ILK (?1-integrin-linked protein kinase): a novel immunohistochemical marker for Ewing's sarcoma and primitive neuroectodermal tumour

Abstract

ILK (beta1-integrin-linked protein kinase) is a recently identified 59-kDa serine/threonine protein kinase that interacts with the cytoplasmic domain of the beta1-integrin containing four ankyrin-like repeats. We have developed a polyclonal antibody against ILK and explored the ILK immunoreactivity in normal human cells and tissues. ILK was mainly expressed in cardiac muscle and skeletal muscles. Surprisingly, ILK expression was observed in Ewing's sarcoma (ES; 100%), primitive neuroectodermal tumour (PNET; 100%), medulloblastoma (100%), and neuroblastoma (33.3%), whereas other small round cell sarcomas were not stained by the anti-ILK antibody. These results suggest that ILK could be a novel marker for tumours with primitive neural differentiation. Our findings support the notion that ES is a tumour that is closely related to PNET and that both originate from the neuroectoderm. ILK may be a sensitive and specific immunohistochemical marker and useful for the positive identification of ES and PNET in formalin-fixed, paraffin-embedded tissue sections.

Cloning of an isoform of integrin-linked kinase (ILK) that is upregulated in HT-144 melanoma cells following TGF-β1 stimulation

“…ILK has been shown to be expressed in a wide spectrum of human (Hannigan et al, 1996) and mouse tissues ) when studied at the mRNA level. In contrast, when exploring the ILK immunoreactivity in normal human cells and tissues, as well as various tumor cell types, Chung et al (1998) found that ILK was expressed mainly in myocardiac cells and skeletal muscle ®bers. Among the tumors tested, Ewing's sarcoma (ES), primitive neuroectodermal tumors (PNET) and medulloblastomas revealed strong ILK immunoreactivity, while other small round cell sarcomas were negative, suggesting a value for ILK as a speci®c diagnostic marker of tumors with primitive neural di erentiation.…”

“…With the selective expression of ILK-2 in some tumor cells, as shown here, and the cross-reactivity of anti-ILK antibodies with ILK-1 and ILK-2, further studies will be of interest to test which isoform of ILK is expressed in ES and PNET tumors. Also the discrepancy between ILK mRNA expression and ILK antigen expression in normal versus malignant tissues (Chung et al, 1998) could potentially be explained by a higher stability of ILK-2, or a higher a nity of the anti-ILK antibody for ILK-2.…”

ILKAP regulates ILK signaling and inhibits anchorage-independent growth

“…Consistent with these transformation models, elevated ILK protein and activity levels are seen in Ewing's Sarcoma (Chung et al, 1998), and in precancerous colonic polyps (Marotta et al, 2001). Elevated ILK expression and activity shows a strong positive correlation with prostate tumor grade (Graff et al, 2001), is associated with metastatic gastric carcinoma (Ito et al, 2003) and correlates with poor patient outcome in malignant melanoma (Dai et al, 2003), altogether suggesting that ILK dysregulation contributes to early and late stages of tumor development.…”

Inhibition of ILK in PTEN-mutant human glioblastomas inhibits PKB/Akt activation, induces apoptosis, and delays tumor growth

“…Integrinlinked kinase has been associated with cell proliferation in ovarian cancer cells (Cruet-Hennequart et al, 2003), ILK expression has also been shown to increase with prostate tumor grade (Graff et al, 2001), and is a potential diagnostic marker for Ewing's sarcoma and primitive ectodermal tumors (Chung et al, 1998). It is clear that ILK plays a major role in cancer progression and glioblastomas are part of ILK's oncogenic repertoire.…”