卵巢浆液性和粘液性交界瘤的临床病理分析

目的：观察卵巢交界瘤的临床病理学特点,探索肿瘤不同组织学改变的意义。方法：对45例卵巢浆液性和粘液性交界瘤进行回顾性分析,肿瘤分期按国际妇产科联合会（FIGO）标准,Ⅰ期34例,Ⅱ期4例,Ⅲ期7例。结果：45例卵巢浆液性和粘液性交界瘤占同期卵巢上皮恶性肿瘤的25．4％,浆液性同粘液性交界瘤的比为1：1．3,11例生长于卵巢表面的浆液性交界瘤中,9例出现腹膜种植,2例为浸润性种植,7例为非浸润性种植。2例浆液性交界瘤和1例粘液性交界瘤分别于术后5、4和1年复发。33例交界瘤经2－9年随访,按Kaplan-Meier法5年生存率为100％。结论：卵巢浆液性交界瘤预后较好,卵巢表面生长的浆液性交界瘤常伴有腹膜种植。     

卵巢微乳头浆液性交界瘤4例临床病理分析

1996年Burks[1]报道在卵巢浆液性交界瘤内有一类微乳头状交界瘤,肿瘤虽无明显卵巢间质浸润,但常伴有浸润性腹膜种植,病变多进行性发展为浸润性肿瘤.Burks称其为卵巢微乳头浆液性癌(micropapillary serous carcinoma, MPSC).此后许多学者[2～4]对MPSC进行了研究,并提出了不同的看法.Deavers[5]认为MPSC常伴浸润性种植,复发率高,但其总生存率和浆液性交界瘤相当,因而将它保留在交界的范围内是正确的.我们复查了近10年来诊断为卵巢浆液性交界瘤和卵巢浆液性癌的病例,发现符合MPSC的诊断标准有4例,本文称之为微乳头浆液性交界瘤(micropapillary serous borderline tumors, MSBTs),现将其临床病理学特点报道如下.     

交界性胃肠道间质瘤279例临床病理学分析

目的 阐述交界性胃肠道间质瘤(gastrointestinal stromal tumors,GISTs)的特征并重新评估目前广泛应用于GISTs的美国国家卫生研究所(NIH)共识标准.方法 回顾性分析840名患者的病史资料及手术切除标本.结果 筛除485例恶性GISTs及76例假定的良性GISTs,剩余的279例GISTs归为交界性GISTs,其中223例随访1～31年.2例患者局部复发,随后经过单纯手术切除治愈.5年无瘤生存率和总生存率分别为99%和100%.形态学上,交界性GISTs的典型特征为富于细胞、中度异型性、低核分裂活性(＜10个/50 HPF)或较大肿瘤体积.依据NIH共识标准,279例中,极低危险度组13例,低危组164例,中危组71例,高危组31例,但各组间的无瘤生存率差异无显著性(P=0.681).结论 交界性GISTs具有介于良恶性GISTs之间的临床及形态学特征.部分交界性GISTs表现出恶性潜能,需长期随访.NIH 共识标准基于肿瘤体积及核分裂象划分的危险度等级并不适用于评估交界性GISTs的生物学行为.     

S100A4蛋白在卵巢浆液性腺癌中的表达及其临床意义

目的: 分析S100A4蛋白在卵巢浆液性腺癌中的表达及其与临床病理因素和预后的关系,探讨其在卵巢浆液性腺癌侵袭转移过程中的作用及判断卵巢浆液性腺癌患者预后的价值。方法: 用免疫组化方法检测S100A4蛋白在卵巢浆液性腺癌、卵巢浆液性腺瘤及卵巢交界性浆液性腺瘤组织中的表达,分析S100A4蛋白的表达与卵巢浆液性腺癌各临床病理因素及生存预后的关系。结果: S100A4蛋白表达定位在肿瘤细胞的细胞质和细胞核,在卵巢浆液性腺癌、卵巢交界性浆液性腺瘤和卵巢浆液性腺瘤组织中的高表达率分别为78%、30%和27%,S100A4蛋白在卵巢浆液性腺癌组织中的高表达率高于其它两个对照组,差异有统计学意义。S100A4蛋白表达与卵巢浆液性腺癌患者的病理分级、治疗后是否复发有关(均P＜0.05)。单因素分析显示患者无疾病进展时间和总生存时间均与S100A4蛋白表达有关(P＜0.05)。多因素Cox回归分析显示术后残留病灶大小和病理分级是影响卵巢浆液性腺癌预后的独立因素。结论: S100A4蛋白表达上调在卵巢浆液性腺癌的发生过程中可能起一定作用。病理分级高的卵巢浆液性腺癌细胞可能部分通过上调S100A4蛋白表达增强其侵袭转移能力。S100A4蛋白可能成为对卵巢浆液性腺癌患者复发风险预测和预后判断的指标之一。     

