Author(s): Singer G, Rebmann V, Chen YC, Liu HT, Ali SZ,
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Abstract 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.
This article was published in Clin Cancer Res
and referenced in Journal of Clinical & Cellular Immunology