as an independent predictor of a favorable outcome (hazard ratio, 0.44; 95% confidence interval, 0.23-0.85; p = 0.015; median progression-free survival, 155 vs 51.5 days). In conclusion, CYFRA 21-1 might be an independent predictor of outcome for patients with advanced lung adenocarcinoma treated with nivolumab.

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Cytokeratin-19 Fragment (CYFRA 21-1) in Bladder Cancer

Cited by 30 publications

References 11 publications

Clinical use of tumor biomarkers in prediction for prognosis and chemotherapeutic effect in esophageal squamous cell carcinoma

Clinical use of tumor biomarkers in prediction for prognosis and chemotherapeutic effect in esophageal squamous cell carcinoma

Evaluation of urine CYFRA 21‐1 for the detection of primary and recurrent bladder carcinoma

CYFRA 21-1 predicts the efficacy of nivolumab in patients with advanced lung adenocarcinoma

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