Cytokeratin Fragment 21-1 in Gynecologic Malignancy: Comparison with Cancer Antigen 125 and Squamous Cell Carcinoma-Related Antigen

Abstract

We measured serum cytokeratin fragment 21–1 (CYFRA 21–1) levels by a solid-phase immunoradiometric assay in 102 healthy Japanese women, and set the reference value at 1.9 ng/ ml (mean +2 SD of the serum levels based on a linear distribution). Pretreatment serum CYFRA 21–1 levels were also analyzed in 235 women with benign (n = 94) or malignant (n = 141) gynecologic disease, and were compared with the serum levels of CA 125 and SCC. The respective positivity rates for CYFRA 21–1 and CA 125 were 64.0 and 77.2% in ovarian malignancy, while they were 4.2 and 30.8% in benign ovarian masses. CYFRA 21–1 had an accuracy of 61.3% in diagnosing ovarian malignancy, which was higher than that of CA 125 (53.4%). The positive predictive value of CYFRA 21–1 for ovarian malignancy reached 94.1%, which was significantly (p < 0.005) higher than that of CA 125 (68.8%). These findings indicate the potential usefulness of CYFRA 21–1 as a tumor marker for ovarian malignancy. In addition, the positivity rates fo CYFRA 21–1 in cervical cancer (51.2%) and endome-trial cancer (52.2%) were also similar to the respective rates for SCC and CA 125, which suggests that CYFRA 21–1 seems to be a general tumor marker for gynecologic malignancy.

The clinical relevance of serum CYFRA 21-1 assay in patients with ovarian cancer

“…Mobus et al (27) found that ovarian cancer cell lines express large amounts of cytokeratin 19, suggesting that overexpression of cytokeratin 19 paralleled ovarian carcinogenesis. Few data are currently available in the literature about the clinical relevance of serum CYFRA 21-1 assay in the management of patients with ovarian cancer (12,13,22) . By assessing pretreatment serum tumor marker levels in 235 women with different gynecologic diseases, Inaba et al (13) observed that positivity rates for CYFRA 21-1 (cut-off = 1.9 ng/ml) were 64.0% in ovarian malignancy compared with 4.2% in benign ovarian masses.…”

“…Different cytokeratins have been found in human epithelia and have been divided into two subfamilies: basic (cytokeratins [1][2][3][4][5][6][7][8] and acidic (cytokeratins [9][10][11][12][13][14][15][16][17][18][19][20], which can be distinguished on the basis of immunological, peptide mapping, mRNA hybridization, and primary amino acid sequence data (3,4) . Cytokeratin fragments exist also in soluble form and can be detected in the serum with the aid of monoclonal antibodies (5) .…”

“…Cytokeratin fragments exist also in soluble form and can be detected in the serum with the aid of monoclonal antibodies (5) . Soluble cytokeratin fragments have been investigated as tumor markers in several malignancies, including gynecologic cancer (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) . The biochemical pathway by which these fragments are formed in malignant tissues and released into the bloodstream is still uncertain (20) .…”

“…The aim of the present investigation was to assess the clinical relevance of serum CYFRA 21-1 assay in patients with ovarian cancer, given that few data are currently available on this subject in the literature (12,13,22) . The study was conducted retrospectively from a bank of serum samples collected for tumor marker assay.…”

Urine and serum concentrations of Cytokeratin 19 in preeclampsia

“…When present in peripheral blood, cytokeratins are mainly detected as partially degraded, single protein fragments or complexes. A fragment of CK19, Cytokeratin fragment 21-1 (CYFRA 21-1), has been extensively studied in patients with non-small cell lung, esophageal cancer and gynecological malignancy where it has been shown to be a clinically useful prognostic and monitoring marker [16][17][18].…”