子宫内膜浆液性乳头状癌组织中Her-2/neu基因的扩增和蛋白表达及其意义

目的 检测Her-2/neu基因在子宫内膜浆液性乳头状癌(UPSC)中的扩增和蛋白表达情况,并分析其临床意义.方法 回顾性分析1996年1月-2006年1月在复旦大学附属肿瘤医院手术治疗的36例UPSC患者的临床病理资料,分别用显色原位杂交和免疫组化法检测Her-2/neu基因在UPS组织中的扩增和蛋白表达情况,并对两种方法进行对比分析;采用单因素log-rank检验、多因素Cox同归法分析影响UPSC预后的因素.同时随机选择同期收治、临床资料完整的136例Ⅰ型子宫内膜样腺癌作为对照,行免疫组化法检测其Her-2/neu蛋白的表达.结果 免疫组化法检测显示,UPSC患者Her-2/neu蛋白阳性表达率为36.1%(13/36), Ⅰ型子宫内膜样腺癌患者为6.6%(9/136),两者比较,差异有统计学意义(P=0.000).显色原位杂交法检测显示,UPSC患者Her-2/neu基因高度扩增率为11.1%(4/36).显色原位杂交和免疫组化法检测的符合率为100%.36例UPSC患者中,手术病理分期Ⅲ～Ⅳ患者的Her-2/neu蛋白阳性表达率为50.0%(11/22),明显高于Ⅰ～Ⅱ期患者的14.3%(2/14,P=0.030);而不同肌层浸润深度、病理类型构成、病理分化程度及有无脉管侵犯、p53蛋白、雌激素受体(ER)、孕激素受体(PR)表达患者间Her-2/neu蛋白阳性表达率比较,差异均无统计学意义(P>0.05).单因素分析显示,Her-2/neu蛋白表达、肌层浸润深度和手术病理分期是影响UPSC患者预后的危险因素(P<0.05);多因素分析显示,Her-2/neu蛋白表达和肌层浸润深度是影响UPSC患者预后的独立危险因素(P<0.05).Her-2/neu蛋白阳性表达的13例患者中,8例子化疗者平均牛存时间(20个月)较5例未化疗者(42个月)短,但差异无统计学意义(P=O.370).结论 UPSC组织中Her-2/neu蛋白阳性表达与手术分期晚显著相关,Her-2/neu蛋白表达和肌层浸润深度是影响UPSC预后的独立危险因素.     

子宫内膜癌组织中基因及分子标志物表达及其与预后的相关性研究

目的探讨子宫内膜癌组织中雌激素受体(ER)、孕激素受体(PR)、p53抑癌基因(p53)、抗原Ki-67(Ki-67)的表达及与临床预后之间的关系。方法选取2009—2014年广州医科大学附属第一医院妇科收治的79例子宫内膜癌患者的癌组织标本,采用免疫组化法检测其中ER、PR、p53、Ki-67的蛋白表达情况。结果 79例子宫内膜癌病例中,ER、PR、p53、Ki-67阳性表达率:87.3%、88.6%、84.8%、79.7%;ER的蛋白表达与患者预后有关;PR与病理类型、肌层浸润、组织分化有关;p53与组织分化有关;Ki-67与临床分期、淋巴转移有关(均P0.05)。ER与PR的表达、p53与Ki-67的表达均呈正相关(P0.05)。结论 ER、PR、p53、Ki-67的联合检测可能作为子宫内膜癌发生、发展及临床转移的生物学指标及作为判断子宫内膜癌恶性程度及评估预后的分子标志物,其具体作用机制值得进一步研究。     

分析p16、p53及Ki-67在宫颈癌患者中的表达及联合检测的诊断价值

目的 探讨p16、p53及Ki-67在宫颈癌患者中的表达意义及三项指标联合检测的诊断效能。方法 选取2019年6月至2022年10月在桂林医学院附属医院就医并确诊为宫颈癌的140例患者纳入宫颈癌组,另选取60例经本院确诊的高级别鳞状上皮病变患者纳入宫颈上皮内病变组,均为CIN2。收集本研究纳入患者的病理组织标本并检测p16、p53及Ki-67阳性表达情况,明确p16、p53及Ki-67与宫颈癌患者病理特征的关系,分析p16、p53及Ki-67三项指标联合检测对宫颈癌的诊断价值。结果 宫颈癌组病理组织标本中p16、p53及Ki-67阳性表达率均明显高于宫颈上皮内病变组（均P <0.05）;宫颈癌组中不同年龄患者的p16、p53及Ki-67阳性表达对比差异均无统计学意义（P>0.05）,不同FIGO分期及淋巴结转移患者p16、p53及Ki-67阳性表达明显升高（均P <0.05）;p16、p53、Ki-67三项联合的诊断效能包括灵敏度、特异度、阳性预测值、阴性预测值均明显高于单一指标的检测效能。结论 宫颈癌组织中p16、p53、Ki-67蛋白的阳性表达与宫颈癌患者病情的发...     

EZH2和Ki-67在宫颈癌组织中的表达及其临床意义

目的探讨EZH2和Ki-67在宫颈癌组织中的表达及其临床意义。方法采用免疫组化法分别检测40例正常宫颈、62例宫颈上皮内瘤变(CIN)及174例宫颈癌组织中EZH2和Ki-67蛋白的表达,并分析EZH2和Ki-67与临床病理特征及预后的关系。结果宫颈癌组和CIN组中EZH2和Ki-67蛋白的阳性表达率明显高于对照组,且宫颈癌组中EZH2和Ki-67蛋白的阳性表达率明显高于CIN组。在宫颈癌组织中,EZH2和Ki-67与临床分期、淋巴结转移及浸润深度密切相关(P0.05),且EZH2蛋白与病理分级有关(P0.05)。在随访的166例宫颈癌患者中,EZH2和Ki-67蛋白阳性表达患者的无进展生存时间(PFS)和总生存时间(OS)明显短于EZH2和Ki-67阴性患者[PFS(月):(53.7±3.6)和(56.8±3.2)vs(62.8±2.4)和(64.3±2.1);OS(月):(56.2±3.0)和(58.7±2.8)vs(64.2±1.9)和(65.8±1.7),均P0.01]。COX比例风险模型多因素分析显示,临床分期、淋巴结转移、EZH2及Ki-67蛋白是影响宫颈癌患者预后的独立危险因素。结论 EZH2和Ki-67异常表达与宫颈癌临床病理特征及预后有一定的相关。     

子宫内膜癌及子宫内膜不典型增生患者免疫组化特征与保留生育疗效的相关因素分析

目的:探讨年轻子宫内膜癌(EC)及子宫内膜不典型增生(AH)患者免疫组化特征与保留生育治疗疗效的关系。方法:回顾分析2010年1月至2020年8月北京大学人民医院收治的EC(40例)及AH(47例)患者的临床资料及免疫组化结果,采用醋酸甲羟孕酮(MPA)或醋酸甲地孕酮(MA)口服,联用促性腺激素释放激素激动剂(GnRH-a)和(或)左炔诺酮宫内缓释系统(LNG-IUS),根据开始治疗后9个月内是否完全缓解(CR)将患者分为组1:≤9个月达CR组;组2:9个月未达CR组(包括PR、NC、PD及复发患者),进行统计学分析。结果:组1使用MPA、MPA+GnRH-a、MPA+LNG-IUS、MPA+GnRH-a+LNG-IUS例数分别为27例、4例、2例、1例,组2使用MA、MPA、MPA+GnRH-a、MPA+LNG-IUS、MPA+GnRH-a+LNG-IUS分别为2例、22例、4例、3例、4例,差异无统计学意义(P0.05)。组1中p16、p53、PTEN阳性表达率分别为81.0%(17/21)、32.0%(8/25)、27.3%(6/22),ER、PR、Ki-67在癌灶中表达率的中位数分别为70%(60%,80%)、80%(50%,90%)、10%(8.75%,20%);组2中p16、p53、PTEN阳性表达率分别为91.7%(22/24)、51.5%(17/33)、28.0%(7/25),ER、PR、Ki-67在癌灶中表达率的中位数分别为70%(50%,80%)、80%(65%,90%)、30%(17.5%,30%)。两组的ER、PR、p16、p53、PTEN表达率比较,差异无统计学意义(P0.05),而组2的Ki-67表达率明显高于组1,差异有统计学意义(P0.05)。Ki-67与p53联合诊断试验:如Ki-6720%且p53定性为阴性,则缓解率为70.6%(12/17),若p53阳性则缓解率为50%(3/6),如Ki-67≥20%,p53定性为阴性或阳性,其缓解率分别仅为26.7%(4/15)和26.3%(5/19)。结论:保留生育治疗前对刮宫标本进行免疫组化染色有助于了解EC与AH患者的预后,Ki-67表达率对保留生育治疗疗效的预测意义较大。Ki-6720%且p53阴性更倾向于疾病缓解,而如果Ki-67≥20%,则不能如期缓解可能性大。     

原发性腹膜恶性肿瘤化疗方案的探讨

目的 比较原发性腹膜恶性肿瘤采用不同化疗方案治疗对患者生存时间的影响。方法 对1995年5月．2005年5月在本院治疗的27例原发性腹膜恶性肿瘤患者的临床病理资料进行回顾性分析。结果 全部患者均施行肿瘤细胞减灭术，术后予以铂类为主的方案化疗。24例患者采用TP（紫杉醇＋顺铂／卡铂）或PAC（顺铂＋阿霉素＋环磷酰胺）方案化疗，其中2例失访，2例尚未完成化疗；另有2例患者采用以铂类为主的其他方案化疗，1例未化疗。总结有完整化疗及随访资料的20例患者的生存情况。TP方案组13例，PAC方案组7例。20例患者初次化疗缓解率80％（完全缓解60％，部分缓解20％），无进展中位生存时间16个月（11。21个月），总体中位生存时间42个月（22．3～61．7个月）。TP方案组和PAC方案组患者的年龄、绝经状况、腹水细胞学检查、手术后残余灶大小、手术分期（沿用卵巢癌FIGO分期标准）、病理类型、化疗疗程及化疗毒副反应均无统计学差异。TP方案组患者无进展中位生存时间19个月，PAC方案组12个月，两者比较无统计学差异；TP方案组和PAC方案组患者的平均生存时间分别为69个月和28个月，两者比较，差异有统计学意义（P〈0．05）。结论 原发性腹膜恶性肿瘤采取肿瘤细胞减灭术及铂类为主的化疗方案可改善预后，TP联合化疗可能优于PAC方案延长患者生存时间。     

子宫内膜癌分子标志物与临床病理特征关系的研究

目的探讨子宫内膜癌中ER、PR、PTEN、p53及Ki-67的表达与临床、病理特征的关系。方法收集200例原发性子宫内膜癌患者的临床病理资料,对其ER、PR、PTEN、p53及Ki-67表达情况进行统计学分析。结果①子宫内膜癌病例中．ER、PR、PTEN、p53的阳性表达率分别为86．5％、85．5％、82．10和49．2％;Ki-67在癌灶中的阳性表达率为4％--95％,平均为46．9％。②妊娠次数与PR阳性表达呈负相关（r=-0．191,P=0．007）,而发病年龄、分娩次数与p53阳性表达呈正相关（r=0．184,P=0．041;r=0．255,P=0．004）。③子宫内膜样腺癌ER、PR、p53阳性率与其他类型子宫内膜癌比较,差异有统计学意义（P〈0,01）。④ER阳性表达与手术病理分期呈负相关（r=-0．155,P=0．028）,其中I期患者ER阳性率高于Ⅱ期及以上患者（P=0．032）。⑤ER、PR阳性表达与组织学分级呈负相关（r=-0．217,P=0．002;r=-0．317,P=0．000）,但p53、Ki-67表达与其呈正相关（r=0．327,P=0．000;r=0．465,P=0．000）。⑥ER阳性表达与肌层浸润深度呈负相关（r=-0．142,P=0．046）,在有无深肌层浸润上ER、PR表达率均有统计学意义（P〈0．05）。结论对子宫内膜活检组织进行分子标志物的分子特征检测,有助于指导临床。     

p16INK4A、p53、Ki-67及ER在宫颈病变组织中的表达及其相关性研究

目的 探讨p16INK4A、p53、Ki-67及雌激素受体(ER)在不同程度宫颈病变中表达及相关性.方法 采用SP法检测宫颈鳞状细胞癌、宫颈上皮内瘤变(CIN)、尖锐湿疣及正常宫颈组织中p16INK4A、p53、Ki-67及ER蛋白的表达.结果 p16INK4A、p53、Ki-67及ER在宫颈鳞癌组中的阳性率分别为100%、86.4%、86.4%及4.6%;在CIN Ⅲ中为92.5%、75.0%、100%、20.0%;在CIN Ⅱ中为90.5%、64.3%、100%及23.9%;在CINⅠ中为71.8%、43.6%、100%、79.5%;在尖锐湿疣组中为39.0%、43.9%、26.9%、61.0%.p16INK4A在宫颈鳞癌、CIN Ⅲ、Ⅱ组中,以强阳性表达为主;尖锐湿疣组仅为弱阳性表达.Ki-67在宫颈鳞癌、CINⅢ组中,以强阳性表达为主.宫颈鳞癌、CINⅢ、Ⅱ、Ⅰ、尖锐湿疣中p16INK4A、p53、Ki-67、ER阳性表达率与对照组比较差异有高度显著性(P＜0.05).结论 p161NK4A、p53蛋白高表达与宫颈鳞癌、CIN的发生发展密切相关;p16INK4A、p53、Ki-67阳性率与宫颈病变严重程度呈正相关,ER的阳性率与其呈负相关.     

女性生殖道同期发生的黏液上皮化生和肿瘤1例并文献复习

目的探讨不同宫颈鳞状上皮内病变患者的p16及Ki-67蛋白的表达及其意义。方法收集宫颈活检和宫颈锥切术资料完整的宫颈鳞状上皮内病变(SIL)患者92例作为研究组,其中26例宫颈上皮内瘤变(CIN)1,23例CIN2,43例CIN3,选择同期宫颈炎症25例作为对照组。采用免疫组织化学法检测宫颈组织中p16蛋白及Ki-67蛋白的表达情况并分析。结果 (1)在不同CIN组织中,p16和Ki-67蛋白阳性表达率明显不同(P 0.001),p16阳性表达率随着CIN严重程度的增加而升高(P 0.05);(2)在不同CIN组织中,p16和Ki-67蛋白共同阳性率明显不同(P 0.001)。p16和Ki-67蛋白阳性表达率随着CIN严重程度的增加而升高(P 0.05)。结论 p16和Ki-67蛋白可以区别不同程度CIN,加强两者的检测可辅助CIN2/3的诊断及预后的判断。     

子宫恶性中胚叶混合瘤和腺肉瘤的EGFR、HER-2/neu、p53、Ki-67抗原的表达

子宫恶性中胚叶混合瘤(MMMT)是一种既含有恶性腺体又有恶性间质的高度恶性肿瘤,而腺肉瘤(AS)一种含有恶性间质和良性体腺体的低浸润性肿瘤。使用免疫组化方法对20例MMMT和6例AS的组织切片进行染色,测定其腺体和间质组织成分中p53蛋白、HER-2/neu蛋白、表皮生长因子受体(EGFR)及Ki-67抗原的过度表达率。PCNA(增生细胞核抗原)染色用于检测Ki-67抗原作为增殖标志物的可靠度。同时还测定了MMMT和AS中ER、PR的频率以及与EGFR过度表达的关系。     

Borderline tumors of the ovary: a clinico-pathologic and immunohistochemical study of 54 cases

OBJECTIVE: To study EGF-R, HER-2/neu (p185), p53, Mib-1 (Ki-67), Bax, Bcl-2, ras expression and ploidy in borderline tumors of the ovary by assessing their frequency, and relationship to histologic type, tumor recurrence and survival. METHODS: Fifty-four patients with borderline tumors were followed 3-140 months (median: 38 months). Paraffin-embedded sections were stained using monoclonal antibodies against EGF-R, HER-2/neu (p185), p53, Mib-1 (Ki-67), Bax, Bcl-2, and ras. The immunohistochemical findings were correlated to histologic subtype, tumor recurrence, and survival. RESULTS: Positivity for EGF-R was found in 24% (13/54), in 22% (12/54) p185 was positive, 9% (5/54) of tumors were p53-positive, Mib-1 (Ki-67)-positivity was demonstrable in 46% (25/54). Expression of Bax, Bcl-2, and ras was found in 37% (20/54), 28% (15/54) and in 7% (4/54) of the cases, respectively. CONCLUSION: The data demonstrate expression of EGF-R, p185/HER-2/neu, p53, Mib-1 (Ki-67), Bax, Bcl-2, and ras in a subgroup of patients with ovarian borderline tumors. Further studies to evaluate their prognostic value are warranted.     

