Kallikreins as markers of disseminated tumour cells in ovarian cancer-- a pilot study.
BACKGROUND
Kallikreins are a family of secreted serine proteases, encoded by 15 genes which all localize in tandem on chromosome 19q13.4. Several members of this family have been previously associated with ovarian cancer. Kallikreins 6 (KLK6) and 10 (KLK10) are elevated in tumour cells, serum and ascites fluid of ovarian cancer patients and correlate with disease prognosis. Other kallikreins that have been related to ovarian cancer include KLK4, 5, 7, 8, 9, 11, 13, 14 and 15. We hypothesized that KLK6 and KLK10 can be utilized to monitor dissemination of ovarian cancer cells in blood and ascites fluid of ovarian cancer patients.


METHODS
RNA was isolated by immunomagnetic separation of cancer cells and was amplified by RT-PCR.


RESULTS
Screening for disseminated cancer cells in blood from 24 ovarian cancer patients, with RT-PCR for KLK6 mRNA, resulted in 75% positivity; however, this was not different from the positivity of normal controls. By utilizing KLK10 as a marker, the positivity of patients was 40% versus 20% of controls. Screening of ascites fluid of ovarian cancer patients revealed 90% positivity for KLK6 and KLK10 mRNA compared with 33% for other cancer types. Significant correlations were identified among mRNA of KLK4, 5, 6, 7, 8, 9, 10, 11, 13, 14 and 15 in cancer cells isolated from ascites fluid.


CONCLUSIONS
Kallikrein expression by ovarian cancer cells is not specific enough for detecting disseminated disease. Kallikrein expression may have some value for differentiating ovarian cancer from other types of cancer or from non-malignant diseases that lead to ascites accumulation.
Oikonomopoulou
Katerina
K
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
Scorilas
Andreas
A
Michael
Iacovos P
IP
Grass
Linda
L
Soosaipillai
Antoninus
A
Rosen
Barry
B
Murphy
Joan
J
Diamandis
Eleftherios P
EP
D000230:Adenocarcinoma / Q000097:blood* / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D001201:Ascites / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018189:Immunomagnetic Separation; D007610:Kallikreins / Q000097:blood* / Q000235:genetics / Q000502:physiology; D008297:Male; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D010865:Pilot Projects; D011471:Prostatic Neoplasms / Q000473:pathology; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D012334:RNA, Neoplasm; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C100936:KLK10 protein, human; C103551:KLK6 protein, human; D007610:Kallikreins