Numb蛋白在卵巢浆液性肿瘤中的表达及临床意义

目的检测Numb蛋白在卵巢浆液性肿瘤组织中的表达及其临床意义。方法用免疫组织化方法检测Numb蛋白在卵巢浆液性囊腺癌、交界性浆液性囊腺瘤、浆液性囊腺瘤及正常卵巢组织中的表达情况,并与患者的临床病理资料进行分析。结果Numb蛋白在卵巢浆液性囊腺癌中表达阳性率明显低于卵巢正常组织和卵巢浆液性囊腺瘤及交界性浆液性囊腺瘤的阳性率(P0.01),但与肿瘤分化程度、临床病理分期、淋巴结转移及年龄均无明显相关性(P0.05)。结论Numb蛋白在卵巢浆液性囊腺癌中低表达,可能参与浆液性囊腺癌的发生过程。     

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。     

卵巢浆液性交界性肿瘤中clusterin的表达

目的探讨凋亡抑制因子clusterin在卵巢浆液性肿瘤中发生、发展的作用及其与bcl-2、Ki-67表达的关系。方法免疫组化sP法检测clusterin、bcl-2、Ki-67在20例卵巢浆液性囊腺瘤，28例浆液性交界性肿瘤，26例浆液性囊腺癌标本中的表达。结果clusterin在囊腺瘤、交界性肿瘤、囊腺癌中的阳性率分别为40％，67．9％，96．2％。囊腺癌中的clusterin与Ki-67的表达水平均明显高于囊腺瘤（P〈0．05）和SBOT（P〈0．05）。交界性肿瘤中有腹水的患者clusterin阳性率要明显高于无腹水者（P=0．0390），Ki-67在有腹膜种植的患者阳性率要明显高于无腹膜种植者（P=0．0473）。且两者的表达成正相关。结论clusterin基因可能通过抑制凋亡在卵巢浆液性肿瘤的发生发展中起重要作用。clusterin与Ki-67结合起来分析可能作为鉴别SBOT与浆液性癌的辅助指标。     

卵巢浆液性肿瘤中IQGAP1与E-cadherin表达的检测

目的探讨上皮性钙黏素(E-cadherin)与具有IQ结构域的人Ras GTP激活蛋白相关蛋白1(IQGAP1)在卵巢浆液性肿瘤中的表达及其临床意义。方法分别用免疫组织化学SP法和Western blot法检测20例卵巢浆液性囊腺癌、10例卵巢交界性浆液性囊腺瘤、10例卵巢浆液性囊腺瘤以及10例正常卵巢组织中E-cadherin和IQGAP1的蛋白表达。结果 E-cadherin蛋白在浆液性囊腺瘤中表达最高,明显高于正常卵巢组织和浆液性囊腺癌组织(P0.05),其均值高于交界性囊腺癌,无统计学意义。IQGAP1在卵巢浆液性囊腺癌中表达较正常卵巢组织、良性及交界性肿瘤组织均增高(P0.05);免疫组织化学染色证实IQGAP1在浆液性囊腺癌中以胞膜表达为主,而在良性肿瘤中以胞质表达为主。结论 E-cadherin和IQGAP1在卵巢浆液性瘤高表达,可联合用于卵巢浆液性肿瘤的免疫组化诊断。     

ataxin-3在卵巢浆液性肿瘤中的表达及其临床意义

目的检测ataxin-3在卵巢浆液性肿瘤中的表达及临床意义。方法采用免疫组化SP法检测ataxin-3在各组卵巢浆液性肿瘤中表达情况。结果ataxin-3在卵巢低级别浆液性囊腺癌中表达水平明显高于卵巢浆液性囊腺瘤、交界性浆液性囊腺瘤、高级别浆液性囊腺癌中的表达水平,但后三者之间无明显差异(P0.05),ataxin-3表达与卵巢浆液性囊腺癌的分化程度呈负相关,与其它临床病理因素均不存在相关性(P0.05)。结论ataxin-3可能参与卵巢低级别浆液性囊腺癌的发生机制,可能成为其早期诊断指标和治疗靶点。     