Immunohistochemical comparison of primary peritoneal and primary ovarian serous papillary carcinoma.

Twenty-six patients, meeting strict criteria for primary peritoneal serous papillary carcinoma (PPSPC), were matched to 22 patients with ovarian serous papillary cancer (OSPC) for age and stage. Immunohistochemistry was used to determine the status of estrogen receptors (ER), progesterone receptors (PR), the expression of cell proliferation marker Ki-67, and the overexpression of HER-2/neu and p53 protein. Of the PPSPCs, 53.8% were poorly differentiated, as were 18.2% of the OSPCs (p = 0.012). Positive immunostaining for ER and PR was less in PPSPCs (30.8% and 46.2%, respectively) than OSPCs (72.7% and 90.9%; p = 0.003 and p = 0.001, respectively). Conversely, a significant increase in the expression of Ki-67 was found in PPSPCs (37.7%) versus OSPCs (26.8%) (p = 0.039). The same trend was found for HER-2/neu, being overexpressed in 38.5% of the PPSPC versus 9.1% of the OSPCs (p = 0.019). Overexpression of p53 was found in 30.8% of the PPSPCs and 45.4% of the OSPCs (not significant). There was a significantly worse survival rate for PPSPCs than for OSPCs (p = 0.017), yet none of the studied parameters were significantly correlated with survival within the PPSPC and OSPC groups. The significantly different immunohistochemical expression of ER, PR, Ki-67, and HER-2 in PPSPCs compared with OSPCs suggests that different molecular events may lead to tumorigenesis in these two cancers.     

Influence of chemotherapy on the expression of p53, HER-2/neu and proliferation markers in ovarian cancer.

OBJECTIVE: Mutated p53 and HER-2/neu play a role in the etiology of ovarian cancer. It is important to know whether the expression of these proteins is affected by platinum-containing chemotherapy. STUDY DESIGN: Together with the cell proliferation markers Ki-67 and PCNA, the expression of p53 and HER-2/neu was assessed before and after chemotherapy. Paraffin-embedded tumor sections from 20 patients with ovarian cancer and four patients with benign disorders of the ovaries (controls) were analyzed. The expression of p53 was determined by the antibodies DO-1 and BP53-12. In addition to HER-2/neu and PCNA specific antibodies, MIB-1 was used to detect Ki-67. RESULTS: The expression of all markers was higher in ovarian cancer patients than in non-malignant controls. MIB-1 showed a significant increase of expression after chemotherapy (P=0.002). HER-2/neu, p53 and PCNA also showed a clear increase after treatment, but this was not statistically significant. HER-2/neu is of prognostic relevance with respect to the response to chemotherapy (P=0.005) and survival (P=0.0002). CONCLUSION: The different markers tested all increase after chemotherapy, but the differences are not statistically significant. Low HER-2/neu expression correlates with good outcome at second look.     

Significantly greater expression of ER, PR, and ECAD in advanced-stage low-grade ovarian serous carcinoma as revealed by immunohistochemical analysis.

