HLA-G is a potential tumor marker in malignant ascites.
OBJECTIVE
Molecular approaches as supplements to cytological examination of malignant ascites may play an important role in the clinical management of cancer patients. HLA-G is a potential tumor-associated marker and that one of its isoforms, HLA-G5, produces a secretory protein. This study is to assess the clinical utility of secreted HLA-G levels in differential diagnosis of malignant ascites.


METHODS
We used ELISA to assess whether secretory HLA-G (sHLA-G) could serve as a marker of malignant ascites in ovarian and breast carcinomas, which represent the most common malignant tumors causing ascites in women.


RESULTS
On the basis of immunohistochemistry, 45 (61%) of 74 ovarian serous carcinomas and 22 (25%) invasive ductal carcinomas of the breast demonstrated HLA-G immunoreactivity ranging from 2 to 100% of the tumor cells. HLA-G staining was not detected in a wide variety of normal tissues, including ovarian surface epithelium and normal breast tissue. Revese transcription-PCR demonstrated the presence of HLA-G5 isoform in all of the tumor samples expressing HLA-G. ELISA was performed to measure the sHLA-G in 42 malignant and 18 benign ascites supernatants. sHLA-G levels were significantly higher in malignant ascites than in benign controls (P < 0.001). We found that the area under the receiver-operating characteristic curve for sHLA-G was 0.95 for malignant versus benign ascites specimens. At 100% specificity, the highest sensitivity to detect malignant ascites was 78% (95% confidence interval, 68-88%) at a cutoff of 13 ng/ml.


CONCLUSIONS
Our findings suggest that measurement of sHLA-G is a useful molecular adjunct to cytology in the differential diagnosis of malignant versus benign ascites.
Singer
Gad
G
Department of Pathology, Johns Hopkins University Medical Institutions, Baltimore Maryland 21231, USA.
Rebmann
Vera
V
Chen
Yu-Chi
YC
Liu
Hsu-Tai
HT
Ali
Syed Z
SZ
Reinsberg
Jochen
J
McMaster
Michael T
MT
Pfeiffer
Kerstin
K
Chan
Daniel W
DW
Wardelmann
Eva
E
Grosse-Wilde
Hans
H
Cheng
Chih-Chien
CC
Kurman
Robert J
RJ
Shih
Ie-Ming
IeM
D001201:Ascites / Q000175:diagnosis / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000737:chemistry / Q000175:diagnosis / Q000378:metabolism*; D044584:Carcinoma, Ductal / Q000737:chemistry / Q000175:diagnosis / Q000378:metabolism; D016022:Case-Control Studies; D018293:Cystadenoma, Serous / Q000737:chemistry / Q000175:diagnosis / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000175:diagnosis / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I