卵巢交界性浆液性肿瘤17例临床病理分析

目的对卵巢交界性浆液性肿瘤的临床特征、病理学特点进行分析,探讨其诊断及鉴别诊断。方法收集17例卵巢交界性浆液性肿瘤患者的临床资料,对组织病理学表现进行分析,并复习相关文献。结果17例卵巢交界性浆液性肿瘤患者,年龄42~65岁,平均年龄51.2岁。17例患者中有4例患者常有下腹不适和腹胀、尿频等症状,有5例患者有经期延长与出血量多的症状,还有2例患者因肿瘤破溃导致急腹症。结论卵巢交界性浆液性肿瘤的患者,预后相当好,5年生存率为90%。但仍有10%的患者预后不好。     

卵巢Brenner肿瘤14例临床病理分析

目的探讨卵巢Brenner肿瘤的临床病理学特征、诊断和鉴别诊断。方法回顾性分析9例良性Brenner瘤、1例交界性Brenner瘤、4例恶性Brenner瘤的临床病理资料,并复习相关文献。结果 9例良性Brenner瘤特征是移行细胞型细胞组成的实性或囊性细胞巢,位于纤维瘤样间质内,囊腔内衬移行细胞型细胞、纤毛细胞、黏液细胞、立方细胞或扁平细胞,细胞无异型,细胞核卵圆形,核仁小而明显,部分有明显核沟。1例交界性Brenner瘤与良性Brenner瘤形态相近,但上皮细胞增殖程度超过良性Brenner瘤,细胞巢大小不一,层次增多,细胞轻度异型,但无间质浸润。4例恶性Brenner瘤有明显的间质浸润,并可见良性或交界性Brenner瘤成分。肿瘤细胞明显异型,核大深染,核分裂象易见,其中1例肿瘤累及输卵管和大网膜。免疫表型:14例肿瘤中CK7、p63均呈阳性,GATA-3阳性但部分低分化肿瘤区域失表达,CK20、Pax-8、WT-1均呈阴性,但黏液上皮化生区CK20呈阳性,Ki-67增殖指数恶性浸润区为20%～70%,交界性为3%,良性3%。结论卵巢Brenner肿瘤属于少见的卵巢上皮源性肿瘤,确诊需根据组织病理学特征和免疫表型。肿瘤细胞异型程度和有无间质浸润是良恶性Brenner瘤的鉴别关键。诊断恶性Brenner瘤必须有良性或交界性Brenner成分,与卵巢其他肿瘤的鉴别需结合临床病史、组织学特征和免疫表型。     

卵巢浆液性交界瘤近期讨论的诊断问题

卵巢浆液性交界瘤（serous-borderline ovarian tumrs．SBOT）肿瘤分型、腹膜种植以及浆液性癌的诊断一直意见不一。2003年在美国Bethesda成立了卵巢交界瘤工作组，对以往文献中报道的卵巢交界瘤的报道资料进行了分析。Bell认为卵巢浆液性微乳头交界瘤（micripapillary type serons-bordedine ovarian tumors）与典型的S-BOT比较，差异不明显，因而将前者留在交界瘤范围内比较适当。     

胃肠道间质瘤中p16、p27、Ki-67表达

目的探讨胃肠道间质瘤中p16、p27和Ki67表达与临床预后的关系。方法根据核分裂象的多少、肿瘤体积的大小及有无浸润等将胃肠道间质瘤划分为良性、交界性和恶性,并运用免疫组化SP方法检测p16、p27和Ki67在胃肠道间质瘤中的表达,并统计分析其良性、交界性、恶性和复发死亡病例中的表达差异。结果p16、p27和Ki67的阳性表达率分别为48%、26%和24%。p16在良、恶性中的表达无明显差异,但在良性和交界性中的表达与复发和转移相关;p27低标记指数和Ki67高标记指数与复发和转移相关。结论p16、p27和Ki67在胃肠道间质瘤中的表达对判断预后有价值。     

