title: A combination of serum tumor markers identifies high-risk patients with early-stage squamous cervical cancer.
abstract: We aimed to investigate whether pretreatment serum levels of squamous cell carcinoma (SCC) antigen (SCC-Ag), cytokeratin 19 (CYFRA 21-1) and two mucins (CA 15-3 and CA 125) identify patients with occult disease in early-stage SCC of the cervix. Therefore, pretreatment serum samples were obtained from 78 patients with SCC of the cervix (52 IB, 9 IIA and 18 IIB), and tumor markers were measured with commercial immunoassays. SCC-Ag, CYFRA 21-1 and CA 15-3 (analyzed as continuous variables) were significantly associated with overall (OS) and disease-free survival (DFS) in univariate analysis (p < 0.001 in all cases). Multivariate analysis identified lymph node status as the strongest predictor for OS and DFS (p < 0.001 and p = 0.001, respectively), followed by CYFRA 21-1 (p = 0.060 and p = 0.027, respectively) and CA 15-3 (p = 0.082 and p = 0.017, respectively). Clinical cutoff values for each marker were defined by maximizing the log-rank statistics for OS in the total population: 1.1 microg/l for SCC-Ag (n = 47, 60.3%), 1.4 microg/l for CYFRA 21-1 (n = 47, 60.3%), 40 U/ml for CA 15-3 (n = 11, 14.1%) and 30 U/ml for CA 125 (n = 10, 12.8%). Stage IB patients with positive SCC-Ag and CYFRA 21-1 had significantly lower OS (mean 8.3 years, 95% confidence interval, CI, 5.8-10.7 years) and DFS (mean 7.3 years, 95% CI 4.6-10 years) than all other stage IB patients (OS, mean 14.5 years, 95% CI 13.5-15.5 years; DFS, mean 13.9 years, 95% CI 12.5-15.4 years). Stage IB patients with tumors <4 cm or with negative lymph nodes and positive SCC-Ag and CYFRA 21-1 had significantly poorer OS and DFS compared to all other patients in the same group. Elevated levels of both CA 125 and CA 15-3 (3 patients) were associated with an extremely poor prognosis. In conclusion, a combination of SCC-Ag and CYFRA 21-1 may help to identify early-stage cervical cancer patients with occult disease requiring adjuvant therapy.
authors.affiliation: Department of Obstetrics and Gynecology, Free University Medical Center, Amsterdam, The Netherlands.
authors.forename: Elvira M
authors.initials: EM
authors.lastname: Davelaar
authors.forename: Jonas
authors.initials: J
authors.lastname: van de Lande
authors.forename: Silvia
authors.initials: S
authors.lastname: von Mensdorff-Pouilly
authors.forename: Marinus A
authors.initials: MA
authors.lastname: Blankenstein
authors.forename: René H M
authors.initials: RH
authors.lastname: Verheijen
authors.forename: Peter
authors.initials: P
authors.lastname: Kenemans
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000473:pathology; D005260:Female; D006801:Humans; D053539:Keratin-19 / Q000097:blood; D007633:Keratins / Q000097:blood; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood; D009367:Neoplasm Staging; D011379:Prognosis; D012306:Risk; D015843:Serpins / Q000097:blood; D002583:Uterine Cervical Neoplasms / Q000097:blood* / Q000473:pathology
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D053539:Keratin-19; D018396:Mucin-1; D015843:Serpins; C102012:antigen CYFRA21.1; C051072:squamous cell carcinoma-related antigen; D007633:Keratins