Evaluation of beta1,4-galactosyltransferase as a potential biomarker for the detection of subclinical disease after the completion of primary therapy for ovarian cancer.
OBJECTIVE
Approximately 50% of patients with ovarian cancer who have normal CA 125 levels at the completion of therapy have persistent disease. In an effort to improve the ability to detect small volume disease, we have evaluated the usefulness of N-acetylglucosamine:beta1,4-galactosyltransferase as a potential biomarker for the detection of subclinical disease after the completion of primary therapy for ovarian cancer.


METHODS
The sera of 33 patients with stage IIIC epithelial ovarian cancer in complete clinical remission after chemotherapy (CA 125 <35 units/mL and negative computed tomography scan) who underwent second-look surgery were examined for N-acetylglucosamine:beta1,4-galactosyltransferase activity. The values were determined from sera that had been obtained before primary cytoreductive operation and before second-look surgery after the completion of platinum-based chemotherapy. Determinations of the levels of CA 125 were performed with the Bayer Immuno ITM CA-125 II assay. N-acetylglucosamine:beta1,4-galactosyltransferase activity was determined by measuring the transfer of galactose from uridine diphosphate- carbon 14-labeled galactose to the terminal N-acetylglucosamine residue of a very well-defined synthetic acceptor, N-acetylglucosamine:beta1,6GalNAc(alpha)-o-benzyl, which is a portion of the core structure of mucin glycoproteins. The cutoff value of N-acetylglucosamine:beta1,4-galactosyltransferase was determined to be 22,000 counts/min, based on the analysis of 25 healthy control subjects. Correlation between serum CA 125 and N-acetylglucosamine:beta1,4-galactosyltransferase levels was determined with the use of the Pearson correlation coefficient. The ability of galactosyltransferase to identify small volume disease correctly was also evaluated.


RESULTS
There was a significant correlation between serum CA 125 and N -acetylglucosamine:beta1,4-galactosyltransferase levels before the operation (r = 0.57; P =.03) but not before second-look surgery (r = 0.10; P =.57). Thirteen patients (39.4%) had residual disease at second-look surgery. Elevated N-acetylglucosamine:beta-1,4galactosyltransferase activity >22,000 cpm correctly identified 10 of these patients (76.9%). The sensitivity, specificity, and positive and negative predictive values of N-acetylglucosamine:beta1,4-galactosyltransferase activity (>22,000 counts/min) for the prediction of residual disease at second-look surgery were 77%, 45%, 48%, and 77%, respectively.


CONCLUSIONS
Our comparative study of serum CA 125 and N -acetylglucosamine:beta1,4-galactosyltransferase levels showed a significant correlation between the two tumor markers before the beginning of ovarian cancer therapy. This correlation disappeared before second-look surgery because 60% of patients with normal serum CA 125 and N-acetylglucosamine:beta1,4-galactosyltransferase levels. CA 125 antigen appears to be inferior to N -acetylglucosamine:beta1,4-galactosyltransferase in the detection of small-volume residual disease. N-acetylglucosamine:beta1,4-galactosyltransferase may be useful as a biomarker in the monitoring of patients with ovarian cancer when the serum CA 125 level is normal. These findings require confirmation in larger studies.
Odunsi
Kunle
K
Department of Gynecological Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Ghamande
Sharad
S
Chandrasekaran
E V
EV
Ta
Alyssa
A
Moysich
Kirsten B
KB
Driscoll
Deborah
D
Matta
Khushi
K
Lele
Shashikant
S
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D005260:Female; D006801:Humans; D008875:Middle Aged; D009237:N-Acetyllactosamine Synthase / Q000097:blood*; D018365:Neoplasm, Residual; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000097:blood / Q000628:therapy*
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D009237:N-Acetyllactosamine Synthase