卵巢黏液性交界性肿瘤中K-ras基因突变及p21 ras蛋白的表达

目的：观察卵巢黏液性交界性肿瘤中K-ras基因突变及p21 ras蛋白的表达,探讨卵巢黏液性交界性肿瘤的发病机制及靶基因治疗的可能。方法采用PCR-RFLP法和免疫组化EliVision法分别检测40例卵巢黏液性交界性囊腺瘤、40例卵巢黏液性囊腺癌和20例卵巢黏液性囊腺瘤中K-ras基因突变和p21 ras蛋白的表达。结果 K-ras基因在卵巢黏液性囊腺瘤、黏液性交界性囊腺瘤和黏液性囊腺癌中的突变率分别为0、37.5%、7.5%,交界组突变率明显高于其他两组,差异有统计学意义( P<0.01)。 K-ras基因突变在卵巢黏液性交界性肿瘤年龄分组中突变,差异有统计学意义(P<0.05)。 p21ras蛋白在卵巢黏液性囊腺瘤、黏液性交界性囊腺瘤和黏液性囊腺癌中阳性率分别为5%、45%、10%,交界组阳性率明显高于其他两组,差异有统计学意义(P <0.01)。结论 K-ras基因突变及p21ras蛋白表达可能是卵巢黏液性交界性肿瘤形成的原因之一,有利于卵巢黏液性交界性肿瘤的判断,还可为临床作为靶向治疗药物分析提供病理学基础。     

外分泌胰腺的交界性肿瘤

传统上外分泌胰腺的肿瘤一般分为良性和恶性两大类 ,但随着对胰腺肿瘤认识的深入 ,也提出了胰腺交界性肿瘤的概念 ,新版ＷＨＯ肿瘤分类[1] 也列出了外分泌胰腺的交界性肿瘤的类型。目前认为外分泌胰腺的交界性肿瘤包括 :交界性粘液性囊腺瘤 ,导管内乳头状粘液腺瘤伴中度不典型增生 ,胰腺的实性 假乳头瘤。胰腺导管上皮的中度不典型增生也应属交界性病变。一、粘液性囊性肿瘤 (包括交界性粘液性囊腺瘤 )为一类由产生粘液的上皮细胞形成的囊性胰腺肿瘤。过去一直分为良性的粘液性囊腺瘤和恶性的粘液性囊腺癌。1978年Ｃｏｍｐａｇｎｏ和Ｏｅｒ…     

卵巢粘液性及浆液性囊腺瘤癌胚抗原的免疫组化研究

以CEA单克隆抗体,双PAP法研究卵巢粘液性和浆液性囊腺瘤组织内CEA的定位。结果表明:良性瘤23例,CEA全部(-)。交界性肿瘤中粘液性22例,CEA(+)者21例;浆液性15例,CEA(+)者7例。恶性肿瘤中粘液性23例,CEA(+)者18例,浆液性37例,CEA(+)者7例。由于粘液性交界性肿瘤有较高的CEA检出率,可作为诊断参考指标。     

Fascin and EMMPRIN expression in primary mucinous tumors of ovary: A tissue microarray study

ObjectivesThe aim of this study was to compare the expressions of fascin and EMMPRIN in primary malignant, borderline and benign mucinous ovarian tumors, and to investigate the relationship of these markers with tumor progression and their applicability to differential diagnosis.Materials and methodsAn immunohistochemical study was performed for fascin and EMMPRIN using the tissue microarray technique. Eighty-one cases were included in the study; there were 37 benign, 25 borderline and 19 malignant primary mucinous ovarian tumors. For each case, a total staining score was determined, consisting of scores for extent of staining and intensity of staining. The cases were allocated to negative, weakly positive and strongly positive staining categories, according to the total staining score.ResultsBoth of the markers were significantly negative in benign tumors as compared with borderline and malignant tumors. There was no significant difference between borderline and malignant groups for both markers. Sixty-eight percent of malignant tumors were stained positive by fascin, while this rate was 40% for borderline mucinous tumors. All malignant tumors were strongly stained positive for EMMPRIN, while this rate was 92% for borderline mucinous tumors. The rest of the cases stained weakly positive. No significant difference in staining score was found between fascin and EMMPRIN expression.ConclusionsIn ovarian primary mucinous tumors, fascin and EMMPRIN may play an important role in tumor progression from benign tumor to carcinoma. In that context, EMMPRIN and fascin expression may have potential application in the differential diagnosis of some diagnostically problematic mucinous ovarian tumors. However, the differential diagnostic applicability of EMMPRIN appears to be more limited than that of fascin due to its wide spectrum of staining in mucinous ovarian tumors.     

