title: HLA-G is a potential tumor marker in malignant ascites.
abstract: 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.
authors.affiliation: Department of Pathology, Johns Hopkins University Medical Institutions, Baltimore Maryland 21231, USA.
authors.forename: Gad
authors.initials: G
authors.lastname: Singer
authors.forename: Vera
authors.initials: V
authors.lastname: Rebmann
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Chen
authors.forename: Hsu-Tai
authors.initials: HT
authors.lastname: Liu
authors.forename: Syed Z
authors.initials: SZ
authors.lastname: Ali
authors.forename: Jochen
authors.initials: J
authors.lastname: Reinsberg
authors.forename: Michael T
authors.initials: MT
authors.lastname: McMaster
authors.forename: Kerstin
authors.initials: K
authors.lastname: Pfeiffer
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Chan
authors.forename: Eva
authors.initials: E
authors.lastname: Wardelmann
authors.forename: Hans
authors.initials: H
authors.lastname: Grosse-Wilde
authors.forename: Chih-Chien
authors.initials: CC
authors.lastname: Cheng
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kurman
authors.forename: Ie-Ming
authors.initials: IeM
authors.lastname: Shih
mesh_terms: 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
chemical_list: D014408:Biomarkers, Tumor; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I