Cell-free 59 kDa immunoreactive integrin-linked kinase: a novel marker for ovarian carcinoma.
OBJECTIVE
We reported that the expression of integrin-linked kinase (ILK) is up-regulated in ovarian carcinomas and that ovarian cancer cells have high expression of ILK. In this study, we have examined the expression of cell-free 59 kDa immunoreactive (ir)ILK in the serum and peritoneal fluid (PTF) of patients with ovarian cancer and evaluated its potential as a serum biomarker for early-stage screening and for monitoring clinical status of patients after chemotherapy treatment.


METHODS
Thirty-six serum specimens, including normal (n = 6), benign (n = 6), borderline (n = 4), grade 1 (n = 5), grade 2 (n = 5), and grade 3 (n = 10), were evaluated for the expression of irILK by Western blotting. The expression of irILK was evaluated in PTF (n = 10) and peritoneal washings from women with benign ovarian cysts (n = 4). In addition, tissue-conditioned medium obtained from the cultures of primary ovarian tumors (n = 9) was examined for the presence of irILK. Finally, the potential of serum irILK as a biomarker for ovarian cancer screening was evaluated by comparison with cancer antigen 125 (CA 125) concentrations in cancer patients before and after chemotherapy.


RESULTS
irILK expression was present in normal serum and in serum of patients with benign ovarian tumors. irILK expression was 6-9-fold higher in the serum of patients with grade 1, grade 2, and grade 3 ovarian cancer than in the serum of healthy volunteers and patients with benign ovarian tumors (P < 0.01). Enhanced expression of irILK in the serum of ovarian cancer patients correlated with the concentration of CA 125. High expression of irILK was present in all 10 PTF tested. Tissue-conditioned medium prepared from malignant ovarian tumors had 4-fold more irILK expression than conditioned medium obtained from borderline and benign tumors (P < 0.01). irILK expression in serum of cancer patients was reduced to basal normal levels after six cycles of Taxol/carboplatin and was consistent with the change of CA 125 levels before and after chemotherapy.


CONCLUSIONS
These data suggest that irILK is an ovarian tumor-associated antigen and implicates its potential not only as a biomarker for early-stage screening but also as a marker for monitoring the clinical condition of patients after treatment.
Ahmed
Nuzhat
N
Gynaecological Cancer Research Centre, Royal Women's Hospital and The Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia. nuzhata@unimelb.edu.au
Oliva
Karen
K
Rice
Greg E
GE
Quinn
Michael A
MA
D014408:Biomarkers, Tumor; D015153:Blotting, Western; D018394:CA-125 Antigen / Q000096:biosynthesis; D002277:Carcinoma / Q000097:blood / Q000378:metabolism*; D002474:Cell-Free System; D017077:Culture Media, Conditioned; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000097:blood / Q000378:metabolism*; D010537:Peritoneum / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D013997:Time Factors; D015854:Up-Regulation; D000099200:Scaffold Protein ILK
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D017077:Culture Media, Conditioned; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK