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Diagnostic and prognostic role of the insulin growth factor pathway members insulin-like growth factor-II and insulin-like growth factor binding protein-3 in serous effusions
- Source :
- Human pathology. 40(4)
- Publication Year :
- 2008
-
Abstract
- We recently reported on higher expression of the insulin-like growth factor pathway genes IGF-II and IGFBP3 in serous ovarian/peritoneal carcinoma compared to malignant peritoneal mesothelioma. The present study analyzed the diagnostic and clinical role of these proteins in serous effusions. Effusions (n = 327), including 294 carcinomas (205 ovarian, 48 breast, 17 cervical/endometrial, 12 lung, 12 gastrointestinal/genitourinary) and 33 malignant mesotheliomas, were immunostained for insulin-like growth factor-II and insulin-like growth factor binding protein-3. Surgical ovarian carcinoma (n = 124) and peritoneal mesothelioma (n = 18) specimens were additionally studied. Insulin-like growth factor binding protein-3 levels were measured in 148 effusion supernatants (114 ovarian carcinomas, 18 breast carcinomas, 16 mesotheliomas) using enzyme-linked immunosorbent assay. Insulin-like growth factor binding protein-3 promoter methylation was analyzed in 11 ovarian carcinoma effusions. Insulin-like growth factor binding protein-3 (P = .002) and insulin-like growth factor-II (P < .001) expression by immunohistochemistry was significantly higher in carcinomas compared to mesotheliomas, with diagnostic sensitivity of 77% and 70% and specificity of 55% and 70%, respectively. In surgical specimens, insulin-like growth factor binding protein-3 expression was higher in ovarian carcinomas compared to peritoneal mesotheliomas (P = .007), whereas insulin-like growth factor-II expression was comparable (P = .505). Insulin-like growth factor binding protein-3 levels by enzyme-linked immunosorbent assay were comparable in the 3 analyzed cancer types. Insulin-like growth factor binding protein-3 promoter methylation was found in 6 of 11 effusions. High insulin-like growth factor binding protein-3 expression in prechemotherapy and high insulin-like growth factor-II expression in postchemotherapy ovarian carcinoma effusions correlated with poor overall survival (P = .031 and P = .024, respectively). Insulin-like growth factor-II expression in postchemotherapy effusions was an independent prognostic factor in Cox multivariate analysis (P = .04). In conclusion, insulin-like growth factor-II and insulin-like growth factor binding protein-3 are more frequently expressed in metastatic carcinomas compared to mesothelioma in effusions but are less specific than currently used markers. Insulin-like growth factor-II and insulin-like growth factor binding protein-3 may be novel prognostic markers in metastatic ovarian carcinoma.
- Subjects :
- Adult
Mesothelioma
Pathology
medicine.medical_specialty
medicine.medical_treatment
IGFBP3
Enzyme-Linked Immunosorbent Assay
Kaplan-Meier Estimate
Polymerase Chain Reaction
Sensitivity and Specificity
Insulin-like growth factor-binding protein
Pathology and Forensic Medicine
Diagnosis, Differential
Insulin-like growth factor
Insulin-Like Growth Factor II
Ovarian carcinoma
medicine
Biomarkers, Tumor
Ascitic Fluid
Humans
Aged
Aged, 80 and over
Ovarian Neoplasms
biology
business.industry
Growth factor
Carcinoma
Middle Aged
medicine.disease
Prognosis
Immunohistochemistry
Insulin-Like Growth Factor Binding Proteins
Serous fluid
Insulin-Like Growth Factor Binding Protein 3
Tissue Array Analysis
Insulin-like growth factor 2
biology.protein
Cancer research
Female
business
Subjects
Details
- ISSN :
- 15328392
- Volume :
- 40
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Human pathology
- Accession number :
- edsair.doi.dedup.....15bc9bf50cf4da571e7f67d182f1c97b