Increased expression of OCIA domain containing 2 during stepwise progression of ovarian mucinous tumor

Ovarian cancer immunoreactive antigen domain containing 2 (OCIAD2) has been reported to show cancer-specific expression in early invasive lung adenocarcinoma. OCIAD2 shows high homology with OCIAD1, which was originally immunoscreened from ascites of a patient with ovarian cancer and found to be a tumor-specific protein. Therefore, like OCIAD1, OCIAD2 is expected to show high immunoreactivity in ovarian tumors. In this study, we examined the expression pattern of OCIAD2 in 117 ovarian mucinous tumors, and confirmed that it was more highly expressed in borderline tumor and carcinoma (51/74 cases, 69%) than in adenoma (6/43 cases, 14%). The immunoreactivity of OCIAD2 in borderline tumor and carcinoma was more specific than that of OCIAD1 (adenoma, 21/43 cases, 49%), and more sensitive than that of CEA (borderline tumor and carcinoma, 35/74 cases, 47%). Like OCIAD1, OCIAD2 is a cancer-related protein and its expression level increases during the course of malignant progression and is thought to be a very useful marker for evaluating the malignancy of ovarian mucinous tumors.     

The presence and location of epithelial implants and implants with epithelial proliferation may predict a higher risk of recurrence in serous borderline ovarian tumors: a clinicopathologic study of 188 cases

Serous borderline ovarian tumors have a favorable prognosis, and recurrences are uncommon. The factors influencing recurrence are not fully understood. Epithelial inclusions are identified in serous borderline ovarian tumors and are traditionally referred to as epithelial implants, which often show epithelial proliferation. We investigated whether the presence of epithelial implant and epithelial proliferation portends a higher risk for recurrence of serous borderline ovarian tumors in patients who underwent surgical removal of these tumors. Also examined was whether the anatomical site of epithelial implant and epithelial proliferation was associated with a higher risk of recurrence. One hundred eighty-eight cases of pure serous or predominantly serous borderline ovarian tumors were studied for the presence of epithelial implant and epithelial proliferation, and subsequent recurrences were recorded. The anatomical sites of epithelial implant and epithelial proliferation were compared between serous borderline ovarian tumors with or without recurrence. Statistical analysis was performed using the χ(2) test. Epithelial implant was noted in 106 cases (56%), and epithelial proliferation, in 26 cases (14%). Recurrence was identified in 10.4% cases with epithelial implant and 23% cases with epithelial proliferation. Statistical analyses of patients with recurrence showed significant differences in the following groups: epithelial implant versus no epithelial implant (P < .025) and epithelial proliferation versus no epithelial implant (P < .001). Recurrence rates were higher in the epithelial implant and epithelial proliferation groups as compared with no epithelial implant or epithelial proliferation groups. Epithelial implant and epithelial proliferation appear to pose a statistically significantly higher risk of recurrence in serous borderline ovarian tumors as compared with the absence of epithelial implant. Although the anatomical location of such implants was not significantly associated with a higher risk, the presence of epithelial proliferation at multiple sites was more frequently seen in recurrent serous borderline ovarian tumors.     

Foxp3,TGF-β1,VEGF,CD3-ζ和IL-10在卵巢上皮性癌中的表达与预后相关分析

 目的 研究叉头蛋白 3（Foxp3）、转化生长因子 β1（TGF- β1）、血管内皮生长因子（VEGF）、CD3-ζ、IL-10 等免疫抑制因子的表达强度与卵巢上皮性癌预后的相关性。 方法 采用免疫组织化学 SP 法，检测 5 种因子分别在79 例卵巢上皮性癌、16 例卵巢交界性肿瘤、30 例卵巢良性肿瘤和 20 例正常卵巢组织中的表达情况，应用计算机图像分析系统和人工半定量评分方法分别对 Foxp3、TGF-β1 和 VEGF、CD3-ζ、IL-10 的表达结果进行评判，并分析 5 种因子在卵巢上皮性癌中表达强度相互之间的相关性，及其表达强度与卵巢上皮性癌预后的相关性。 结果 TGF-β1 在正常卵巢组织中的表达强度明显低于卵巢上皮性癌、卵巢交界性肿瘤和卵巢良性肿瘤组织（P = 0.009），而其他 4 种因子在卵巢上皮性癌组织中的表达强度均明显高于卵巢交界性肿瘤、卵巢良性肿瘤和正常卵巢组织（均 P < 0.001）。TGF-β1 的表达强度只与 CD3-ζ 有关（P = 0.001），CD3-ζ 的表达强度与其他 4 种因子均有关（P < 0.01），Foxp3、VEGF、IL-10 的表达强度相互之间均具有明显的相关性（均 P < 0.01）。Foxp3 和 TGF-β1 的表达强度均与卵巢上皮性癌的总生存期有关（P 值分别为 0.010、0.013），而 VEGF、CD3-ζ、IL-10 的表达强度均与卵巢上皮性癌的总生存期无相关性；Logistic 回归分析显示，TGF-β1、术后残余和化疗规范性为卵巢上皮癌的 3 个重要预后因素（P < 0.05）；在卵巢上皮性癌中，TGF-β1 的表达强度与患者年龄、FIGO 分期、病理分级、术后残余、淋巴结转移以及化疗规范性等病理特征均无相关性。 结论 5 种免疫抑制因子在卵巢上皮性癌组织中均呈高表达，Foxp3 和 TGF-β1 的表达强度与卵巢上皮性癌的预后有关。     

