Preoperative serum YKL-40 is a marker for detection and prognosis of endometrial cancer.
OBJECTIVE
YKL-40 is a secreted glycoprotein of the chitinase family that has been previously described as a diagnostic and prognostic marker for a number of cancers, including epithelial ovarian cancer. In this study, we examined the frequency of serum elevation as well as the diagnostic and prognostic significance of this serum marker in endometrial cancer.


METHODS
Preoperative serum levels of YKL-40 and CA125 were evaluated by enzyme-linked immunosorbent assay (ELISA) for all endometrial cancer patient samples (34) available in the Memorial Sloan-Kettering Cancer Center Gynecology Service Tissue Bank between the years 1987 and 2002, and compared to a cohort of normal individuals. A YKL-40 value of 61 ng/mL has previously been determined to represent the upper limit of normal. YKL-40 values were correlated with clinical characteristics, including patient age, tumor grade, histology, clinical stage, and clinical outcome (progression-free survival [PFS] and overall survival [OS]).


RESULTS
YKL-40 was elevated (>61 ng/mL) in 26 (76%) of 34 endometrial cancer patients compared with elevations of CA125 in 21 (62%) of 34 patients (P=0.09). Twenty-eight (82%) of all 34 patients had elevations of either CA125 or YKL-40 or both; 16 (89%) of 18 advanced-stage endometrial cancer patients had elevation of at least one of these two markers. Median preoperative YKL-40 value was 137 ng/mL (range, 22-1738 ng/mL) for endometrial cancer patients compared with 28 ng/mL (range, 15-72 ng/mL) for normal healthy subjects (P<0.0001). There was no statistically significant association of YKL-40 with patient age, tumor grade, histology, or stage. Elevation of YKL-40 (>80 ng/mL) was correlated with poor clinical outcome in univariate analysis, but was not demonstrated in multivariate analysis. At 5 years' follow-up, the PFS rate was 80% for patients with YKL-40<80 ng/mL compared with 43% for patients with YKL-40>80 ng/mL (P=0.004). The 5-year OS rate for patients with YKL-40<80 ng/mL was 79% compared with 48% for patients with YKL-40>80 ng/mL (P=0.047).


CONCLUSIONS
Preoperative serum YKL-40 is frequently elevated and may represent a novel marker for the detection of endometrial cancer and the identification of high-risk subsets of patients with worse clinical outcome. Further investigation of this promising endometrial cancer marker in larger studies is warranted.
Diefenbach
Catherine S M
CS
Gynecologic Medical Oncology, Department of Medicine, Howard 903, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Shah
Zharna
Z
Iasonos
Alexia
A
Barakat
Richard R
RR
Levine
Douglas A
DA
Aghajanian
Carol
C
Sabbatini
Paul
P
Hensley
Martee L
ML
Konner
Jason
J
Tew
William
W
Spriggs
David
D
Fleisher
Martin
M
Thaler
Howard
H
Dupont
Jakob
J
D054392:Adipokines; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D000071451:Chitinase-3-Like Protein 1; D016889:Endometrial Neoplasms / Q000097:blood* / Q000473:pathology / Q000601:surgery; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D037102:Lectins; D008875:Middle Aged; D009367:Neoplasm Staging; D011300:Preoperative Care; D012372:ROC Curve; D016896:Treatment Outcome
D054392:Adipokines; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins