CAJ | 학술논문

目的探讨磷脂酰肌醇3激酶/蛋白激酶( PI3 K/AKT)信号通路的重要组分PTEN、PIK3CA和p-AKT在子宫内膜癌组织中的改变及其预后意义.方法免疫组织化学EnVision二步法检测PTEN、p-AKT、雌激素受体(ER)和孕激素受体在71例子宫内膜癌组织中的表达,聚合酶链反应测序法分析其中34例PIK3CA基因外显子9和20的突变情况.结果 (1)71例子宫内膜癌组织中,子宫内膜样癌( EEC) 65例,非子宫内膜样癌(NEEC)6例.PTEN失表达率为63.4％( 45/71),在EEC中的比例(66.2％,43/65)高于NEEC( 2/6；P=0.18).PTEN失表达患者(45例)预后优于PTEN正常表达者(26例；P=0.07).进一步分组分析显示在ER阴性病例中,PTEN失表达者(12例)的预后优于PTEN正常表达者(7例),差异有统计学意义(P=0.04).(2)本组34例中PIK3CA突变率为41.2％ (14/34),突变热点为外显子9的T544.PIK3CA突变在EEC中的发生比例(44.8％,13/29)高于NEEC( 1/5；P ＞0.05).外显子9突变全部见于Ⅰ期EEC病例中,且在高、中分化的EEC中发生率高于低分化肿瘤(P＞0.05).外显子20突变在早期病例组(14.3％,4/28)的发生率显著低于晚期病例组(4/6；P=0.0l).(3)p-AKT的阳性率为59.2％ (42/71),在EEC中的阳性率(60.0％,39/65)高于NEEC(3/6；P=0.68)；但高、中分化组EEC的阳性比例(75.0％,21/28；53.6％,15/28)高于低分化组(3/9),差异有统计学意义(P=0.02).p-AKT阳性与ER阳性相关(r=0.339,P=0.00).结论 PI3K/AKT信号通路的关键分子,如PTEN失表达、p-AKT阳性提示预后好.PIK3CA基因外显子9和20的突变对子宫内膜癌的预后影响可能不同.子宫内膜癌中PTEN和p-AKT的功能可能受到ER状态的影响.
목적 탐토린지선기순3격매/단백격매( PI3 K/AKT)신호통로적중요조분PTEN、PIK3CA화p-AKT재자궁내막암조직중적개변급기예후의의.방법 면역조직화학EnVision이보법검측PTEN、p-AKT、자격소수체(ER)화잉격소수체재71례자궁내막암조직중적표체,취합매련반응측서법분석기중34례PIK3CA기인외현자9화20적돌변정황.결과 (1)71례자궁내막암조직중,자궁내막양암( EEC) 65례,비자궁내막양암(NEEC)6례.PTEN실표체솔위63.4％( 45/71),재EEC중적비례(66.2％,43/65)고우NEEC( 2/6；P=0.18).PTEN실표체환자(45례)예후우우PTEN정상표체자(26례；P=0.07).진일보분조분석현시재ER음성병례중,PTEN실표체자(12례)적예후우우PTEN정상표체자(7례),차이유통계학의의(P=0.04).(2)본조34례중PIK3CA돌변솔위41.2％ (14/34),돌변열점위외현자9적T544.PIK3CA돌변재EEC중적발생비례(44.8％,13/29)고우NEEC( 1/5；P ＞0.05).외현자9돌변전부견우Ⅰ기EEC병례중,차재고、중분화적EEC중발생솔고우저분화종류(P＞0.05).외현자20돌변재조기병례조(14.3％,4/28)적발생솔현저저우만기병례조(4/6；P=0.0l).(3)p-AKT적양성솔위59.2％ (42/71),재EEC중적양성솔(60.0％,39/65)고우NEEC(3/6；P=0.68)；단고、중분화조EEC적양성비례(75.0％,21/28；53.6％,15/28)고우저분화조(3/9),차이유통계학의의(P=0.02).p-AKT양성여ER양성상관(r=0.339,P=0.00).결론 PI3K/AKT신호통로적관건분자,여PTEN실표체、p-AKT양성제시예후호.PIK3CA기인외현자9화20적돌변대자궁내막암적예후영향가능불동.자궁내막암중PTEN화p-AKT적공능가능수도ER상태적영향.
Objective To investigate the clinicopathologic and prognostic implications of phosphoinositide 3 kinase (PI3K)/AKT pathway alterations in endometrial cancers of Chinese women.Methods The expression of PTEN,p-AKT,and ER/PR was assessed in 71 cases of endometrial carcinoma by immunohistochemistry (EnVision method).The PIK3CA mutation at exon 9 and exon 20 was analyzed by PCR and direct sequencing in 34 tumors.Results ( 1 ) Of the 71 cases of endometrial carcinoma,65 cases were endometrioid adenocarcinoma (EEC) and 6 cases were nonendometrioid adenocarcinoma (NEEC).PTEN loss of expression was found in 63.4％ (45/71)of tumors,and more commonly occurred in EEC (66.2％,43/65) than that in NEEC (2/6,P=0.18).Patients with PTEN loss in their tumors (45 cases) had a better survival than those without (26 cases,P =0.07).In ER negative subgroup,the patients with PTEN loss of expression ( 12 cases ) had longer survival than those with normal PTEN expression (7 cases; P =0.04).(2) The frequency of PIK3CA mutation was 41.2％ (14/34) with a hot mutation spot at T544 in exon 9.PIK3CA mutations more commonly occurred in EEC (44.8％,13/29)than in NEEC ( 1/5,P ＞ 0.05 ).The mutations at exon 9 more commonly occurred in EEC,well- and moderately-differentiated EEC,and tumors at early stage ( P ＞ 0.05 ).On the contrary,in tumors at early stages,the frequency of mutations in exon 20( 14.3％,4/28 )was significantly lower than that at late stages (4/6,P =0.01 ).(3) p-AKT was positive in 59.2％ (42/71) of tumors that were more frequently found in EEC (60.0％,39/65 ) than that in NEEC ( 3/6,P =0.68 ).However,the significant difference of p-AKT expression was found between well- and moderately-differentiated EEC (75.0％,21/28; 53.6％,15/28) and poorly-differentiated EEC ( 3/9,P =0.02 ).Moreover,p-AKT expression was significantly correlated with positive ER ( r =0.339,P =0.00).Conclusions Endometrial carcinoma patients with loss of PTEN and p-AKT positivity have a favorable prognosis.PIK3CA mutations at exon 9 or 20 may have different impact on the prognosis.The function of PTEN loss and p-AKT expression may vary according to different hormone status.