卵巢良性和恶性粘液性囊腺瘤酸性粘蛋白的组化改变

用4种酸性粘蛋白组织化学染色法,观察90例卵巢良性和恶性粘渡性囊腺瘤酸性粘蛋白的含量和成分。发现粘液性囊腺癌酸性粘蛋白含量明显高于交界性粘液性囊腺瘤和钻液性囊腺瘤。绝大多数粘液性囊腺瘤酸性粘蛋白的主要成分是唾液酸粘蛋白,或唾液酸和硫酸两种粘蛋白的混合,仅少数瘤含有较多硫酸粘蛋白。与囊腺癌上皮比较,良性囊腺瘤上皮中唾液酸粘蛋白含量增多,或两种酸性粘蛋白均减少。据认为:①当囊腺瘤恶变时,酸性粘蛋白逐渐增加;②唾液酸粘蛋白(部分肿瘤含硫酸粘蛋白)增多是卵巢粘液性囊腺癌的组化特点;③酸性粘蛋白含量可能与肿瘤生物学行为有关。     

HDAC1和HDAC6蛋白过表达在卵巢浆液性癌中的临床病理学意义

目的探讨组蛋白去乙酰化酶(histone deacetylase,HDAC)1和6蛋白表达检测在卵巢浆液性癌中的临床病理学意义。方法选取147例卵巢病变的存档蜡块标本,其中包括39例卵巢浆液性囊腺瘤26例卵巢浆液性交界性囊腺瘤和82例卵巢浆液性囊腺癌。应用免疫组化EnVision法检测HDAC1和HDAC6基因蛋白在上述卵巢病变组织中的表达水平,并分析其蛋白检测的临床病理学意义。结果 HDAC1和HDAC6蛋白分别为胞核和胞质染色,HDAC1蛋白强阳性表达率在卵巢浆液性囊腺瘤、交界性浆液性肿瘤和浆液性囊腺癌中分别为7.7%(3/39)、65.4%(17/26)和80.5%(66/82);HDAC6蛋白的强阳性表达在39例卵巢浆液性囊腺瘤中完全阴性,而在交界性浆液性肿瘤中为34.6%(9/26)、在浆液性囊腺癌中则高达86.6%(71/86),差异均具有统计学意义。结论 HDAC1和HDAC6蛋白在卵巢癌发生发展过程中起重要作用,对于卵巢浆液性癌的诊断具有重要的辅助意义,有望成为卵巢癌治疗的新靶点。     

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。     

卵巢黏液性肿瘤中EGFR表达和K-RAS基因的突变

目的 研究卵巢黏液性肿瘤中表皮生长因子受体(epidermal growth factor receptor,EGFR)蛋白的表达及K-RAS基因的突变,探讨卵巢黏液性肿瘤的发病机制及靶基因治疗的可行性.方法 应用免疫组化PV 9000两步法和PCR-RFLP法分别检测20例卵巢黏液性囊腺瘤、40例卵巢黏液性交界性囊腺瘤和40例卵巢黏液性囊腺癌中EGFR蛋白的表达和K-RAS基因的突变情况.结果 EGFR在卵巢黏液性囊腺瘤、黏液性交界性囊腺瘤和囊腺癌中的阳性表达率分别为0、37.5%、67.5%(P<0.01).K-RAS在卵巢黏液性囊腺瘤、黏液性交界性囊腺瘤和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2组,但卵巢囊腺瘤与囊腺癌比较,差异无统计学意义(P>0.05).EGFR与卵巢黏液性囊腺癌的临床分期、病理分级、患者年龄无关(P<0.05),与肿瘤的大小相关(P<0.05).EGFR与卵巢黏液性交界性肿瘤临床病理分期、肿瘤大小、患者年龄无关(P>0.05).K-RAS基因突变与卵巢黏液性交界性肿瘤临床病理分期、肿瘤大小无关(P>0.05),与患者年龄相关(P<0.05).EGFR的表达和K-RAS基因的突变在卵巢黏液性交界性肿瘤中无相关性(P>0.05).结论 EGFR对卵巢黏液性交界性囊腺瘤和卵巢黏液性囊腺癌的形成起到了一定的作用,而K-RAS基因则可能是卵巢黏液性交界性囊腺瘤形成的一个重要因素.     

