Insulin-like growth factor-binding protein 2 and 5 are differentially regulated in ovarian cancer of different histologic types

Abstract

The family of insulin-like growth factor-binding proteins (IGFBPs) comprises six members, which bind and regulate the functions of insulin-like growth factors. Overexpression of IGFBP2 and IGFBP5 contributes to the invasiveness and progression of several human cancers, but their role and clinical significance in ovarian cancer has not been investigated in detail. We examined IGFBP2 and IGFBP5 expression levels using two tissue microarrays, one containing six normal surface epithelium, six benign serous cysts, 10 serous borderline tumors, eight low-grade, and 20 high-grade serous carcinomas. The other comprising 441 ovarian cancers of different histologic types linked to a clinicopathologic database. Each tumor was sampled in duplicate with a 1.0-mm punch core needle. Immunohistochemical staining was performed using antibodies against IGFBP2 or IGFBP5. The staining intensity was scored semiquantitatively as negative (0), weak (1-10%), moderate (10-50%), or strong (50-100%) using computerized image analysis. Statistical analyses used Fisher's exact test and Kaplan-Meier method. IGFBP2 and IGFBP5 were overexpressed in high-grade serous carcinomas compared to normal surface epithelium, benign serous cysts, serous borderline tumors, or low-grade serous carcinoma. They were differentially expressed in different types of ovarian carcinomas, being more often expressed at high levels in high-grade serous carcinoma, malignant mixed mullerian tumors and undifferentiated carcinoma, and more often expressed at low levels or not at all in clear cell and mucinous carcinomas. We concluded that IGFBP2 and IGFBP5 might play a role in the development of high-grade ovarian serous carcinoma, but not in mucinous or clear cell ovarian carcinomas.

Differential gene expression profiles of invasive and non-invasive non-functioning pituitary adenomas based on microarray analysis

“…IGFBP5 was also overexpressed in our invasive tumors. The product of this gene has been shown to play a role in malignancy, and particularly in breast, ovary, and prostatic cancer (Hwa et al 1997, Schneider et al 2002, Johnson et al 2006, Wang et al 2006a,b, 2008, Nishino et al 2008. However, IGFBP5 protein expression did not differ between invasive and noninvasive NFPAs.…”

Comparative secretome of ovarian serous carcinoma: Gelsolin in the spotlight

“…Furthermore, high expression levels of CSF-1 are associated with poor patient outcome, suggesting that this protein may be a potential biomarker and prognostic factor (20,21). IGFBP-2 also serves a significant role in EOC pathogenesis and may represent an additional serum biomarker with utility in the detection and monitoring of EOC (23,26). HSP-10 is known to serve a role in the mechanism underlying mitochondrial protein-folding.…”

“…These proteins have previously been studied in ovarian cancer cells (19)(20)(21)(22)(23). CSF-1 may serve an important role in ovarian carcinogenesis, as it has the capacity to increase the invasive ability of ovarian cancer cells (24) and to promote metastasis (25).…”

Insulin-like growth factor binding protein 5 suppresses tumor growth and metastasis of human osteosarcoma

“…Additionally, IGFBP5 is downregulated in renal and cervical tumors, but appears to be upregulated in high-grade ovarian carcinoma and thyroid papillary carcinoma (Stolf et al, 2003;Cheung et al, 2005;Takahashi et al, 2005;Wang et al, 2006). These conflicting results may be due to IGFBP5 mediating its effects in both IGF-dependent and IGF-independent pathways (Akkiprik et al, 2008).…”