【作者】 刘迪填；

【导师】 杨捷生；

【作者基本信息】 汕头大学 ， 上消化道肿瘤的外科治疗， 2002， 硕士

【摘要】 在我国贲门癌为一高发的恶性肿瘤，死亡率高。目前主要的治疗方法是手术治疗，但预后仍未令人满意。术后死亡主要原因是肿瘤复发和转移。因此除应用临床资料作为治疗选择的依据外，找到预后的预测因子，准确判断其预后，发现有明显恶性倾向的患者，并及时进行术后的综合治疗显得至关重要。WAF1和C-erbB-2是近年发现的与细胞增殖有密切关系的基因，据报道它们的表达与多种肿瘤的临床意义有关。本研究的目的是：1检测贲门癌中WAF1和C-erbB-2基因蛋白的表达；2分析其表达与临床病理参数之间的关系；3结合临床资料了解WAF1和C-erbB-2基因蛋白表达的预后价值。 材料和方法：选择1994-1995年在汕头大学医学院附属肿瘤医院胸科行手术治疗并经病理确诊而且于汕头大学医学院病理科保存完好的贲门癌蜡块104例。应用免疫组化二步法检测104例贲门癌组织中WAF1和C-erbB-2基因蛋白表达的状况，结合临床病理资料进行分析。 结果： 贲门癌组织中WAF1基因蛋白表达主要定位于细胞核，少数定位于细胞核的顶端，其癌组织的阳性率为26.0％(27／104)。而贲门癌组织中C-erbB-2基因蛋白表达的主要定位于细胞浆及细胞膜，其癌组织的阳性率为55.8％(58／104)，其中弱阳性率为20.2％(21／104)，强阳性率为35.6％(37／104)。WAF1基因蛋白的表达与肿瘤的大小、分化程度、淋巴结转移及外侵密切相关。大体最大径＜5cm组WAF1基因蛋白的表达率高于大体最大径≥5cm组(55.6％ vs 19.8％ P=0.004)。高中分化组WAF1基因蛋白的表达率高于低分化组(40.6％vs 19.1％ P=0.037)。淋巴结转移组WAF1基因蛋白的表达率低于淋 巴结无转移组Q0．3％VS 40．0％P＝0 03o。局部肿瘤无外侵组 WAFI 基因蛋白的表达率明显高于外侵组o 5．5％V Sll．9％P＝0 00O。而 且WAFI基因蛋白的表达率与不同的PTNM分期有关。I｛、Ill、IV 期的 WAFI 基因蛋白的表达阳性率分别为 43．5％、30．2％、 3．6叭 P＝0 003。C飞rbB七基因蛋白过表达与肿瘤的分化程度、淋i 巴结转移及临床 PTNM分期密切相关。淋巴结转移组 C飞rbB七蛋白表 达强阳性率高于淋巴结无转移组N3．2％VS 16．7％尸司．010人高分 化组、中分化组及低分化组C飞rbB上蛋白表达强阳性率分别为62．5％ （10／16）、43．8％（7／16）及 31．97（15／47）。中低 分化组 C－erbB－2 蛋白表达强阳性率低于高分化组（P刀．045人 IH 期组 C飞rbB七蛋 白表达强阳性率低于 Ill＋IV期组门．4％VS 40．7％尸＝0．039）。结 合随访资料分析表明WAF、C飞rbB上基因蛋白的表达与预后有关。 WAF表达阳性组1、3、5年的生存率分别为SS．2＊、38．87、26．6y， 而 WAFI 表达阴性组 1、3、5年的生存率分别为 66．47、32．6％、22．4％ （P＜0．05人 C飞rbB七基因蛋白表达阴性及弱阳性组 1、3、5年 的生存率分别为S3．2％、35．5％、24．5％，而C－erbB－2基因蛋白表达 强阳性组 1、3、5年的生存率分别为 50．0％、31．7％、ZI．4％（尸＜ 0．05）。 本组结果还显示：贲门癌组织中WAFI基因蛋白表达与C飞rbB《基因 蛋白强阳性表达无关。WAF及C飞rbB七基因蛋白表达与年龄／性别。 大体类型、组织类型、手术性质、浆膜是否受累及食管是否受累均无 关。C飞rbB六基因蛋白的表达与肿瘤大小、肿瘤浸润深度也无关。 结论： 1．贡门癌组织中WAFI基因蛋白表达与肿瘤的大小、分化程度、淋巴 结转移、局部外侵、PTN’M分期和预后有关。贲门癌组织中 WAFI基 因蛋白的表达缺失与病变的进展相关，WAFI基因蛋白表达者预后好， 表达缺失者预后差。 2．C《rbB上基因蛋白表达与贲门癌的分化程度、淋巴结转移、PTNM 分期和预后有关，C七rbB上基因蛋白的强阳性表达者与病变的进展及 预后差相关。．3．认为通过免疫组化法检测 WAFI及 C七rbB2基因蛋白在贲门癌组 织中的表达可能有助预测贲门癌患者的预后。更多还原