NQO1过表达在卵巢黏液性囊腺癌预后评估中的意义

目的:探讨NAD(P)H醌氧化还原酶1[NAD(P)H-quinone oxidoreductase 1,NQO1]过表达在卵巢黏液性囊腺癌临床预后评估中的意义。方法:应用免疫组化En Vision法检测NQO1蛋白在162例卵巢黏液性囊腺癌组织、35例卵巢黏液性囊腺瘤组织和29例正常卵巢上皮组织中的表达,并分析其过表达与卵巢黏液性囊腺癌临床病理学特点之间的关系,通过Kaplan-Meier方法进行生存分析。结果:NQO1蛋白在卵巢黏液性囊腺癌组织中的阳性率及强阳性率分别为85.8%和64.2%,显著高于卵巢黏液性囊腺瘤和正常卵巢上皮组织(P0.01)。卡方检验结果显示,NQO1蛋白高表达与卵巢黏液性囊腺癌组织学分级和FIGO分期密切相关(P0.05)。Kaplan-Meier生存分析显示,NQO1蛋白高表达的卵巢黏液性囊腺癌患者总生存期和无病生存期均明显低于NQO1蛋白低表达患者。结论:NQO1蛋白在卵巢黏液性囊腺癌组织中呈高表达,可能成为卵巢黏液性囊腺癌预后评估的有效生物学指标。     

Cystic neoplasms of the pancreas: A clinical and radiological study of eight cases

Summary Four patients with benign serous cystadenoma, one with mucinous cystadenoma, and three with mucinous cystadenocarcinoma treated in the university hospital of Göttingen between 1985 and 1988 were investigated. The main initial symptoms of these cystic tumors were abdominal pain (7/8), weight loss (3/8), maldigestion (3/8), and palpable abdominal mass (3/8), while laboratory investigations revealed nonspecific alterations (elevated ESR, mild hypochromic anemia). CA 19-9 was elevated in two patients, one of whom had cystadenocarcinoma; CEA also was elevated in this patient only. In all cases size, localization, and cystic character of the tumors were shown clearly by sonography and computed tomography; fine needle biopsy helped to distinguish between serous and mucinous cystadenoma in four of six cases. Because of their malignant potential, total extirpation of mucinous cystic tumors is the treatment of choice, while serous cystadenomas are benign and therefore may be treated conservatively in uncomplicated cases or high-risk patients.Abbreviations M male - F female - path. pathologic - papill. papillary - chron. chronic - US ultrasound sonography - CT computed tomography - ERP endoscopic retrograde pancreaticography Dedicated to Prof. Fritz Scheler on the occasion of his 65th birthday.     

Expression and mutational analysis of c-kit in ovarian surface epithelial tumors

Coexpression of Kit ligand and c-kit has been reported in some gynecologic tumors. To determine whether imatinib mesylate is useful in ovarian epithelial tumors, we performed immunohistochemical and mutational analysis. The cases consisted of 33 cases, which included 13 serous cystadenocarcinomas, 1 borderline serous tumor, 8 mucinous cystadenocarcinomas, 6 borderline mucinous tumors and 5 clear cell carcinomas. Five cases of serous cystadenoma and 5 cases of mucinous cystadenoma were also included. In the immunohistochemical study, 3 cases (3/6, 50%) of borderline mucinous cystic tumor and two cases (2/8, 25%) of mucinous cystadenocarcinoma show positive staining for KIT protein. Only one case (1/13, 7.7%) of serous cystadenocarcinoma had positive staining. On mutational analysis, no mutation was identified at exon 11. However, two cases of borderline mucinous tumors and one case of mucinous cystadenocarcinoma had mutations at exon 17. In these cases, the immunohistochemistry also shows focal positive staining at epithelial component. Although, KIT protein expression showed higher incidence in mucinous tumors than serous tumors, they lack KIT-activating mutations in exon 11. Thus, ovarian surface epithelial tumors are unlikely to respond to imatinib mesylate.     

