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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.
Hum Pathol. 2009 Apr; 40(4):527-37.HP

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.

Authors+Show Affiliations

Division of Pathology, Norwegian Radium Hospital, Rikshospitalet Medical Center, N-0310 Oslo, Norway.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19121847

Citation

Slipicevic, Ana, et al. "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." Human Pathology, vol. 40, no. 4, 2009, pp. 527-37.
Slipicevic A, Øy GF, Askildt IC, et al. 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. Hum Pathol. 2009;40(4):527-37.
Slipicevic, A., Øy, G. F., Askildt, I. C., Holth, A., Hellesylt, E., Flørenes, V. A., & Davidson, B. (2009). 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. Human Pathology, 40(4), 527-37. https://doi.org/10.1016/j.humpath.2008.10.003
Slipicevic A, et al. 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. Hum Pathol. 2009;40(4):527-37. PubMed PMID: 19121847.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Slipicevic,Ana, AU - Øy,Geir Frode, AU - Askildt,Inger Cecilie, AU - Holth,Arild, AU - Hellesylt,Ellen, AU - Flørenes,Vivi Ann, AU - Davidson,Ben, Y1 - 2009/01/03/ PY - 2008/07/29/received PY - 2008/09/27/revised PY - 2008/10/01/accepted PY - 2009/1/6/entrez PY - 2009/1/6/pubmed PY - 2009/4/22/medline SP - 527 EP - 37 JF - Human pathology JO - Hum Pathol VL - 40 IS - 4 N2 - 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. SN - 1532-8392 UR - https://www.unboundmedicine.com/medline/citation/19121847/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0046-8177(08)00451-6 DB - PRIME DP - Unbound Medicine ER -