【Abstract】 Cardiac carcinoma is a commonly seen malignant cancer in our country with a high mortality. So far, the major management for it is treated surgically. However, the therapeutic effect is far from as satisfied as expected. The main causes of death following operation were the recurrence and metastasis of the disease. So in addition to making use of the clinical data as the evidences of choice for treatment, how to find out the prognostic predictors, precisely assess the prognosis and identify the patients with more malignant potential and then perform combined therapy for those patients in time are becoming very crucial. The genes of WAF1 and C-erbB-2 discovered recently, whose expressions status were reported to be clinically valuable in various rumors, were closely associated with cell proliferation.THE OBJECTIVES:l.to investigate the expressions of WAF1 and C-erbB-2 oncogene protein in cardiac carcinoma;2. to evaluate the relationship between the expressions of WAF1 and C-erbB-2 oncogene protein and the clinicopathological factors in cardiac carcinoma;3. to assess the prognostic significance of the expressions of WAF1 and C-erbB-2 oncogene protein in cardiac carcinoma.MATERAL and METHODS:In the current study, one hundred and four cases of cardiac carcinoma wereselected from patients who had undergone operation in the Department of Thoracic Surgery, Affiliated Tumor Hospital Medical School of Shantou University in the period of from 1994 to 1995. The diagnosis of all the selected cases had been confirmed through pathological examination and their blocks were embeded in paraffin and preserved well in the Department of Pathology, Medical School of Shantou University. The expressions of WAF1 and C-erbB-2 oncogene protein in 104 cardiac carcinoma samples were detected by immunohistochemical Two-step method and a retrospective analysis was performed combined with data of clinicopathology. RESULTS:The majority of WAF1 protein staining was noted in cellular nucleus and some on the top of nucleus with a positive rate of 26.0%(27/104). In contrast, a great number of C-erbB-2 oncogene protein staining was found to be located in cytoplasm and cytomembrane with a positive rate of 55.8%(37/104), including a weak positive rate of 20.2%(21/104), and a strong positve rate of 35.6%(37/104). The positive expression of WAF1 oncogene protein was significantly correlation with the maximal gross dimension, the degree of differentiation, lymph node metastasis, external invasion and PTNM staging in cardiac carcinoma. The expression of WAF1 oncogene protein in the group with the maximal gross dimension <5cm was higher than that of the group with the maximal gross dimension^5cm (55.6% vs 19.8% P=0.004 ). The expression rate of WAF1 oncogene protein in the group of well and moderate-differentiated tumors were higher than that of the poor-differentiated ones (40.6% vs 19.1% P=0.037 ). In the group with lymph node metastasis, the expression of WAF1 protein was lower than that of those without lymph node involvement (20.3% vs 40.6% P=0.037). The expression rate of WAF 1 oncogene protein in the group of without invasion to adjacent organ was higher than that of those with adjoining involvement (35.5% vs 11.9% P=0.007 ). Furthermore, the current results demonstrated the expression of WAF 1 oncogene protein was closely related to PTNM staging. The expression rate of WAF 1 oncogene protein in the group of I-IL UK IV staging were 43.5%, 30.2% and 3.6% respectively, whose difference was greatly significant according tostatistical analysis(P=0.003). Overexpression of C-erbB-2 protein was significantly correlated with differentiation of tumor, lymph node metastasis and PTNM staging. The strong positive rate of C-erbB-2 protein in the group of lymph node metastasis was higher than that of those with no lymph node metastasis (43.2% vs 16.7% P=0.01)). The strong expression rates of C-erbB-2 oncogene protein in the well-differentiated tumors, moderate-differentiated tumors and poor-differentiated tumors were 62.5%(10/16)更多还原