Dellas Athanassios, Jundt Gernot, Sartorius Gideon, Schneider Mischa, Moch Holger
Department of Pathology, University Hospital Basel, University of Basel, Basel,Switzerland.
Clin Cancer Res. 2009 Apr 1;15(7):2456-62. doi: 10.1158/1078-0432.CCR-08-1732. Epub 2009 Mar 17.
Phosphatase and tensin homologue deleted from chromosome 10 (PTEN) and p27(kip1) proteins are key players of the Akt pathway, which is nutritionally regulated by insulin receptor signaling and influenced by estrogens. In this study, the prognostic relevance of the PTEN/p27(kip1) protein expression in endometrial carcinoma in relationship to the body mass index (BMI) was determined.
BMI and prognosis of 452 surgically treated patients with endometrial carcinoma were correlated with histologic subtype, International Federation of Gynecology and Obstetrics (FIGO) stage, and differentiation grade. The expression of PTEN and p27(kip1) was examined in 257 tumors by immunohistochemistry using a tissue microarray approach.
Lack of PTEN was observed in 136 of 257 (53%) tumors and absence of p27(kip1) expression was observed in 106 of 225 (47%) tumors. Absence of both proteins was significantly associated with well-differentiated tumors [PTEN (P < 0.02) and p27(kip1) (P < 0.009)]. Differentiation grade, tumor stage, and histologic type were independent of an increased BMI. Importantly, tumors of obese women expressed significantly less PTEN (P < 0.008) and less p27(kip1) (P < 0.01) than tumors from nonobese patients. Combined absence of both PTEN and p27(kip1) expression characterized a group of 75 (32%) tumors with favorable clinical outcome, particularly in the FIGO stages I and II (P = 0.003) of obese patients. Cox regression analysis revealed that PTEN/p27(kip1) phenotype, FIGO stage, and histologic grade were independent predictors of prognosis in endometrioid endometrial carcinoma.
Inactivation of PTEN/p27(kip1) proteins is a specific feature in the progression of endometrial carcinoma in obese patients. The phenotype of the combined loss of PTEN/p27(kip1) protein expression in obese patients is associated with a significantly better prognosis in endometrioid endometrial carcinoma.
10号染色体缺失的磷酸酶和张力蛋白同源物（PTEN）及p27（kip1）蛋白是Akt信号通路的关键因子，该通路受胰岛素受体信号的营养调控并受雌激素影响。本研究确定了PTEN/p27（kip1）蛋白表达在子宫内膜癌中与体重指数（BMI）相关的预后意义。
452例接受手术治疗的子宫内膜癌患者的BMI和预后与组织学亚型、国际妇产科联盟（FIGO）分期及分化程度相关。采用组织芯片方法通过免疫组化检测了257例肿瘤中PTEN和p27（kip1）的表达。
257例肿瘤中有136例（53%）观察到PTEN缺失，225例肿瘤中有106例（47%）观察到p27（kip1）表达缺失。两种蛋白均缺失与高分化肿瘤显著相关[PTEN（P < 0.02）和p27（kip1）（P < 0.009）]。分化程度、肿瘤分期和组织学类型与BMI升高无关。重要的是，肥胖女性的肿瘤比非肥胖患者的肿瘤表达的PTEN显著更少（P < 0.008），p27（kip1）也更少（P < 0.01）。PTEN和p27（kip1）表达均缺失的75例（32%）肿瘤具有良好的临床结局，尤其是在肥胖患者的FIGO I期和II期（P = 0.003）。Cox回归分析显示，PTEN/p27（kip1）表型、FIGO分期和组织学分级是子宫内膜样腺癌预后的独立预测因素。
PTEN/p27（kip1）蛋白失活是肥胖患者子宫内膜癌进展的一个特定特征。肥胖患者中PTEN/p27（kip1）蛋白表达联合缺失的表型与子宫内膜样腺癌显著更好的预后相关。
