Evaluation of plasma insulin-like growth factor binding protein-2 as a marker for adrenocortical tumors

Abstract

Objective: Recent studies have pointed to the role of the IGF system in the pathogenesis of adrenocortical tumors, and it was shown recently that malignant adrenocortical tumors exhibit a high insulin-like growth factor binding protein (IGFBP)-2 content. Circulating markers specific for adrenocortical carcinoma are needed and the aim of this study was to evaluate plasma IGFBP-2 as a marker for these malignant tumors. Methods: Plasma IGFBP-2 was determined in 51 patients referred to our institutions for adrenocortical tumors. Fifteen patients were in complete remission (group 1), eight patients had preoperative localized tumors (group 2) and 28 patients had metastatic tumors (group 3). Thirty-six healthy volunteers constituted a control group. Results: There was no significant difference in plasma IGFBP-2 concentration between healthy controls and patients with complete remission or localized tumors. In contrast, patients with metastatic disease had significantly higher IGFBP-2 plasma levels than the control group P , 0X001X IGFBP-2 levels in patients with metastatic disease were inversely correlated with survival R 2 0X308; P 0X0026X In patients with localized tumors, there was no correlation between plasma IGFBP-2 concentration and tumor size or histological features. Analysis of individual IGFBP-2 concentrations showed that five patients (17.8%) with metastatic tumors had normal IGFBP-2 levels and two patients (13.3%) in complete remission had high plasma IGFBP-2 levels. The influence of nutrition, hormone secretion and treatment on IGFBP-2 levels was examined. Nutritional status was evaluated by determining IGF-I levels and was found to be normal in 16 patients (61.5%) with high IGFBP-2 levels, suggesting that malnutrition was not responsible for the high IGFBP-2 concentrations in these patients. IGFBP-2 levels did not differ significantly according to tumor secretion or mitotane treatment. In a follow-up study, plasma IGFBP-2 concentration remained stable in patients with complete remission or stabilized disease and was a late marker of tumor progression in patients with progressive metastatic disease. Conclusions: These results indicate that plasma IGFBP-2 is elevated in patients with malignant adrenocortical tumors and that the major factor affecting IGFBP-2 levels in these patients is tumor stage. However, plasma IGFBP-2 was less sensitive than expected for a tumor marker, which may limit its value in the diagnosis and follow-up of adrenocortical carcinoma.

Gene expression profiling identifies potential relevant genes in alveolar rhabdomyosarcoma pathogenesis and discriminates PAX3‐FKHR positive and negative tumors

“…IGFBP2 was reported to be markedly overexpressed in many tumors and tumors cell lines. [59][60][61] This elevated expression of IGFBP2 might be promoted by autocrine/paracrine stimulation via IGF2, which is often secreted in tumors in large quantities. 62,63 In addition, the expression level of IGFBP2 was found altered in some rhabdomyosarcoma cell lines 15 and also in the RMS SAGE library.…”

Integrin-mediated action of insulin-like growth factor binding protein-2 in tumor cells

“…In tumor cells, overexpression of IGFBP-2 promotes growth tolerance against metabolic stress, while hindering apoptosis in these cells (Oh & Rosenfeld 1999, Hoeflich et al 2000a. Clinical observations on patients with tumors of the brain, adrenal cortex, prostate and other organs further show the direct effects of IGFBP-2 on tumor progression (Miller 1994, Ho & Baxter 1997, Boulle et al 2001, Elmlinger et al 2001a. All of these studies reveal a clear relationship between the degree of clinical malignancy and the degree of expression, or serum levels, of IGFBP-2.…”

“…IGFBP-2 has been reported to be markedly overexpressed in many tumors and tumor cell lines (Kanety et al 1993, Boulle et al 2001, Elmlinger et al 2001a. This elevated expression of IGFBP-2 might be promoted by autocrine/paracrine stimulation via IGF-II-and/or pro-IGF-forms, which tumors often secrete in large quantities (Yang et al 1996, Duguay et al 1998, Elmlinger et al 1999, Elmlinger et al 2001b.…”

Primary pigmented nodular adrenocortical disease reveals insulin-like growth factor binding protein-2 regulation by protein kinase A

“…Altogether these findings support a model of PPNAD in which PRKAR1A mutation decreases PKA-I activity that in turn leads to IGFBP-2 induction and enhanced adrenocortical cell proliferation. This model may have implications for adrenocortical tumors as well; IGFBP-2 over-expression has been reported in sporadic adrenocortical tumors [8][9][10][11], and PRKAR1A-inactivating mutations, down-regulation and somatic allelic loss of the 17q22-24 region have also been found in sporadic adrenocortical tumors, especially those presenting with Cushing syndrome [17].…”

“…Over-expression of IGF-II and IGF binding protein (IGFBP)-2 was found in adult sporadic adrenocortical tumors and associated with a malignant phenotype [8]. Plasma IGFBP-2 levels were significantly higher in adults with metastatic adrenocortical disease than normal controls and were inversely correlated with survival [9]. Because IGFBP-2 was not exclusively found in metastatic tumors, however, it was not specific enough to serve as a molecular marker for malignancy.…”