卵巢肿瘤组织中端粒酶逆转录酶的原位表达

目的　探讨卵巢肿瘤组织中端粒酶逆转录酶 (TRT)的表达及其与凋亡基因 p5 3蛋白和bcl 2基因的关系。方法　应用免疫组织化学S P法检测 78例卵巢肿瘤组织中TRT及p5 3、bcl 2的表达 ,结果进行统计学分析。结果　TRT在不同卵巢肿瘤组中的表达差异有显著性 ,在卵巢上皮组织肿瘤中良性、交界性和恶性肿瘤组的阳性表达分别为 6 7%、5 7 2 %和 85 % ,在卵巢生殖细胞肿瘤中良性与恶性的阳性表达为 10 %和 81 8% ,TRT的表达随着肿瘤恶性度增高呈现阳性率和阳性强度递增现象 ,两者比较差异有显著性 (P <0 0 1) ;卵巢恶性上皮组织肿瘤中 p5 3蛋白和bcl 2基因的阳性表达率分别为 90 %和80 % ,相关分析显示TRT与 p5 3和bcl 2的表达密切相关 (P <0 0 1)。结论　TRT的高表达与卵巢恶性肿瘤有密切关系 ,卵巢肿瘤组织中TRT与p5 3、bcl 2的表达呈正相关 ,TRT可作为卵巢肿瘤恶性度的一个指标。     

Molecular Genetic Evidence Supporting the Clonality and Appendiceal Origin of Pseudomyxoma Peritonei in Women

Pseudomyxoma peritonei (PMP) is a poorly understood condition characterized by mucinous ascites and multifocal peritoneal mucinous tumors. Women with PMP often have mucinous tumors involving both the appendix and the ovaries. Several previous histopathological and immunohistochemical studies of PMP have suggested that most, if not all, cases of PMP in women are derived from mucinous adenomas of the appendix rather than from primary ovarian tumors. A few studies of the molecular genetics of PMP have been recently reported. However, these studies analyzed only a small number of cases and some included a heterogeneous group of mucinous tumors, including both benign and malignant appendiceal and ovarian tumors. We analyzed K-ras mutations and allelic losses of chromosomes 18q, 17p, 5q, and 6q in a substantial number of morphologically uniform cases of PMP with synchronous ovarian and appendiceal tumors as well as in appendiceal mucinous adenomas (MAs) and ovarian mucinous tumors of low malignant potential (MLMPs) unassociated with PMP. Each of the 16 PMP cases (100%) analyzed demonstrated identical K-ras mutations in the appendiceal adenoma and corresponding synchronous ovarian tumor. K-ras mutations were identified in 11 of 16 (69%) appendiceal MAs unassociated with PMP and in 12 of 16 (75%) ovarian MLMPs unassociated with PMP. Two PMP cases showed identical allelic losses in the matched ovarian and appendiceal tumors. A discordant pattern of allelic loss between the ovarian and appendiceal tumors at one or two of the loci tested was observed in six PMP cases. In all but one instance, LOH was observed in the ovarian tumor, whereas both alleles were retained in the matched appendiceal lesion, suggesting tumor progression in a secondary (metastatic) site. Our findings strongly support the conclusion that mucinous tumors involving the appendix and ovaries in women with PMP are clonal and derived from a single site, most likely the appendix.     

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.     

Malignant effusions: from diagnosis to biology

Serous effusions are a frequently encountered clinical manifestation of metastatic disease, with breast, ovarian, and lung carcinomas and malignant mesothelioma (MM) leading the list. Recently, extensive research has resulted in expansion of the antibody panel that is available for effusion diagnosis, thereby reducing the risk for error. Despite this progress, relatively little has been done in way of understanding the biology of cancer cells in effusions, especially those of nonovarian origin. The diagnosis of a malignant effusion signifies disease progression and is associated with a worse prognosis regardless of the tumor site of origin. However, survival is much more variable with ovarian cancer compared with other tumors. Furthermore, cancer cells of different origins differ considerably in their biology and have unique phenotypic and genotypic characteristics. This review summarizes the current knowledge in this field and presents a model for the study of tumor metastasis and disease progression, through large comparative studies of malignant cells in effusions, primary tumors, and solid metastases. The case also is made for potential applications of this rapidly evolving body of knowledge in the diagnosis, classification, and prediction of biological behavior of processes resulting in cryptic effusions at the clinical level.     