卵巢囊腺肿瘤的凝集素受体分布

55 cases of ovarian cystadenoma and cystadenocarcinoma were investigated with a panel of twelve various lectins and ABC technique. Results showed that RCA and WGA reacted with all the tumors, indicating that these two lectins are possibly functional differential markers of both ovarian mucinous and serous tumors. LCA, DBA and SJA might be of considerable help in differential diagnosis of serous cystadenoma and cystadenocarcinoma. PSA probably was a marker indicating malignant change of mucinous cystadenmas. Since there were different reactivities in mucinous and serous cystadenoma, SJA, DBA and SBA might be considered as the functional markers in differentiating these two different types of ovarian cystadenoma.     

Fine-needle aspiration cytology of neoplastic cysts of the pancreas

Herein is reported the cytologic features of four cases of cystic neoplasms of the pancreas as seen in fine-needle aspirates. Cytologically, the cases fall into two distinct groups: mucinous cystic neoplasm and serous cystadenoma. The aspirates from the mucinous cystic neoplasms characteristically showed columnar mucus-secreting epithelial cells, some of which were arranged in a papilloglandular pattern, with abundant mucous material in the background. The aspirates from the serous cystadenoma yielded small sheets of cuboidal cells with small nuclei and clear cytoplasm, without a background of mucous material. This cytologic division corresponds closely to the histologic classification proposed by Compagno and Oertel and hence is of prognostic and therapeutic value. The diagnostic challenges confronted by the cytopathologist are (1) to differentiate neoplastic cysts from the inflammatory pseudocysts; (2) to differentiate neoplastic epithelium from the normal epithelium of the bowel and pancreatic ducts; and (3) to differentiate mucinous cystic neoplasms from serous cystadenomas.     

Macrocystic serous cystadenocarcinoma of the pancreas: the first report of a new pattern of pancreatic carcinoma

Cystic pancreatic neoplasms are rare and include mucinous and microcystic cystadenoma (carcinomas) and the recently described macrocystic adenoma. Their accurate diagnosis is difficult by radiology, and histopathology remains the modality of choice. The case of a 42-year-old woman presenting with a gradually enlarging abdominal mass is reported. Imaging studies revealed a large unilocular cystic lesion in the pancreas. An exploratory laparotomy was done with excision of the cyst along with pancreas. Numerous microscopic sections revealed a serous neoplasm with atypical nuclear features and focal invasion of the cyst wall. A final pathological diagnosis of macrocystic serous cystadenocarcinoma of the pancreas was made. The patient has been doing well two years after surgery. This is the first case of a macrocystic serous cystadenocarcinoma of the pancreas, highlighting the need for extensive sampling of all cystic lesions of the pancreas in order to reach a correct diagnosis.     

Endocrine cells in hepatobiliary cystadenomas and cystadenocarcinomas

We investigated the distribution of endocrine cells in hepatobiliary cystadenoma (n=5, two associated with mesenchymal stroma) and cystadenocarcinoma (n=3) immunohistochemically. In normal livers (n=20) and livers affected by hepatolithiasis (n=15) used as controls, endocrine cells revealed by chromogranin immunostaining were located exclusively in normal or proliferating intrahepatic peribiliary glands. In the eight cases of hepatobiliary cystadenoma and cystadenocarcinoma, endocrine cells were present in four cases (50%) (1 cystadenoma, 1 cystadenoma with mesenchymal stroma, and 2 cystadenocarcinomas). Endocrine cells tended to be located beneath and among the columnar epithelial cells. Intrahepatic peribiliary glands were located in the vicinity of cystadenoma or cystadenocarcinoma in six (75%) of the eight cases, and they frequently showed cystic dilatation and contained endocrine cells. Intrahepatic peribiliary glands were located in the vicinity of the endocrine cells in all cystadenomas and cystadenocarcinomas that were positive for endocrine cells. These data show that about 50% of hepatobiliary cystadenomas and cystadenocarcinomas contain endocrine cells and suggest that hepatobiliary cystadenoma and cystadenocarcinoma may originate from intrahepatic peribiliary glands.     

