Annals of Oncology Advance Access published online on August 22, 2008
Annals of Oncology, doi:10.1093/annonc/mdn552
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Serum YKL-40 as a marker for cervical adenocarcinoma
1 Department of Reproductive Medicine
2 Department of Molecular Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan
* Correspondence to: Dr. A. Mitsuhashi, Department of Reproductive Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. Tel: +81-43-226-2362; Fax: +81-43-226-2342; E-mail: antira{at}faculty.chiba-u.jp
Background: The current study examined the clinical usefulness of YKL-40 in detection and prognosis of uterine cervical cancer.
Patients and methods: Serum levels of YKL-40, cancer antigen 125 (CA 125), carbohydrate antigen 19-9 (CA19-9), and squamous cell carcinoma (SCC) antigen were determined by enzyme-linked immunosorbent assay in women with benign gynecologic disease (n = 24), cervical malignancy (SCC, n = 104; adenocarcinoma, n = 37), and age-matched healthy controls (n = 45). Immunohistochemical analysis for local YKL-40 expression was carried out on 28 adenocarcinomas.
Results: Receiver operating characteristic curve analysis showed that YKL-40 [area under the curve (AUC) = 0.882] was significantly better at discriminating adenocarcinoma from healthy control than SCC antigen, CA 125, and CA19-9. For SCC, YKL-40 (AUC = 0.898) carried out similarly to SCC antigen and was better than CA 125 and CA19-9. Using a cut-off YKL-40 value of 92.2 ng/ml, sensitivity of YKL-40 in stage I adenocarcinoma (68%) was higher than that of the other three markers (11%–21%). Tumor-associated macrophages showed immunoreactivity for YKL-40 in 2 of 28 adenocarcinoma tissue samples, but adenocarcinoma cells themselves were nonimmunoreactive in all samples. Multivariate Cox regression analysis revealed that elevated pretreatment YKL-40 levels predicted unfavorable prognosis, independent of International Federation of Gynecology and Obstetrics stage and age at diagnosis.
Conclusions: Pretreatment serum YKL-40 level is a possible prognosticator of cervical adenocarcinoma.
adenocarcinoma, cervical, tumor marker, YKL-40
Received for publication October 12, 2007. Revision received June 19, 2008. Accepted for publication July 10, 2008.