卵巢肿瘤对妊娠结局的影响

目的探讨妊娠合并卵巢肿瘤的特征、诊断和治疗对妊娠结局的影响。方法回顾性分析144例妊娠合并卵巢肿瘤的临床、病理及随访资料。结果患者年龄20~41岁,平均28.28岁。择期或剖宫产同时切除卵巢肿瘤103例,因并发症急诊手术41例。良性肿瘤136例,恶性肿瘤8例(5.55%),病理类型以囊性成熟性畸胎瘤为主共74例(51.39%)。足月妊娠91例(63.19%),人工流产37例,自然流产14例,早产2例,胎儿宫内窘迫及新生儿窒息共18例。2例卵巢恶性肿瘤因延期化疗,术后短期内复发。结论妊娠合并卵巢肿瘤影响患者的生育意愿,早孕期人工终止妊娠率高。卵巢肿瘤蒂扭转是急诊手术的主要原因,导致良性肿瘤单侧附件切除率高,术后易引起流产。孕14~22w或剖宫产同时切除卵巢肿瘤对妊娠结局无明显不利影响,恶性肿瘤应按非孕期原则治疗。     

腹膜假黏液瘤

目的;探讨腹膜假黏液瘤（PMP）的病理形态和免疫组织化学特点,病理诊断、发生及预后。方法：复习11例PMP的临床资料并进行随访,分别对线例腹膜及原发瘤进行光镜和免疫组织化学观察。结果：11例PMP男女比为3：8;年龄36－76岁（平均56岁）。随访1例术后2年死亡,1例失访,余8例1－60个月健在。11例均表现腹腔大量黏液和腹膜多发包裹黏液性肿瘤;伴有阑尾黏液性肿瘤者8例,其中5例女性同时有卵巢黏液性病变;结肠黏液性肿瘤1例,伴有卵巢黏液性病变;单纯卵巢黏液性肿瘤2例。CK7、CK20和CA125标记示同一病例其阑尾和（或）卵巢及腹膜肿瘤标记结果常一致。结论：对PMP作病理诊断时,应综合分析做出良性、低度恶性或恶性PMP的诊断。阑尾与PMP的发生可能有更加直接的关系。PMP的预后取决于其生长速度。     

Mural nodules of anaplastic carcinoma in bilateral ovarian borderline mucinous cystadenoma: a case report

The occurrence of mural nodules in serous or mucinous ovarian tumors is not frequent but is currently well established. Mural nodules can developed in benign, borderline or malignant tumors. They can be reactive, benign or malignant. In these situations, the nodule may be carcinomatous, sarcomatous or mixed. Thus, the prognosis of the ovarian tumor can be dramatically modified by the presence of this nodule. About twenty cases of mural nodules of anaplastic carcinoma have been described. We report an additional case of two mural nodules of anaplastic carcinoma associated with bilateral ovarian borderline mucinous tumor. This tumor was synchronous with a renal cell carcinoma. We give details about the classification, the differential diagnoses and prognosis of these nodules.     

尿精眯与血清CA125联合检测诊断卵巢恶性肿瘤的价值

探讨尿精眯(SPD)与血清CA125联合检测对卵巢恶性肿瘤的诊断价值.采用聚酰胺薄膜层析法分别测定20名对照组和47例妇科盆腔肿块患者尿SPD水平,同时用化学发光免疫法检测两组患者的血清CA125水平.结果表明,卵巢恶性肿瘤组患者尿SPD和血清CA125水平(679.49±368.39 μg/mg肌酐,251.23±172.48 U/L)明显高于对照组(218.76±88.35 μg/mg,13.96±12.07 U/L)和卵巢良性肿瘤组患者(204.62±85.26 μg/mg肌酐,25.29±31.6 3U/L).两标记物对卵巢恶性肿瘤的灵敏度分别为80.95%和71.43%,若二者联合灵敏度可高达90.48%.尿SPD和血清CA125联合检测可提高卵巢恶性肿瘤的诊断准确率.     

Ovarian carcinoma: current diagnostic principles

Ovarian cancer is the most common cause of death from a gynecologic cancer. The most common types of ovarian cancer are carcinomas of surface epithelial-stromal origin. Ovarian carcinomas are a heterogeneous group of neoplasms. Based on proposed different pathways of tumorigenesis, these tumors are divided into two broad subgroups (type I and II) with different biologic behaviour, prognosis and response to therapy. Type I tumors include low-grade serous adenocarcinoma, low-grade endometrioid adenocarcinoma, mucinous adenocarcinoma, malignant Brenner tumor and some clear cell carcinomas. These tumors are low-grade neoplasms evolving from a defined precursor lesion. Type II tumors are high-grade neoplasms including undifferentiated carcinoma, high-grade serous adenocarcinoma, high-grade endometrioid adenocarcinoma, malignant mixed Müllerian tumor and probably some clear cell carcinomas. At present, the histological type of ovarian carcinoma has only limited impact on the management of these tumors. However, with progress towards the type-specific treatment of ovarian carcinoma, accurate histopathological diagnosis of ovarian carcinoma becomes increasingly important. In this review we summarize recent advances in the histopathological diagnosis of ovarian carcinoma. Moreover, we mention genetic changes in different types of ovarian carcinoma.     

Ovarian epithelial tumors of borderline malignancy]

Ovarian tumor is known to show histological variation. Each tumor shows various clinical behavior. Ovarian epithelial tumors consist of several types of histological findings. Epithelial tumors can be classified into benign, borderline malignancy and malignant for their biological behavior. Recently the therapeutic effectiveness against ovarian cancer is increasing in order to establish the operation technique and development of chemotherapeutic method with cisplatin. Therefore it is important that borderline malignant tumors which are said to have a good prognosis be defined from obviously malignant tumors to evaluate accurately the effectiveness of the therapy against the ovarian cancer. On the other hand, borderline malignant tumors with characters of a malignant tumor, must be distinguished from benign adenoma because long-term follow up is required. However, it is difficult to make an exact histological diagnosis of benign adenoma, borderline malignancy and malignancy because the histological criteria of borderline malignancy is lacking in concreteness. The histological criteria should be defined more clearly and concretely. For example, mitotic counts per 10 HPF of borderline malignancy and DNA ploidy. Next, because of good prognosis, we need a quick therapeutic guide line for borderline malignancy, especially for stage I and young women.     

Increasing expression of serine protease matriptase in ovarian tumors: tissue microarray analysis of immunostaining score with clinicopathological parameters.

Matriptase is a type II transmembrane serine protease expressed by cells of surface epithelial origin, including epithelial ovarian tumor cells. Matriptase cleaves and activates proteins implicated in the progression of cancer and represents a potential prognostic and therapeutic target. The aim of this study was to examine the expression of matriptase in ovarian tumors and to assign clinicopathological correlations. Immunohistochemical analysis of matriptase was performed in tissue microarrays of 164 ovarian neoplasms including 84 serous adenocarcinomas, 23 mucinous adenocarcinomas, 10 endometrioid adenocarcinomas, six yolk sac tumors, 12 clear cell carcinomas, six dysgerminomas, eight granulosa cell tumors, four transitional cell carcinomas, five fibromas, and six Brenner tumors. All ovarian tumors except the fibromas and Brenner tumors showed significant expression of matriptase. The matriptase scores were significantly higher in the tumors than in their nontumor counterparts (304+/-26 for serous adenocarcinoma; 361+/-28 for mucinous adenocarcinoma; 254+/-17 for endometrioid adenocarcinoma; 205+/-19 for yolk sac tumor; 162+/-16 for clear cell carcinoma; 109+/-11 for dysgerminoma; 105+/-9 for granulosa cell tumor; and 226+/-18 for transitional cell carcinoma). Matriptase scores in serous adenocarcinoma were correlated with TNM stage and FIGO stage. Our findings demonstrate for the first time that matriptase is overexpressed in many malignant ovarian tumors. It may be a novel biomarker for diagnosis and treatment of malignant ovarian tumors.     

良、恶性卵巢肿瘤C－Ha－rasl位点的等位基因型与杂合性缺失

为了探讨Ｃ－Ｈａ－ｒａｓｌ位点的等位基因型与杂合性缺失在卵巢癌发生中的意义，应用Ｓｏｕｔｈｅｒｎ印迹技术，在１７例良、恶性卵巢肿瘤患者中研究Ｃ－Ｈａ－ｒａｓｌ位点的多态性和等位片段缺失。结果表明，在ＢａｍＨＩ酶切、Ｃ－Ｈａ－ｒａｓｌ探针杂交的放射自显影图上显示７．８ｋｂ（Ｌ）和６．８ｋｂ（Ｓ）两个等位片段，基因型ＳＳ的个体在恶性卵巢肿瘤组的比例（７／１１）显著高于良性肿瘤组（２／６）（Ｐ＜０．０１）；在４例正常组织的ＬＳ杂合子患者中，１例患者的卵巢癌细胞出现等位片段杂合性丢失（ｌｏｓｓｏｆｈｅｔｅｒｏｚｙｇｏｓｉｔｙ，ＬＯＨ）和重排，并且有高度恶性的表型。本结果提示：等位片段Ｓ的钝合子和ＬＯＨ后的半合子（ｈｅｍｉｚｙｙｏｔｅ）较等位片段Ｌ纯合子和ＬＳ杂合子有更大的恶性卵巢肿瘤的易感性。     

卵巢肿瘤组织中端粒酶活性的表达

目的分析端粒酶活性在卵巢肿瘤中的表达,探讨端粒酶活性作为卵巢肿瘤诊断肿瘤标记物的意义。方法取冰冻肿瘤组织,采用端粒重复序列扩增法（Telomeric Repeat Amplication Protocol）,结合银染,共测定了27例卵巢癌、5例良性卵巢肿瘤、22例卵巢癌癌旁组织以及12例正常卵巢组织中端粒酶活性,并分析其与组织分级、FIGO分期、病理类型以及有无转移的关系。PCR产物以采用聚丙烯酰胺凝胶电泳分析,以出现特征性的6-bp间隔的特征性阶梯状条带为阳性。出现〉100bp的条带为强阳性,出现〈99bp的条带为中低阳性。结果本实验共对66份标本进行了检测,12例正常卵巢组织中,仅有2例表达端粒酶活性;5例卵巢良性肿瘤中,1例表达端粒酶弱阳性。27例卵巢恶性肿瘤标本中,有23例表达端粒酶活性（其中强阳性16例）;在检测的22例卵巢上皮癌的癌旁组织中,有12例表达端粒酶弱阳性。卵巢恶性肿瘤的端粒酶活性表达阳性率显著高于卵巢良性肿瘤（P=0.0090）和正常卵巢（P=0.0000）。Ⅰ-Ⅱ期患者端粒酶活性阳性率71%,Ⅲ-Ⅳ期患者端粒酶活性阳性率90%（P=0.269）。而强阳性率Ⅲ-Ⅳ期明显高于Ⅰ-Ⅱ期（P=0.009）。在肿瘤类型和组织学分级中,端粒酶阳性表达率均没有显著差异。结论在卵巢恶性肿瘤组织中端粒酶活性有较高的表达率;早期和晚期卵巢肿瘤组织中端粒酶活性阳性率没有明显差异,但晚期卵巢肿瘤组织中的端粒酶活性程度较高;端粒酶活性有可能作为早期诊断卵巢肿瘤的标记物之一,并可以作为卵巢肿瘤判断预后的指标。     

Simultaneous strumal ovarii and lymphoma with emphasis on the diagnostic usefulness of immunohistochemical stains.

Strumal ovarii has been rarely associated with other tumors, such as carcinoid tumor, carcinoma, and primary ovarian malignant lymphoma. We report the coexistence of a strumal ovarii and ovarian involvement by malignant lymphoma in a 70-year-old woman. The tumors were detected 10 years following exposure to ionizing radiation during the Chernobyl nuclear tragedy.     