Measurement of CA125, carcinoembryonic antigen, and alpha-fetoprotein in ovarian cyst fluid: diagnostic adjunct to cytology.

This study used CA125, carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP) to classify ovarian cysts by measuring the levels of the three antigens; this information was useful when fluid obtained through laparoscopic puncture of ovarian cysts was submitted for cytologic examination from patients for whom tissue was unavailable for classification. We studied 136 consecutive cyst fluids (108 benign, 28 malignant) and correlated the findings with the tissue diagnosis. All three antigens were very low (CEA, less than 0.5 ng/ml; CA125, 55-2,143 mu/ml; and AFP, less than 4.8 ng/ml) in follicular and lutein cysts. Markedly elevated CA125 (296-1,950,000 mu/ml) and low CEA (0.5-220 ng/ml) and AFP (less than 4.8 ng/ml) levels were seen in patients with serous neoplasms, both benign and malignant. Elevated CEA (greater than 600 ng/ml) and CA125 (56-65,330 mu/ml) levels were seen in primary mucinous cystadenoma and cystadenocarcinoma. Two patients with colonic carcinoma metastatic to the ovary had an elevated CEA (greater than 600 ng/ml) and a normal CA125. Only one patient, with a malignant teratoma, had an elevated AFP. The adjunctive use of CEA and CA125 is recommended for the classification of ovarian cysts.     

Macrocystic serous cystadenoma of the pancreas: a morphologic variant differing from microcystic adenoma.

The term "microcystic adenoma" of the pancreas has gained nearly universal acceptance among pathologists owing to the characteristic gross and microscopic features of this tumor. The possible existence of macrocystic variants of serous cystadenoma has been largely ignored in the literature. We report five cases of macrocystic serous cystadenoma of the pancreas, two of which were of the unilocular type. These tumors exhibited distinctly different macroscopic features from microcystic adenoma, which created diagnostic difficulties for both the radiologist and pathologist. Computed tomography scans on all five cases were thought to represent either mucinous cystic neoplasms or pseudocysts and the tumors were misclassified in two of three cases on which intraoperative frozen sections were performed. In our opinion, microcystic and macrocystic serous tumors represent morphologic variants of the same benign pancreatic neoplasm and we suggest that the term "serous cystadenoma" be used to encompass all variants of this benign neoplasm.     

Prognostic significance of HLA-DR antigen in serous ovarian tumors

Abstract. The antigens encoded by the major histocompability complex (HLA-DR) are cell glycoproteins that play a fundamental role in the regulation of the immune response. The prognosis of ovarian cancer is dependent on the histological type and on the clinical stage at diagnosis. Our study reports the value of HLA-DR antigen as a prognostic marker of ovarian serous adenocarcinoma. We studied 31 cases of serous ovarian cystadenoma, 12 cases of serous ovarian borderline cystadenoma, and 39 cases of well-differentiated cystadenocarcinoma for HLA-DR monoclonal antigen. We also studied the T helper marker (CD4) in the tumor stroma of the relevant cases, given that it is now known that the dependence of immune responsiveness on the class II antigens reflects the central role of these molecules in presenting antigen to T helper cells. HLA-DR was expressed in 20 of 31 cystadenomas (64.5%), 4 of 12 borderline tumors (33.3%), and in 10 of 39 invasive carcinomas (25.6%). CD4 was expressed in 9 of 31 cystadenomas (29%), 5 of 12 borderline tumors (42%), and in 26 of 39 invasive carcinomas (67%). There was a statistically significant difference for the two examined antigens in cystadenomas (p<0.001) and invasive carcinomas (p<0.001), whereas there was no statistical difference in borderline tumors (p<0.5). The results showed decreased expression of HLA-DR and increased expression of CD4 as the lesion progressed to malignancy. The aberrant expression of HLA-DR by epithelial cells of cystadenomas, of borderline tumors, and of invasive adenocarcinomas agrees with the hypothesis of the adenoma/adenocarcinoma sequence. The immune attraction mechanism by low HLADR signaling seems to be of minor importance in the malignant and metastatic potential of serous ovarian tumors.