Comparison of Serum Human Epididymis Protein 4 with Cancer Antigen 125 as a Tumor Marker in Patients with Malignant and Nonmalignant Diseases J.M. Escudero,
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Comparison of Serum Human Epididymis Protein 4 with Cancer Antigen 125 as a Tumor Marker in Patients with Malignant and Nonmalignant Diseases
J.M. Escudero, J.M. Auge, X. Filella, A. Torne, J. Pahisa, and R. Molina
• Encoded by a gene located in chromosome 20q12–13.1
• Overexpressed in ovarian cancer, but also in pulmonary, endometrial, and breast cancers and mesotheliomas
• Previous studies have suggested that HE4 has diagnostic sensitivity similar to that of CA 125, but an increased diagnostic specificity in patients with gynecologic malignancies compared with those with benign gynecologic disease
• Little is known about HE4 specificity in other benign and malignant conditions
Laboratory methods:• HE4 and CA125 were determined by use of a
chemiluminescent enzyme immunoassay on an Architect® (Abbott Laboratories)
• Creatinine was measured by use of an alkaline picrate kinetic method on an Advia® 2400 (Siemens Medical Solutions Diagnostics)
Statistical analysis:• Data reported herein as median (range). Tumor marker
concentrations were compared by use of the Kruskall-Wallis and Mann-Whitney tests and ROC curves were compared by the DeLong mathematical model (SPSS 15.0, IBM-SPSS)
Table 1. Serum concentrations of HE4 and CA125 in healthy people and patients with benign diseases.a p=0.01; b p=0.005; c p=0.001; d p=0.023. HE4 serum concentrations in healthy individuals were related to gender and age with significantly higher concentrations in postmenopausal women (p<0.02). Renal failure and effusions were the most important sources of false positive HE4 serum concentrations. HE4 must be interpreted carefully in patients with renal failure.
Figure 1. ROC curves for (A), HE4 and CA125 for the diagnosis of malignancy (excluding renal failure), comparing active cancer and patients with benign diseases; (B), HE4 and CA125 for the diagnosis of ovarian cancer (excluding renal failure), comparing patients with ovarian cancer and other diseases (benign and malignant).
Results (cont’d)Results (cont’d)
HE4 showed a higher specificity than CA 125 with a higher area under the curve in both situations, for diagnosis of cancer or ovarian cancer
Table 2. Serum concentrations of HE4 and CA125 in patients with active malignancy. a p=0.001 with both markers; b p=0.001 with HE4.
The highest HE4 serum concentrations were found in patients with ovarian cancer but also were found in other malignancies such lung and endometrial cancer. In contrast, CA125 was widely distributed.
Table 3. Serum concentrations of HE4 and CA125 in patients with ovarian cancer [excluding patients with renal failure or creatinine >1.3 mg/dl (>115µmol/L)] subdivided according to tumor stage and histological type.
Both tumor markers were clearly related to stage and histology, with significantly higher serum concentrations in advanced stage and in non-mucinous malignancies CA 125 showed a higher sensitivity in advanced stages and slightly higher HE4 sensitivity was obtained in early stages Combination of both tumor markers improved the detection of ovarian cancer
Figure 2. ROC curves for (A), HE4 and CA125 for the diagnosis of gynecological cancer (excluding renal failure), comparing gynecological cancer and patients with benign gynecological diseases; (B), HE4 and CA125 for the diagnosis of ovarian cancer (excluding renal failure), comparing patients with ovarian cancer and other gynecological diseases (benign and malignant)
Results (cont’d)Results (cont’d)
HE4 showed a better area under the curve in both situations, in the diagnosis of gynecologic cancer vs. benign gynecologic diseases and in the diagnosis of ovarian cancer
Renal failure and effusions were the most important sources of false positive HE4 serum concentrations. HE4 must be interpreted carefully in patients with renal failure.
HE4 diagnostic specificity was higher than CA125 in non-malignant diseases, both gynecological or non-gynecological.
The highest HE4 serum concentrations were found in patients with ovarian cancer but HE4 also may be found in patients with lung cancer or endometrial cancer. By contrast CA125 was widely distributed.
HE4 and CA125 were diagnostically sensitive tumor markers with a clear relationship to tumor stage and histology, with the lowest concentrations in mucinous malignancies.
HE4 diagnostic sensitivity was better than CA125 in early stages of ovarian cancer.