This hypothesis explain that cancer origin could be due to low hypoxic conditions in the peripheral zones of benign tumors which might up-regulate the expression of IGF2, and, consequently, trophoblastic genes.
On the contrary, the expression of <i>IGF-1R</i>, mediating the IGF-2 effects <i>in vivo</i>, was more discriminant between malignant (overexpression) and benign tumors.
To further investigate this role, the IGF/IGF-binding protein (IGFBP) system was analyzed in 18 adrenocortical tumors, classified into 2 groups on the basis of their IGF-II messenger ribonucleic acid (mRNA) content (group 1, normal IGF-II mRNA content, mostly benign tumors; group 2, high IGF-II mRNA content, mostly malignant tumors).
Abnormalities of the 11p15 region as LOH (loss of the maternal allele and duplication of the paternal allele) and/or IGF-II gene overexpression are frequent features of the malignant state and were found in 27 of 29 (93.1%) of the malignant tumors and in only 3 of 35 (8.6%) of the benign tumors.