A 2-tier system that classifies ovarian serous carcinoma (OSC) as low grade or high grade is gaining acceptance. Women with low-grade OSC generally have higher 5-year survival rates than do women with high-grade OSC. We examined the expression of various markers to further understand the molecular differences between low-grade and high-grade OSCs: the potential therapeutic targets or prognostic markers Her-2/neu, estrogen receptor, and progesterone receptor (PR); the metastasis-associated markers cyclin D1 (BCL1), E-cadherin, matrix metalloproteinase (MMP) 2, and MMP-9; and the cell proliferation-associated markers BCL1, Ki-67 antigen (Ki-67), and p53. For this immunohistochemical analysis, we used paraffin-embedded specimens from 47 patients with advanced-stage low-grade OSC and from 49 patients with advanced-stage high-grade OSC. Our results showed that low-grade tumors expressed significantly higher levels of estrogen receptor, PR, and E-cadherin than did high-grade tumors, suggesting the involvement of gonadal steroid hormones, especially in the pathogenesis of low-grade OSC; the PR positivity was also observed in the stromal component of these low-grade tumors. On the other hand, high-grade tumors trended toward increased expression of MMP-9, BCL1, p53, and Ki-67, and robust MMP-9 positivity was observed in the stromal component of these high-grade tumors. These differences may lead to the development of different therapeutic strategies for women with either the low-grade or the high-grade form of OSC.     

Prognostic importance of survivin,Ki-67, and topoisomerase IIα in ovarian carcinoma

Purpose

Stage, tumor grade and histological subtype determine the clinical behavior in ovarian tumors. Some additional factors are related to tumor cell biology and are the useful predictors for identifying the patients with poor prognosis. The aim of this study is to evaluate the prognostic significance of survivin, Ki-67 and Topoisomerase IIα (TOPO IIα) in epithelial ovarian cancer (EOC).

Materials and methods

Seventy-three patients with EOC were included in this study. Survivin, Ki-67 and TOPO IIα expressions were studied by immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections. Nuclear staining for all antibodies was scored on a three-tiered system and more than 10 % staining was accepted as expression. The relationship between the expressions of survivin, Ki-67, TOPO IIα and clinicopathological parameters including age, stage, grade, platinum resistance and survival was evaluated.

Results

Survivin, Ki-67 and TOPO IIα expressions were found in 20, 82 and 86 % of the tumors, respectively. Ki-67 and TOPO IIα expressions were found to be related to poor overall survival (p = 0.005, 0.004, respectively), while survivin expression was not associated with overall survival. There was no association between TOPO IIα and Ki-67 expressions and histological subtype, stage or grade. However, we found an important relationship between TOPO IIα expression and platinum resistance (p = 0.044). Platinum resistance was found to be an independent prognostic factor in EOC.

Conclusion

Ki-67 and TOPO IIα expressions were found to be related to poor overall survival, and TOPO IIα expression was found to be associated with platinum resistance.     

Clinical and molecular comparison between borderline serous ovarian tumors and advanced serous papillary ovarian carcinomas.

The aim of this study was to characterize the clinical and molecular markers of borderline serous ovarian tumors (BSOT), and to study their expression in the progression from benign lesions to advanced serous papillary ovarian carcinomas (SPOC). The clinical records of 20 patients with BSOT and 22 patients with SPOC were reviewed. Specimens from all these cases and from six benign ovarian serous cystadenomas were evaluated for expression of estrogen receptors (ER), progesterone receptors (PR), p53. HER-2/neu and Ki-67 by immunohistochemical techniques. The mean patient age and the age at menarche differed significantly between the compared groups of BSOT and SPOC (p=0.0006 and p=0.0014, respectively). No difference was observed comparing the other clinical parameters. The immunohistochemical analysis demonstrated a significant increase in the expression of ER (100% vs 72.7%), and a significant decrease in the immunoreactivity for p53 (0% vs 45.4%) and Ki-67 (2% vs 26.8%) in cases of BSOT compared with those of SPOC (p=0.007, p=0.0003 and p=0.012, respectively). No significant difference was demonstrated comparing the expression of PR and HER-2/neu. The immunostaining of benign ovarian serous cystadenoma specimens did not differ significantly from immunoreactivity observed in cases of BSOT. According to immunohistochemical analysis, BSOT had much more in common with benign serous tumors than with SPOC. The main difference between BSOT and SPOC was regarding the overexpression of p53 and Ki-67.     

