Potential markers that complement expression of CA125 in epithelial ovarian cancer.
BACKGROUND
When ovarian carcinoma is diagnosed in stage I, up to 90% of patients can be cured with surgery and currently available chemotherapy. At present, less than 25% of cases are diagnosed at this stage. To increase the fraction of ovarian cancers detected at an early stage, screening strategies have been devised that utilize a rising serum CA125 level to trigger the performance of transvaginal sonography. One limitation of CA125 as an initial step in such a screening strategy is that up to 20% of ovarian cancers lack expression of the antigen. Serum tumor markers that can be detected in ovarian cancers that lack CA125 expression might improve the sensitivity for early detection.


METHODS
From 296 ovarian cancers, 65 (22%) were found to have weak or absent CA125 expression on immunoperoxidase staining. Tissue expression of CA125 was compared to serum CA125 levels. Using immunoperoxidase staining of tissue arrays, we have assessed expression of 10 potential serum tumor markers in the 65 epithelial ovarian cancers with little or no CA125 expression and in ovarian cystadenomas, tumors of low malignant potential, normal ovaries, and 16 other normal tissues.


RESULTS
Low or absent expression of CA125 in surgical specimens of epithelial ovarian cancer was associated with low levels of serum CA125 in pre-operative serum specimens. In ovarian cancers that lacked CA125, all specimens (100%) expressed human kallikrein 10 (HK10), human kallikrein 6 (HK6), osteopontin (OPN), and claudin 3. A smaller fraction of CA125-deficient ovarian cancers expressed DF3 (95%), vascular endothelial growth factor (VEGF) (81%), MUC1 (62%), mesothelin (MES) (34%), HE4 (32%), and CA19-9 (29%). When reactivity with normal tissues was considered, however, MES and HE4 showed the greatest specificity. Differential expression was also found for HK10, OPN, DF3, and MUC1.


CONCLUSIONS
At the level of tissue expression, each of 10 potential serum markers could be detected in 29-100% of ovarian cancers that had low or absent expression of CA125. Several markers exhibited more intense expression in cancers than in normal organs. Further investigation is needed to demonstrate complementary expression of markers in serum.
Rosen
Daniel G
DG
Department of Pathology, University of Texas M.D. Anderson Cancer Center, Box 355, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Wang
Lin
L
Atkinson
J Neeley
JN
Yu
Yinhua
Y
Lu
Karen H
KH
Diamandis
Eleftherios P
EP
Hellstrom
Ingegerd
I
Mok
Samuel C
SC
Liu
Jinsong
J
Bast
Robert C
RC
D000941:Antigens / Q000096:biosynthesis / Q000097:blood; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000097:blood; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000097:blood*; D018394:CA-125 Antigen / Q000096:biosynthesis* / Q000097:blood; D018395:CA-19-9 Antigen / Q000096:biosynthesis / Q000097:blood; D062465:Claudin-3; D003537:Cystadenoma / Q000097:blood / Q000378:metabolism; D030501:Epididymal Secretory Proteins / Q000096:biosynthesis / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D058851:GPI-Linked Proteins; D006023:Glycoproteins / Q000096:biosynthesis / Q000097:blood; D006801:Humans; D007150:Immunohistochemistry; D007610:Kallikreins / Q000096:biosynthesis / Q000097:blood; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000097:blood; D008565:Membrane Proteins / Q000096:biosynthesis / Q000097:blood; D000090204:Mesothelin; D008875:Middle Aged; D018396:Mucin-1; D009077:Mucins / Q000096:biosynthesis / Q000097:blood; D009367:Neoplasm Staging; D053495:Osteopontin; D010051:Ovarian Neoplasms / Q000097:blood* / Q000378:metabolism* / Q000473:pathology; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000097:blood; D023083:beta-Defensins
D000941:Antigens; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D018395:CA-19-9 Antigen; C568122:CLDN3 protein, human; D062465:Claudin-3; C426184:DEFB126 protein, human; D030501:Epididymal Secretory Proteins; D058851:GPI-Linked Proteins; D006023:Glycoproteins; C060192:MUC1 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018396:Mucin-1; D009077:Mucins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D042461:Vascular Endothelial Growth Factor A; D023083:beta-Defensins; D053495:Osteopontin; C100936:KLK10 protein, human; C103551:KLK6 protein, human; D007610:Kallikreins; D000090204:Mesothelin