中华肝脏病杂志
中華肝髒病雜誌
중화간장병잡지
CHINESE JOURNAL OF HEPATOLOGY
2013年
12期
924-928
,共5页
张勤%马喆%辛琪%刘贵秋%刘冰冰%高英堂%张传山%杜智
張勤%馬喆%辛琪%劉貴鞦%劉冰冰%高英堂%張傳山%杜智
장근%마철%신기%류귀추%류빙빙%고영당%장전산%두지
癌,肝细胞%诊断,鉴别%小胆管反应%间质浸润
癌,肝細胞%診斷,鑒彆%小膽管反應%間質浸潤
암,간세포%진단,감별%소담관반응%간질침윤
Carcinoma,hepatocellular%Diagnosis,differential%Ductular reaction%Stromal invasion
目的 探讨结节边缘小胆管反应(DR)缺失在鉴别具有乙型肝炎肝硬化背景的小肝癌中的作用.方法 对20份早期肝癌(直径≤3cm)、26份进展期肝癌(直径＞3cm)、20份高级别不典型增生结节(HGDNs)、26份低级别不典型增生结节(LGDNs)及20份因肝硬化脾大行肝活组织检查的肝硬化组织(约1cm×1cm)分别进行细胞角蛋白(CK)7和CK19免疫组织化学染色.观察两种蛋白在不同肝细胞性结节中的表达情况,并进行半定量分析.收集患者相关的临床资料.计数资料组间比较用配对x2检验及Fisher’s直接概率法检验;抗体与临床资料间的相关性用Parson相关分析;评判DR的诊断价值用Z检验;Kaplan-Meier生存曲线的比较用Logrank检验;计量资料的比较用独立样本t检验.结果 对112例患者随访41.59(3～ 90)个月.CK7及CK19在DR的肝胆管细胞胞质中阳性,此外在小叶间胆管及少部分肝细胞中也阳性.DR分布于肝细胞性结节周围,DR缺失或减少可以显示不明显的微浸润.DR/CK7和DR/CK19在LGDNs和肝硬化组织中DR均表现为强阳性,DR在大部分HGDNs中阳性表达,而在大部分早期肝癌及进展期肝癌中缺失.统计学分析显示:DR/CK19在早期肝癌中的缺失率高于HGDNs、LGDNs及肝硬化组(校正x2值分别为9.10,16.83,12.10,P值均＜0.01);DR/CK7的缺失率在早期肝癌中低于进展期肝癌(校正x2=5.17,P＜ 0.05),明显高于LGDNs及肝硬化组(校正x2值分别为8.05,10.24,P值均＜0.01).DR/CK7与DR/CK19的受试者工作特征曲线下面积很接近(Z=0.09,P＞0.05).Pearson相关分析结果显示,DR/CK7、DR/CK19与无瘤生存时间呈正相关(r=0.541,0.552,P值均＜0.01),与早期复发时间(r值分别为-0.387,-0.413,P值均＜0.01)及病死率(r值分别为-0.446,-0.507,P值均＜ 0.01)呈负相关.生存分析显示,DR的缺失可提示完全生存率和无瘤生存率明显降低(P＜0.01),发生早期复发的概率明显升高(P＜ 0.01).结论 DR/CK7、DR/CK19的缺失均可以显示早期肝癌的微浸润,因此可以用于鉴别早期肝癌与HGDNs;DR的缺失还提示预后不良.
目的 探討結節邊緣小膽管反應(DR)缺失在鑒彆具有乙型肝炎肝硬化揹景的小肝癌中的作用.方法 對20份早期肝癌(直徑≤3cm)、26份進展期肝癌(直徑＞3cm)、20份高級彆不典型增生結節(HGDNs)、26份低級彆不典型增生結節(LGDNs)及20份因肝硬化脾大行肝活組織檢查的肝硬化組織(約1cm×1cm)分彆進行細胞角蛋白(CK)7和CK19免疫組織化學染色.觀察兩種蛋白在不同肝細胞性結節中的錶達情況,併進行半定量分析.收集患者相關的臨床資料.計數資料組間比較用配對x2檢驗及Fisher’s直接概率法檢驗;抗體與臨床資料間的相關性用Parson相關分析;評判DR的診斷價值用Z檢驗;Kaplan-Meier生存麯線的比較用Logrank檢驗;計量資料的比較用獨立樣本t檢驗.結果 對112例患者隨訪41.59(3～ 90)箇月.CK7及CK19在DR的肝膽管細胞胞質中暘性,此外在小葉間膽管及少部分肝細胞中也暘性.DR分佈于肝細胞性結節週圍,DR缺失或減少可以顯示不明顯的微浸潤.DR/CK7和DR/CK19在LGDNs和肝硬化組織中DR均錶現為彊暘性,DR在大部分HGDNs中暘性錶達,而在大部分早期肝癌及進展期肝癌中缺失.統計學分析顯示:DR/CK19在早期肝癌中的缺失率高于HGDNs、LGDNs及肝硬化組(校正x2值分彆為9.10,16.83,12.10,P值均＜0.01);DR/CK7的缺失率在早期肝癌中低于進展期肝癌(校正x2=5.17,P＜ 0.05),明顯高于LGDNs及肝硬化組(校正x2值分彆為8.05,10.24,P值均＜0.01).DR/CK7與DR/CK19的受試者工作特徵麯線下麵積很接近(Z=0.09,P＞0.05).Pearson相關分析結果顯示,DR/CK7、DR/CK19與無瘤生存時間呈正相關(r=0.541,0.552,P值均＜0.01),與早期複髮時間(r值分彆為-0.387,-0.413,P值均＜0.01)及病死率(r值分彆為-0.446,-0.507,P值均＜ 0.01)呈負相關.生存分析顯示,DR的缺失可提示完全生存率和無瘤生存率明顯降低(P＜0.01),髮生早期複髮的概率明顯升高(P＜ 0.01).結論 DR/CK7、DR/CK19的缺失均可以顯示早期肝癌的微浸潤,因此可以用于鑒彆早期肝癌與HGDNs;DR的缺失還提示預後不良.
