上皮细胞黏附分子和β-环连蛋白在上皮性卵巢癌组织中的表达及其在预后评估中的作用
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摘要
目的:卵巢癌是女性生殖系统常见的恶性肿瘤之一,发病率仅次于子宫颈癌和子宫体癌而列居第三位。卵巢恶性肿瘤组织学分类包括上皮性肿瘤,生殖细胞肿瘤,性索间质肿瘤,脂质细胞瘤,性腺母细胞瘤,非卵巢特异性软组织肿瘤,未分类肿瘤,转移性肿瘤,瘤样病变。其中上皮性肿瘤占卵巢恶性肿瘤的85%～90%。其发病年龄在50～60岁,由于卵巢的胚胎发育,组织解剖及内分泌功能较复杂,且卵巢癌临床早期无症状,早期诊断及鉴别其组织类型和良、恶性相当困难,卵巢癌行剖腹探查术中发现肿瘤局限于卵巢的仅占30%,大多数已扩散到子宫,双侧附件,大网膜及盆腔各器官,确诊时60%～70%已属中晚期。上皮性卵巢癌(epithelial ovarian cancer, EOC)的治疗效果一直未能改善,五年生存率徘徊于30%～40%,死亡率居于妇科恶性肿瘤首位。卵巢恶性上皮性肿瘤已成为严重威胁妇女生命和健康的主要肿瘤[1]。大多数病人由于上腹部疾病,胸腔疾病及发现淋巴结肿大而收入院诊断为卵巢癌。尽管卵巢癌具有高度致死性,但其临床过程很难被评估。外科常规手术预后的评估大多基于临床的组织病理特征,例如:FIGO分期,肿瘤组织学分期,组织学类型,年龄及术后残留肿物大小来评价[2]。了解上皮性卵巢癌预后因素能协助其个体化治疗,从而改善长期生存[3]。近期很多学者在这方面进行了研究并且提供了更多的预后指标。目前临床及生物学领域都无法为上皮性卵巢癌病人提供充分的预后评估以及可以作为依据的评估标准。本试验旨在为上皮性卵巢癌提供潜在生物学指标对其进行预后评估。通过回顾性研究观察上皮细胞黏附分子(epithelial celladhesion molecule,EP-CAM)、β-环连蛋白(β-catenin)在上皮性卵巢组织中的表达,以寻找其对上皮性卵巢癌预后评估的价值。
方法:运用免疫组织化学技术(S-P法)检测EP-CAM和β-catenin在20例正常卵巢组织、20例卵巢良性肿瘤和43例EOC组织中的表达。同时对以上病人随访其生存率。
结果:EP-CAM在卵巢恶性肿瘤组织中的表达为79%,在卵巢良性肿瘤上皮中的表达为65%,在正常卵巢组织中的表达为40%。差异有统计学意义(P<0. 05)。在EP-CAM表达组中,其在正常卵巢组织及卵巢良性组织中的过表达均为0,在恶性肿瘤组织中表达率为56%,差异有统计学意义(P=0. 001)。在EP-CAM阳性表达与不表达、弱阳性表达与过表达患者预后生存时间比较的同一性检验中,差异均有统计学意义,后者差异更显著。由此可见,EP-CAM的过表达与卵巢癌的不良预后呈正相关。β-catenin在43例卵巢癌组织中其正常呈棕黄色细胞膜表达9例(21%),异常表达(包括β-catenin的表达消失或在胞浆和/或胞核中出现异常积聚)共34例(79%),其中表达缺失14例(33%),异位表达6例(14%),异质性表达14例(33%)。其正常表达组与异常表达组患者预后生存时间比较的同一性检验中差异有统计学意义,Ⅲ-Ⅳ组较Ⅰ-Ⅱ期差异更显著。
结论:本研究表明①EP-CAM的表达从正常卵巢上皮到良性卵巢肿瘤上皮再到EOC逐渐增高,其过表达仅在EOC出现,提示EP-CAM可能参与上皮性卵巢癌的恶变过程。②EP-CAM在Ⅲ-Ⅳ期上皮性卵巢癌组织中的过表达率较Ⅰ-Ⅱ期明显升高,提示组织中EP-CAM过表达患者可能是上皮性卵巢癌晚期。>60岁年龄组较≤60岁年龄组EP-CAM的过表达率增高。③EOC组织EP-CAM表达评分增加和β-catenin异常表达患者生存时间有下降趋势,提示EP-CAM和β-catenin在卵巢癌组织中的异常表达对卵巢癌预后评估有指导作用。
Objective: Ovarian cancer is one of the most frequently seen malignancies in female, the incidence is third followed cervical cancer and endometrial carcinoma. The inhistology typings of ovarial malignancy are include: epithelial tumour, germ celcancer, sexcord-stromaltumor, lipidcell tumor, Gonadoblastoma, non-ovarial specificity soft connective tissue tumor, not elsewhere classifiable tumor, metastatic tumor, tumor-like lesion. Almost 85%~90% of primary ovarian tumor derive from epithelial cells. Most ovarian cancer are diagnosed among the ages of 50~60. Because of the multiplicity of the embryonic development, the dissect of the tissue and endocrine fuction, ovarian cancer is absence of symptoms in earlier period. So it is difficult to discriminate the type and property of ovarian cancer. In the exploratory laparotomy of ovarian cancer we can find the tumors located in ovaries only are 30%, mostly have been diffused to uterus, ambi-accompaniment, colicomentum and other organ in cavitas pelvis. To final diagnosis, about 60~70% ovarian cancer are in middle and advanced stage. The therapeutic efficacy of epithelial ovarial cancer are fail amelioration, five year surivival rate are 30~40%, death rate is first place in department of gynecology malignant