Division of Thoracic Surgery, Otto Wagner Hospital, Vienna, Austria.
Eur J Cardiothorac Surg. 2011 Feb;39(2):180-4. doi: 10.1016/j.ejcts.2010.05.007. Epub 2010 Jul 1.
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.
The paraffin specimens of 80 MPM cases treated from 1990 to 2006 (52 surgical cases, 28 conservative cases) have been retrieved from the archive. 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-pAKT and scored by two independent pathologists. Intensity of ILK and pAKT expression has been correlated with disease-related survival.
In total, 73 of 80 (91%) MPM samples expressed ILK; 65 of 74 (88%) MPM samples expressed pAKT. Comparing the 5-year disease-related survival according to ILK or pAKT expression, no statistically significant difference could be found between ILK and pAKT expressing or non-expressing patients. However, in the subgroup of conservatively treated MPM patients, those with strong ILK expression 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).
The expression of ILK in MPM is connected with the expression of the downstream target pAKT, but neither ILK nor pAKT expression has a measurable influence on the patient's prognosis, except for certain subgroups of MPM. However, to shed light on the true prognostic impact of ILK and pAKT expression in MPM, prospective trials are needed.
整合素连接激酶（ILK）是一种与多种肿瘤类型的转移进展有关的细胞膜结合分子。它使下游靶标 AKT（磷酸化 AKT，pAKT）磷酸化，并通过这种方式激活抗凋亡途径。我们最近在恶性胸膜间皮瘤（MPM）中发现了 ILK 的表达。为了确定 MPM 中的 ILK 表达是否与 pAKT 表达有关，以及 ILK 和 pAKT 表达是否对患者的预后有任何影响，我们通过免疫组织化学方法，将 80 例 MPM 患者的石蜡标本（1990 年至 2006 年治疗的 52 例手术病例和 28 例保守病例）与疾病相关的生存情况相关联。患者的中位（范围）年龄为 62（28-83 岁）岁；男女比例为 3:1。50%的患者为上皮样亚型。对这些样本进行了抗 ILK 以及抗 pAKT 的染色，并由两位独立的病理学家进行评分。ILK 和 pAKT 表达的强度与疾病相关的生存情况相关。
总共，80 例 MPM 样本中的 73 例（91%）表达了 ILK；74 例 MPM 样本中的 65 例（88%）表达了 pAKT。根据 ILK 或 pAKT 的表达比较 5 年疾病相关生存率，在表达或不表达 ILK 和 pAKT 的患者之间未发现统计学显著差异。然而，在保守治疗的 MPM 患者亚组中，那些 ILK 表达较强的患者有更长的 5 年疾病相关生存率（p<0.0001）。总的来说，在所有 ILK、pAKT 和治疗亚组中，唯一的预后因素是组织学亚型（p=0.01）。组织学亚型的预后意义已在多变量分析中得到证实（p=0.005）。
MPM 中的 ILK 表达与下游靶标 pAKT 的表达有关，但 ILK 和 pAKT 的表达都不能对患者的预后产生可衡量的影响，除了 MPM 的某些亚组。然而，为了阐明 ILK 和 pAKT 在 MPM 中的表达对预后的真正影响，需要进行前瞻性试验。
