HLA-G is a potential tumor marker in malignant ascites

Gad Singer, Vera Rebmann, Yu Chi Chen, Hsu Tai Liu, Syed Z Ali, Jochen Reinsberg, Michael T. McMaster, Kerstin Pfeiffer, Daniel Wan-Yui Chan, Eva Wardelmann, Hans Grosse-Wilde, Chih Chien Cheng, Robert J Kurman, Ie Ming Shih

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)4460-4464
Number of pages5
JournalClinical Cancer Research
Volume9
Issue number12
StatePublished - Oct 1 2003

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HLA-G Antigens
Tumor Biomarkers
Ascites
Neoplasms
Differential Diagnosis
Enzyme-Linked Immunosorbent Assay
Carcinoma, Ductal, Breast
ROC Curve
Cell Biology

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Singer, G., Rebmann, V., Chen, Y. C., Liu, H. T., Ali, S. Z., Reinsberg, J., ... Shih, I. M. (2003). HLA-G is a potential tumor marker in malignant ascites. Clinical Cancer Research, 9(12), 4460-4464.

HLA-G is a potential tumor marker in malignant ascites. / Singer, Gad; Rebmann, Vera; Chen, Yu Chi; Liu, Hsu Tai; Ali, Syed Z; Reinsberg, Jochen; McMaster, Michael T.; Pfeiffer, Kerstin; Chan, Daniel Wan-Yui; Wardelmann, Eva; Grosse-Wilde, Hans; Cheng, Chih Chien; Kurman, Robert J; Shih, Ie Ming.

In: Clinical Cancer Research, Vol. 9, No. 12, 01.10.2003, p. 4460-4464.

Research output: Contribution to journalArticle

Singer, G, Rebmann, V, Chen, YC, Liu, HT, Ali, SZ, Reinsberg, J, McMaster, MT, Pfeiffer, K, Chan, DW-Y, Wardelmann, E, Grosse-Wilde, H, Cheng, CC, Kurman, RJ & Shih, IM 2003, 'HLA-G is a potential tumor marker in malignant ascites', Clinical Cancer Research, vol. 9, no. 12, pp. 4460-4464.
Singer G, Rebmann V, Chen YC, Liu HT, Ali SZ, Reinsberg J et al. HLA-G is a potential tumor marker in malignant ascites. Clinical Cancer Research. 2003 Oct 1;9(12):4460-4464.
Singer, Gad ; Rebmann, Vera ; Chen, Yu Chi ; Liu, Hsu Tai ; Ali, Syed Z ; Reinsberg, Jochen ; McMaster, Michael T. ; Pfeiffer, Kerstin ; Chan, Daniel Wan-Yui ; Wardelmann, Eva ; Grosse-Wilde, Hans ; Cheng, Chih Chien ; Kurman, Robert J ; Shih, Ie Ming. / HLA-G is a potential tumor marker in malignant ascites. In: Clinical Cancer Research. 2003 ; Vol. 9, No. 12. pp. 4460-4464.
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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.",
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T1 - HLA-G is a potential tumor marker in malignant ascites

AU - Singer, Gad

AU - Rebmann, Vera

AU - Chen, Yu Chi

AU - Liu, Hsu Tai

AU - Ali, Syed Z

AU - Reinsberg, Jochen

AU - McMaster, Michael T.

AU - Pfeiffer, Kerstin

AU - Chan, Daniel Wan-Yui

AU - Wardelmann, Eva

AU - Grosse-Wilde, Hans

AU - Cheng, Chih Chien

AU - Kurman, Robert J

AU - Shih, Ie Ming

PY - 2003/10/1

Y1 - 2003/10/1

N2 - 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.

AB - 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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