tumor. Epithelial ovarial cancer have been chief tumor which serious threaten female’s life and health[1]. Most patients of ovarian cancer were in hospital on account of celiac disease, cavitas thoracis disease and lymphadenectasis. Although ovarian cancer is high-fatal, the clinical course is difficult to be valuation. Prognostic predictors are currently based on clinical and histopathological features including: FIGO stage, histologic grade of tumor, histologic subtype, age at diagnosis, and residual tumor after surgical treatment[2]. To know the prognosis factor of EOC can help the individualized treatment and improve long term survival. Recently a great of scolars study in this aspect provid a lot of prognosis marker. Currently available clinical and molecular factors provide still an insufficient prognostic and predictive assessment for patients with epithelial ovarian cancer (EOC). To identify a potential molecular target and prognostic/predictive factor for EOC, we investigated in a retrospective study the prognostic value of Ep-CAM、β- catenin expression in EOC.
Methods: The expression of EP-CAM was detected with immunohistochemical stain in 20 cases of normal ovarian epithelium, 20 cases of ovarian benign epithelial tumor and 43 cases of epithelial ovarian cancer. The expression ofβ-catenin was detected with immunohistochemical stain in 43 cases of epithelial ovarian cancer.
Results: The expression rates of EP-CAM were 79%, 65%, 40% for epithelial ovarian cancer, ovarian benign epithelial tumor, and normal ovarian epithelial groups. The difference has statistical significance(P<0.05).The EP-CAM over- expression rates in normal ovarian epithelial and ovarian benign epithelial tumor groups were zero. But the expression rate was 56% in epithelial ovarian cancer group(P=0. 001). The contrast has statistical significance. Compared the expression with absence expression of EP-CAM and the low expression with overexpression of EP-CAM, the results of the live time of patients in identity test all were significance. The latter was more patency. So the overexpression of EP-CAM was positive correlated with the dys-prognostic of epithelial ovarian cancer. In 43 cases ovarian cancer tissues, the expression ofβ-catenin were 9 (21%)cases normal expression(cellular membrane expression with brown), 34 (79%) cases abnormal expression(no expression, cytoplasmic or/and nuclear expressions). Among the abnormal expression tissues, absence expressions were 14(33%) cases, ectopic expressions were 6(14%) cases, heterogeneity expressions were 14(33%) cases. Compared normal expression group with the abnormal expression group, the result of the live time of patients in identity test was significance. TheⅢ-Ⅳgroup was more significance thanⅠ-Ⅱgroup. So the abnormal expression ofβ-catenin in the ovarian cancer was contribute with the evaluate of prognostic in epithelial ovarian cancer.
