Prognostic Value of Protein IMP3 Expression in Cervical Cancer

Molecular biomarkers could selectively identify patients with a more unfavorable clinical course. One of these biomarkers is IMP3 - insulin-like growth factor II mRNA binding protein.

The IGF group is a complex regulatory network at the cellular and substantial levels and plays a key physiological role in the development of the organism and the maintenance of normal cellular function during fetal and postnatal life. Overexpression of growth factors and their receptors is a common event during carcinogenesis. The IGF signaling system is under strict control of the normal physiological state and a deviation in this delicate balance can be a trigger for many molecular events leading to the development of malignancy. One member of the IGF system is the insulin-like growth factor II mRNA binding protein (IMP) which has been found to be an activator of IGF-II translation mRNA thus gaining a dominant role in controlling IGF-II-dependent cell proliferation.

The IMP protein family contains 3 proteins (IMP1, IMP2, IMP3). IMP3 is normally expressed in fetal tissues during embryogenesis. In adulthood, it appears as an oncoprotein that is expressed only in tumor tissues without the presence in the surrounding (adjacent) benign tissue. Previous in vitro studies have shown that IMP3 stimulates tumor cell proliferation by activating IGF II translation and adhesion and invasion via adhesion molecules and matrix metalloproteinases 1.

The results of recent research on cervical cancer and its precancerous lesions have linked the expression of IMP3 protein to cervical dysplasia and the possibility of severe cervical dysplasia (CIN III) progressing to squamous cell carcinoma. A higher expression of IMP3 protein was found in the cytoplasms of severe cervical dysplasia (CIN III) cells and invasive tumor cells compared to CIN I and CIN II change cells. The sensitivity of IMP3 expression in tumor cells was 96%. In preparations that were IMP3 negative, no further monitoring and treatment revealed squamous cell carcinoma. Further analyzes indicated the possibility of determining IMP3 expression on first cervical biopsy specimens in patients with HSIL lesions as a biomarker to detect a subset of patients in whom lesion invasiveness can be expected.

Based on previous studies, a monoclonal antibody specific for IMP3 has been developed and is successfully used in routine immunohistochemical methods that study the expression of IMP3 proteins in various malignancies. It has recently been found that the expression of IMP3 protein is associated with a more aggressive clinical course and a less favorable outcome in both gynecological and malignant diseases of other organ systems.