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Title: The Role of Cytokeratin-19 in Diagnosis of Cancer Bladder
Authors: Azza S. Hassanien; Mona M Nossier; Nariman M Zahran; Marwa S Wahdan; Tarek Swellam ; Dalal A. Aboul-Magd.
DOI:
Aff: Haematology, Departments, Theodor Bilharz Research Institute, Giza, Egypt.
Author Email:
Keywords: primary bladder carcinoma; BPH; immunoassay; immunohistochemistry; Cytokeratin-19 (Cyfra21-1); urine cytology; FDPs
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Abstract:Background: Detection of urinary bladder cancer using diagnostic markers is still presenting
a challenge. Objective: Aiming to give an insight into the diagnostic performance and reliability of both
soluble and tissue cytokeratin 19 (Cyfra 21-1) in primary bladder carcinoma. Patients and Methods: The
study was conducted on 45 subjects, including 30 cases (Group I) of histopathologically-proven primary
bladder carcinoma (18 TCC, 12 SqCC), 8 patients (Group II) of benign prostatic hyperplasia (BPH), and
control group (Group III) of 7 healthy volunteers. Serum and voided urine samples, from all studied
groups, were subjected to Cyfra 21-1 immunoassay. Immunohistochemistry was performed on tissue
biopsies collected from patients in group I and II. Urinary Cyfra 21-1 was evaluated in relation to urine
cytology and urinary fibrin/fibrinogen degradation products (FDPs) assay. Results: The optimal cut-off
concentration of serum Cyfra 21-1 for the detection of primary bladder tumor, 2.8 ng/ml, resulted in a
sensitivity of 33% and 100% specificity. While for urinary Cyfra 21-1, the best receiver operating
characteristics (ROC) curve analysis revealed a sensitivity of 92% and 100% specificity, at a threshold
value of 5.8 ng/ml. Statistically significant increase was noted, between the mean serum and urine Cyfra
21-1 levels in Group I, compared to other groups. A progressive increase in serum Cyfra 21-1 with
grading and staging was noticed. In addition, urine Cyfra 21-1 provided greater sensitivity compared to
urine cytology and FDPs in diagnosing primary cases. However, immunohistochemical expression of CK
19 revealed a strong positivity in BPH compared to other groups. Among bladder cancer patients, no
correlation was found between serum or urine Cyfra 21-1 levels and its immunohistochemical expression.
In addition, no statistical significant difference could be detected in tissue staining regarding grading and
staging. Conclusions: Urinary Cyfra 21-1 appeared to be superior to both urine cytology and FDPs for
screening primary cases. While, serum Cyfra 21-1 does not show enough sensitivity to justify its
application routinely but increased level with tumor grading or staging may be useful for monitoring the
clinical course. Meanwhile, its immunohistochemical expression, besides being an invasive maneuver, had
relatively lower reliability as a useful detection marker.