Peritoneal serous borderline tumors: report of two cases

Two cases of serous borderline tumors of the peritoneum are reported. These rare tumors may show variable histological features. The lack of peritoneal invasion, which may be difficult to assess, with minimal or no ovarian involvement are major features for the diagnosis. These tumors should be distinguished from other peritoneal neoplasms such as serous carcinomas because of their good prognosis after surgical therapy alone.     

卵巢粘液性肿瘤组织发生的初步探讨

目的：初步探讨卵巢粘液性肿瘤（ＯＭＴ）的组织发生。方法：用组织化学染色方法观察９１例ＯＭＴ上皮的粘液分泌。按粘液性质将上皮分为３型：胃型、肠型和中间型。并将肿瘤分为简单型及混合型。结果：良性５６例中,４５例为混合型,其中２２例由３种上皮成份组成,２３例含２种上皮,另有１１例为简单型。中间型、胃型及肠型３种上皮在良性肿瘤中的出现频率分别是４０／５６、３５／５６、２９／５６。２１例交界性、１４例恶性Ｏ     

Genetic alterations of serous borderline tumors of the ovary compared to stage I serous ovarian carcinomas

Borderline tumors of the ovary comprise 10-20% of all epithelial ovarian tumors, and are placed between clearly benign and obviously malignant ovarian tumors. The issue of whether borderline tumors are precursors of invasive carcinoma or distinct clinical entities, however, is still the subject of discussion. To increase our understanding in relation to this issue, the aim of our study was to analyze both serous borderline and invasive ovarian tumors, and to investigate early carcinogenesis in serous ovarian tumors. Using comparative genomic hybridization, we compared cytogenetic changes in borderline ovarian tumors and stage I invasive tumors. The average number of genetic alterations differed significantly between the borderline and the invasive tumors (1.9 and 9.2, respectively). The most common genetic alterations among the borderline tumors were loss of chromosome 17, 20q, and 18p, and gain of 12p13 approximately q23. These changes were also found among the invasive tumors in a similar percentage. In conclusion, we found four distinct cytogenetic alterations that might be early events in serous ovarian tumors, and that might also characterize a subgroup of borderline ovarian tumors that may have the potential to progress and develop malignancy.     

叶酸受体α在卵巢上皮性肿瘤中的表达

目的 探讨卵巢上皮性肿瘤中叶酸受体(FR)α的表达及其临床病理学意义.方法 制备包括86例卵巢癌及29例卵巢交界性肿瘤的组织芯片,采用免疫组织化学EnVision法检测上述肿瘤组织中FRα的表达情况,同时采用即时PCR检测40例新鲜冷冻卵巢癌组织以及14例卵巢交界性肿瘤组织中FRα mRNA的表达情况.分析卵巢上皮性肿瘤中FRα表达水平与肿瘤的组织类型、不同发病模式以及临床分期的关系.结果 免疫组织化学染色结果显示,86例卵巢癌中有40例(46.5%)对FRα呈明确阳性反应,其中浆液性癌阳性表达率最高,为62.7%(32/51),高于其他组织类型的癌(P=0.000).按照卵巢癌发病模式区分,Ⅱ型卵巢癌FRα的表达明显高于Ⅰ型卵巢癌,差异具有统计学意义(P=0.001).卵巢癌组FRα表达阳性率高于交界性肿瘤(46.5%∶27.6%),但差异无统计学意义(P=0.074).卵巢癌组FRα的表达与临床分期无相关性(P=0.498).相似的结果也见于采用即时PCR检测FRα mRNA的表达情况:卵巢癌组FRα mRNA表达值高于交界性肿瘤组(P=0.000),在交界性肿瘤中,浆液型mRNA表达值高于黏液型,差异具有统计学意义(P=0.007).结论 卵巢上皮性肿瘤中FRα呈高表达,特别是在恶性肿瘤和浆液性肿瘤中.