Conclusion 1. The rates of expression of EP-CAM increased from normal ovarian tissue, ovarian benign epithelial tumor and epithelial ovarian cancer. The overexpression of EP-CAM appearance only in EOC. So the result in this study suggested that the expression of EP-CAM involved in the carcinogenesis of EOC. 2. In 43 cases EOC, the rate of overexpression of EP-CAM inⅢ-Ⅳgroup was obviously higher thanⅠ-Ⅱgroup. The difference was significance. Compared with different age groups, the expression rates of EP-CAM were higher in the group >60 than the group≤60. The difference has statistical significance. 3. With the increasing of the score of the expression of EP-CAM, the live time of patients were degression. 4. With the abnormal expression ofβ-catenin, the live time of patients were degression.
方法:运用免疫组织化学技术(S-P法)检测EP-CAM和β-catenin在20例正常卵巢组织、20例卵巢良性肿瘤和43例EOC组织中的表达。同时对以上病人随访其生存率。
结果:EP-CAM在卵巢恶性肿瘤组织中的表达为79%,在卵巢良性肿瘤上皮中的表达为65%,在正常卵巢组织中的表达为40%。差异有统计学意义(P<0. 05)。在EP-CAM表达组中,其在正常卵巢组织及卵巢良性组织中的过表达均为0,在恶性肿瘤组织中表达率为56%,差异有统计学意义(P=0. 001)。在EP-CAM阳性表达与不表达、弱阳性表达与过表达患者预后生存时间比较的同一性检验中,差异均有统计学意义,后者差异更显著。由此可见,EP-CAM的过表达与卵巢癌的不良预后呈正相关。β-catenin在43例卵巢癌组织中其正常呈棕黄色细胞膜表达9例(21%),异常表达(包括β-catenin的表达消失或在胞浆和/或胞核中出现异常积聚)共34例(79%),其中表达缺失14例(33%),异位表达6例(14%),异质性表达14例(33%)。其正常表达组与异常表达组患者预后生存时间比较的同一性检验中差异有统计学意义,Ⅲ-Ⅳ组较Ⅰ-Ⅱ期差异更显著。
结论:本研究表明①EP-CAM的表达从正常卵巢上皮到良性卵巢肿瘤上皮再到EOC逐渐增高,其过表达仅在EOC出现,提示EP-CAM可能参与上皮性卵巢癌的恶变过程。②EP-CAM在Ⅲ-Ⅳ期上皮性卵巢癌组织中的过表达率较Ⅰ-Ⅱ期明显升高,提示组织中EP-CAM过表达患者可能是上皮性卵巢癌晚期。>60岁年龄组较≤60岁年龄组EP-CAM的过表达率增高。③EOC组织EP-CAM表达评分增加和β-catenin异常表达患者生存时间有下降趋势,提示EP-CAM和β-catenin在卵巢癌组织中的异常表达对卵巢癌预后评估有指导作用。
Objective: Ovarian cancer is one of the most frequently seen malignancies in female, the incidence is third followed cervical cancer and endometrial carcinoma. The inhistology typings of ovarial malignancy are include: epithelial tumour, germ celcancer, sexcord-stromaltumor, lipidcell tumor, Gonadoblastoma, non-ovarial specificity soft connective tissue tumor, not elsewhere classifiable tumor, metastatic tumor, tumor-like lesion. Almost 85%~90% of primary ovarian tumor derive from epithelial cells. Most ovarian cancer are diagnosed among the ages of 50~60. Because of the multiplicity of the embryonic development, the dissect of the tissue and endocrine fuction, ovarian cancer is absence of symptoms in earlier period. So it is difficult to discriminate the type and property of ovarian cancer. In the exploratory laparotomy of ovarian cancer we can find the tumors located in ovaries only are 30%, mostly have been diffused to uterus, ambi-accompaniment, colicomentum and other organ in cavitas pelvis. To final diagnosis, about 60~70% ovarian cancer are in middle and advanced stage. The therapeutic efficacy of epithelial ovarial cancer are fail amelioration, five year surivival rate are 30~40%, death rate is first place in department of gynecology malignant tumor. Epithelial ovarial cancer have been chief tumor which serious threaten female’s life and health[1]. Most patients of ovarian cancer were in hospital on account of celiac disease, cavitas thoracis disease and lymphadenectasis. Although ovarian cancer is high-fatal, the clinical course is difficult to be valuation. Prognostic predictors are currently based on clinical and histopathological features including: FIGO stage, histologic grade of tumor, histologic