抑制Her-2基因的表达对NK-92细胞杀伤SKOV3细胞活性影响的研究

目的:探讨抑制Her-2基因的表达对NK-92细胞杀伤SKOV3细胞活性的影响。方法:Her-2siRNA质粒在脂质体介导下转染到包装病毒细胞株PT67中,将病毒上清转染SKOV3,经嘌呤霉素筛选得到稳定抑制Her-2基因表达的SKOV3/siRNA-1、SKOV3/siRNA-2细胞株,并分别通过RT-PCR和免疫组化法鉴定抑制Her-2表达的效果。应用LDH法检测NK-92细胞对SKOV3、SKOV3/siRNA-1、SKOV3/siRNA-2、SKOV3/siRNA-neg-ative control的杀伤活性。结果:Her-2/siRNA-1、Her-2/siRNA-2均可有效沉默Her-2mR-NA和蛋白的表达。NK-92细胞对SKOV3、SKOV3/siRNA-negative control的杀伤率分别为21%、20%,而对SKOV3/siRNA-1、SKOV3/siRNA-2的杀伤率分别为33%、45%(P<0·05)。结论:抑制Her-2基因的表达可增强NK-92细胞对SKOV3细胞的杀伤活性。RNA干扰技术联合NK-92细胞为高表达Her-2基因卵巢癌的生物治疗提供了一种新的策略。     

Immunohistochemical analysis of survivin expression in primary breast cancers.

BACKGROUND AND PURPOSE: Survivin, an inhibitor of apoptosis, is expressed in fetal tissues but undetectable in normal adult tissues. It is also expressed in most common human cancers. This study evaluated the expression of survivin in breast cancers. METHODS: A monoclonal anti-survivin antibody B1 was generated. Immunohistochemical staining was performed in 226 paraffin sections of primary breast cancers and correlated with the patients' clinicopathological characteristics. RESULTS: Survivin was expressed in the cytoplasm of tumor cells in 59.3% of breast cancers. Expression of survivin was associated with high histologic grade (p = 0.027), high mitotic count (p = 0.014), positive p53 immunostaining (p = 0.012), neu overexpression (p = 0.018), and with bcl-2 (p = 0.001) and bak (p < 0.001) expression. No correlation was found between survivin expression and age, tumor size, estrogen receptor, progesterone receptor or Bax expression. Survivin expression was not significantly associated with overall or disease-free survival. CONCLUSIONS: Survivin expression is correlated with high histologic grade, high mitotic count, p53 overexpression, and bcl-2 expression in breast cancer. It does not have significance as a marker in predicting overall or disease-free survival.     

The expression of Ki-67, p53, estrogen and progesterone receptors affecting survival in uterine leiomyosarcomas. A clinicopathologic study

OBJECTIVES: To evaluate the level of expression of estrogen receptor (ER), progesterone receptor (PR), p53 and Ki-67 in patients with leiomyosarcoma and to investigate the effect of these and to identify the clinical parameters on prognosis. MATERIALS AND METHODS: Twenty-four patients operated for LMS of uterine origin between 1994 and 2003 at Istanbul Medical School, Department of Obstetrics and Gynecology and Division of Gynecologic Oncology constituted our study group. The data of all patients were updated via mail or phone. The effects of stage, grade, chemotherapy, radiotherapy, number of mitoses, presence of necrosis, Ki-67 and p53 expression, presence of estrogen and progesterone receptors on survival were evaluated. RESULTS: The mean follow-up period of patients is 30.42 +/- 25.15 months. The mean overall survival for all LMS patients was estimated to be 48.4 +/- 10.38 months. The cumulative survival ratio in the 33rd month was 33.08. Age, menopausal status, history of prior radiotherapy, number of mitoses had no statistically significant effect on overall survival in our study although stage had a significant effect. Finding of greater than 10% steroid receptor expression has a positive effect on survival ([ER P = 0.019; log rank = 5.49] and [PR P = 0.023; log rank = 5.14]). The median value of Ki-67 was calculated to be 30. There was a survival advantage in patients with Ki-67 expression (P = 0.034; log rank = 4.49) below the median value. p53 levels had no significant effect on survival (P = 0.336; log rank = 0.92). CONCLUSION: Surgical staging is an important prognostic factor in LMS patients, while number of mitoses and grade of the tumor also seem to affect prognosis. Contrary to the current literature, our findings suggest that estrogen and progesterone receptor positivity greater than 10% may be associated with a better prognosis.