Integrin-linked kinase, phosphorylated AKT and the prognosis of malignant pleural mesothelioma §

Objective: Integrin-linked kinase (ILK) is a cell membrane-bound molecule implicated in the metastatic progression of many tumour types. It phosphorylates the downstream target AKT (phosphorylated AKT, pAKT), and, by doing this, it activates anti-apoptotic pathways. We have recently shown ILK expression in malignant pleural mesothelioma (MPM). To determine whether ILK expression in MPM is connected with pAKT expression, and whether ILK and pAKT expression have any influence on the patient’s prognosis, we correlated ILK and pAKT expression, as assessed by immunohistochemistry, with disease-related survival in a retrospective cohort of 80 MPM patients. Material and methods: The paraffinspecimensof80MPMcasestreatedfrom1990to2006(52surgicalcases,28conservativecases)havebeenretrievedfromthearchive.The median (range) patients’ age was 62 (28—83 years) years; the male-to-female ratio was 3:1. Fifty percent of the patients had an epitheloid subtype. The samples have been stained with anti-ILK as well as with anti-pAKTand scored by two independent pathologists. Intensity of ILK and pAKTexpressionhasbeencorrelatedwithdisease-relatedsurvival.Results:Intotal,73of80(91%)MPMsamplesexpressedILK;65of74(88%)MPM samples expressed pAKT. Comparing the 5-year disease-related survival according to ILKor pAKTexpression, no statistically significant difference could be found between ILK and pAKTexpressing or non-expressing patients. However, in the subgroup of conservatively treated MPM patients, those with strong ILKexpression had a longer 5-year disease-related survival (p < 0.0001). In total, the only prognostic factor across all ILK, pAKT and therapy subgroups was the histological subtype (p = 0.01). The prognostic significance of the histological subtype has been confirmed in multivariate analysis (p = 0.005). Conclusion: The expression of ILKin MPM is connected with the expression of the downstream target pAKT, but neitherILKnorpAKTexpressionhasameasurableinfluenceonthepatient’sprognosis,exceptforcertainsubgroupsofMPM.However,toshedlight