subtype, age at diagnosis, and residual tumor after surgical treatment[2]. To know the prognosis factor of EOC can help the individualized treatment and improve long term survival. Recently a great of scolars study in this aspect provid a lot of prognosis marker. Currently available clinical and molecular factors provide still an insufficient prognostic and predictive assessment for patients with epithelial ovarian cancer (EOC). To identify a potential molecular target and prognostic/predictive factor for EOC, we investigated in a retrospective study the prognostic value of Ep-CAM、β- catenin expression in EOC.
Methods: The expression of EP-CAM was detected with immunohistochemical stain in 20 cases of normal ovarian epithelium, 20 cases of ovarian benign epithelial tumor and 43 cases of epithelial ovarian cancer. The expression ofβ-catenin was detected with immunohistochemical stain in 43 cases of epithelial ovarian cancer.
Results: The expression rates of EP-CAM were 79%, 65%, 40% for epithelial ovarian cancer, ovarian benign epithelial tumor, and normal ovarian epithelial groups. The difference has statistical significance(P<0.05).The EP-CAM over- expression rates in normal ovarian epithelial and ovarian benign epithelial tumor groups were zero. But the expression rate was 56% in epithelial ovarian cancer group(P=0. 001). The contrast has statistical significance. Compared the expression with absence expression of EP-CAM and the low expression with overexpression of EP-CAM, the results of the live time of patients in identity test all were significance. The latter was more patency. So the overexpression of EP-CAM was positive correlated with the dys-prognostic of epithelial ovarian cancer. In 43 cases ovarian cancer tissues, the expression ofβ-catenin were 9 (21%)cases normal expression(cellular membrane expression with brown), 34 (79%) cases abnormal expression(no expression, cytoplasmic or/and nuclear expressions). Among the abnormal expression tissues, absence expressions were 14(33%) cases, ectopic expressions were 6(14%) cases, heterogeneity expressions were 14(33%) cases. Compared normal expression group with the abnormal expression group, the result of the live time of patients in identity test was significance. TheⅢ-Ⅳgroup was more significance thanⅠ-Ⅱgroup. So the abnormal expression ofβ-catenin in the ovarian cancer was contribute with the evaluate of prognostic in epithelial ovarian cancer.
Conclusion 1. The rates of expression of EP-CAM increased from normal ovarian tissue, ovarian benign epithelial tumor and epithelial ovarian cancer. The overexpression of EP-CAM appearance only in EOC. So the result in this study suggested that the expression of EP-CAM involved in the carcinogenesis of EOC. 2. In 43 cases EOC, the rate of overexpression of EP-CAM inⅢ-Ⅳgroup was obviously higher thanⅠ-Ⅱgroup. The difference was significance. Compared with different age groups, the expression rates of EP-CAM were higher in the group >60 than the group≤60. The difference has statistical significance. 3. With the increasing of the score of the expression of EP-CAM, the live time of patients were degression. 4. With the abnormal expression ofβ-catenin, the live time of patients were degression.
引文
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