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HLA-G Is a Potential Tumor Marker in Malignant Ascites

Department of Pathology [G. S., Y-C. C., S. Z. A., D. W. C., C-C. C., R. J. K., I-M. S.], and Department of Epidemiology [H-T. L., Johns Hopkins University Medical Institutions, Baltimore Maryland 21231; Department of Immunology, University Hospital of Essen, Essen, Germany [V. R., H. G-W.]; Departments of Gynecology and Obstetrics [J. R., K. P.], and Department of Pathology [E. W.], University of Bonn, Bonn, Germany; and Department of Stomatology, University of California, San Francisco, California [M. T. M.]

Purpose: 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.

Experimental Design: 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.

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