Panel of markers can accurately predict endometriosis in a subset of patients.
OBJECTIVE
To evaluate whether a combination of putative markers of inflammation and CA-125 could serve as a multiple-marker screening test for endometriosis in a heterogeneous population of patients.


METHODS
Case-control evaluation of a diagnostic test.


METHODS
University medical center.


METHODS
Consenting women of reproductive age undergoing laparoscopy for indications of pain, infertility, elective tubal ligation, tubal reanastomosis, or other benign indications.


METHODS
Diagnostic laparoscopy and peripheral venipuncture.


METHODS
Serum concentrations of interleukin-6, tumor necrosis factor-alpha, macrophage migration inhibitory factor, macrophage chemotactic protein-1, interferon-gamma, leptin, and CA-125 measured by using ELISA assays; surgical staging of endometriosis.


RESULTS
Concentrations of the seven markers were compared between the 63 women with surgically confirmed stage II-IV endometriosis and 78 women who were surgically confirmed to be free of endometriosis. The individual diagnostic performance of each of the markers, based on receiver operating characteristic curves, was poor. When combinations of markers were evaluated by using classification tree analysis, a three-marker panel of CA-125, macrophage chemotactic protein-1, and leptin could diagnose 51% of subjects as to the presence of endometriosis with 89% accuracy. A four-marker panel of CA-125, macrophage chemotactic protein-1, leptin, and macrophage migration inhibitory factor could diagnose 48% of subjects with 93% accuracy. The remaining subjects would have no definitive diagnosis on the basis of the algorithm and would need to undergo standard evaluation.


CONCLUSIONS
This large study evaluates the combined use of putative serum markers for the diagnosis of endometriosis, rather than the use of each singly. Using the serum concentration of four markers in a two-tiered decision rule, nearly half of the subjects in this population would have been diagnosed (and could have avoided surgery) with 93% accuracy.
Seeber
Beata
B
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
Sammel
Mary D
MD
Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
Fan
Xuejun
X
Center for Research in Reproduction and Women's Health, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
Gerton
George L
GL
Center for Research in Reproduction and Women's Health, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
Shaunik
Alka
A
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
Chittams
Jesse
J
Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
Barnhart
Kurt T
KT
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. Electronic address: kbarnhart@mail.obgyn.upenn.edu.
D000293:Adolescent; D000328:Adult; D000465:Algorithms; D015415:Biomarkers / Q000097:blood; D018394:CA-125 Antigen / Q000097:blood*; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000097:blood; D016207:Cytokines / Q000097:blood*; D004715:Endometriosis / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D019746:Intramolecular Oxidoreductases / Q000097:blood; D020738:Leptin / Q000097:blood; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood; D008875:Middle Aged; D011237:Predictive Value of Tests; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015415:Biomarkers; D018394:CA-125 Antigen; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D015850:Interleukin-6; D020738:Leptin; D008263:Macrophage Migration-Inhibitory Factors; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human