목적 탐토결절변연소담관반응(DR)결실재감별구유을형간염간경화배경적소간암중적작용.방법 대20빈조기간암(직경≤3cm)、26빈진전기간암(직경＞3cm)、20빈고급별불전형증생결절(HGDNs)、26빈저급별불전형증생결절(LGDNs)급20빈인간경화비대행간활조직검사적간경화조직(약1cm×1cm)분별진행세포각단백(CK)7화CK19면역조직화학염색.관찰량충단백재불동간세포성결절중적표체정황,병진행반정량분석.수집환자상관적림상자료.계수자료조간비교용배대x2검험급Fisher’s직접개솔법검험;항체여림상자료간적상관성용Parson상관분석;평판DR적진단개치용Z검험;Kaplan-Meier생존곡선적비교용Logrank검험;계량자료적비교용독립양본t검험.결과 대112례환자수방41.59(3～ 90)개월.CK7급CK19재DR적간담관세포포질중양성,차외재소협간담관급소부분간세포중야양성.DR분포우간세포성결절주위,DR결실혹감소가이현시불명현적미침윤.DR/CK7화DR/CK19재LGDNs화간경화조직중DR균표현위강양성,DR재대부분HGDNs중양성표체,이재대부분조기간암급진전기간암중결실.통계학분석현시:DR/CK19재조기간암중적결실솔고우HGDNs、LGDNs급간경화조(교정x2치분별위9.10,16.83,12.10,P치균＜0.01);DR/CK7적결실솔재조기간암중저우진전기간암(교정x2=5.17,P＜ 0.05),명현고우LGDNs급간경화조(교정x2치분별위8.05,10.24,P치균＜0.01).DR/CK7여DR/CK19적수시자공작특정곡선하면적흔접근(Z=0.09,P＞0.05).Pearson상관분석결과현시,DR/CK7、DR/CK19여무류생존시간정정상관(r=0.541,0.552,P치균＜0.01),여조기복발시간(r치분별위-0.387,-0.413,P치균＜0.01)급병사솔(r치분별위-0.446,-0.507,P치균＜ 0.01)정부상관.생존분석현시,DR적결실가제시완전생존솔화무류생존솔명현강저(P＜0.01),발생조기복발적개솔명현승고(P＜ 0.01).결론 DR/CK7、DR/CK19적결실균가이현시조기간암적미침윤,인차가이용우감별조기간암여HGDNs;DR적결실환제시예후불량.
Objective To investigate the role of absent ductular reaction (DR) at hepatocellularstromal boundaries in early stage hepatocellular carcinoma (HCC) with cirrhosis in patients with chronic hepatitis B.Methods Cytokeratin (CK)7 and CK19 expression was detected by the SP immunohistochemistry method in 112 hepatic nodules taken from 20 cases of early HCC,26 cases of HCC with nodules ＞ 3 cm,20 cases of high-grade dysplastic nodule (HGDN),26 cases of low-grade dysplastic nodule (LGDN),and 20 cases of cirrhosis (CIR).DR/CK7 and DR/CK19 were assessed separately on a semi-quantitative scale and statistically analyzed.Results The mean age of the patients in the study was 53.71 years-old,and the study population consisted of 73 males and 39 females.The followup time ranged from 3 to 90 months.Positive CK7 and CK19 staining was detected in the cytoplasm of DRpositive hepatobiliary cells,inteflobular bile duct,and a portion of hepatic cells.All of the DR/CK7-and DR/CK19-positive cells were localized around the non-invasive nodules.Specimens with focal or diffuse DR/CK7-and DR/CK19-1oss had more robust stromal invasion.Specimens from early HCC cases showed greater DR/CK19 loss than specimens from HGDN cases,LGDN cases and CIR cases (all P ＜ 0.01).DR/CK7 loss of early HCC was less than HCC with nodules ＞ 3 cm (P ＜ 0.05),and more than LGDN cases and CIR cases Cboth P ＜ 0.01).The area under the receiver operating characteristic curve of DR/CK7 was very similar to that of DR/CK19 (P ＞ 0.05).Pearson's correlation analysis indicated that DR/CK7 and DR/CK19 were positively correlated with tumor-free time (P ＜ 0.01) and negatively correlated with early recurrence time as well as death rate (bothP ＜ 0.01).Furthermore,cases showing DR/CK7 or DR/CK19 loss had lower overall survival rate and tumor-free survival rate (P ＜ 0.01) and higher early recurrence rate (P ＜ 0.01).Conclusion DR/CK7 and DR/CK19 immunostaining may help to distinguish non-invasive HGDNs from both minimally-invasive and overtly-invasive HCCs by identifying small foci of invasion and predicting increased risk of invasiveness.