Periodical changes in diagnosis and treatment of ovarian tumors]

Malignant ovarian tumors are one of the most rapidly changing gynecological malignancies concerning diagnosis and treatment during the last 20 years. Clinical cases of about 1,000 malignant ovarian tumors including borderline malignancies enlisted in the Tokai Ovarian Cancer Study Group were analyzed for periodical improvement. A comparison between the 460 cases treated in 1974-1979 and the 574 cases treated in 1980-1985, revealed a nearly 20% improvement in the 5-year survival rate. Also another comparison was made for ovarian carcinoma according to the clinical stage. Periodical improvement was shown in all clinical stages in almost the same amount, which was about 20% or more. The 5-year death rate was compared in accordance with age of patient and histological type of the tumor. Dominant progression was observed in younger generation under forty years of age, and in serous carcinoma and yolk sac tumor. However, no progression was observed for patients in their sixties and unclassified carcinoma. Periodical changes of findings in autopsy were compared between cases autopsied in 1968 and in 1988, according to the annual paper reported by Japan Pathological Society. Number of autopsied cases for malignant ovarian tumors were increased 3 times in 1988. In 1968, nearly 60% of the malignant ovarian tumors were treated by doctors in internal medicine, surgery and radiology etc., rather than gynecology, which was partly because the primary site of the cancer was unknown during the clinical course and partly because the gynecologist gave up treatment of patients in advanced cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential diagnosis, prognostic factors, and clinical treatment of proliferative Brenner tumor of the ovary

Brenner tumors are rare ovarian tumors displaying benign, borderline or proliferative, and malignant variants. The case of a 63-year-old woman with a proliferative Brenner tumor is presented and the histomorphological differential diagnosis of this tumor entity is compared to that of its benign and malignant counterparts. Light microscopy, immunohistochemistry, and electron microscopy were performed to allow discrimination from the other subtypes. Despite a considerable overlap of pathological features the differential diagnosis of proliferative Brenner tumor could be established. Electron microscopy allowed assessment of characteristic infoldings of the nuclear membrane that proved to be a valuable ultrastructural criterion. Considering that the vast majority of Brenner tumors are benign, precise identification of the small proportion of malignant tumors allows the extent of surgical therapy to be adapted.     

卵巢黏液性囊性肿瘤伴实性附壁结节

目的：探讨卵巢黏液性囊性肿瘤伴实性附壁结节的临床病理学特点。方法：对2例卵巢黏液性囊性肿瘤进行光镜观察和免疫组化染色并复习文献。结果：1例卵巢黏液性交界性乳头状囊腺瘤伴实性附壁恶性纤维组织细胞瘤结节，结节内瘤细胞呈多形性。1例卵巢黏液性囊腺瘤伴实性附壁间变性癌结节；间变性癌结节内瘤细胞体积较大，胞质丰富，嗜酸，少数胞质透明，排列呈巢或索状；免疫表型：EMA和cytokeratin阳性。恶纤组结节中肿瘤细胞AACT和vimentin阳性。结论：免疫组化有助于卵巢黏液性囊性肿瘤伴实性附壁结节的诊断及鉴别诊断。     

Ultrastructural study of benign, low-malignant potential (LMP), and malignant ovarian tumors

Ultrastructural characteristics of benign, low-malignant potential (LMP), and malignant ovarian tumors were investigated, considering the aspects of histologic subtypes and histologic grading. In addition, the histogenesis of ovarian cancer was histologically investigated in an attempt to elucidate whether malignant tumor was generated from benign or LMP tumor, or whether it was generated de novo from normal tissues. Although all the benign, LMP, and malignant tumors appeared to be derived from Mullerian duct in serous tumors, the origin of endometrioid or mucinous tumor could not be ultrastructurally clarified. However, there was ultrastructural similarity between benign and malignant tumors among serous, endometrioid, and mucinous tumors, and it was suggested that benign adenoma may be the developmental origin of malignant tumors regardless of the histologic subtype. In addition, the investigation of endometrioid tumors revealed that the differences of histologic grading in malignant tumors reflected the ultrastructural differences, and that G1 tumor had an ultrastructure that was more similar to that of benign and LMP tumors than to that of G2 tumor.     

Gonadal teratomas: a review and speculation

Teratomas of the ovary and testis are confusing because, despite histologic similarities, they exhibit different biologic behaviors, depending mostly on the site of occurrence and the age of the patient. Thus, most ovarian teratomas are benign, and most testicular teratomas are malignant, with the exception of those occurring in children. These general statements, however, do not hold true for ovarian teratomas that are "immature" or exhibit "malignant transformation" and for dermoid and epidermoid cysts of the testis, categories of ovarian and testicular teratomas that are malignant and benign, respectively. This review concentrates on some of the "newer" observations concerning these interesting and confusing neoplasms, including diagnostically deceptive patterns. It is the author's opinion that much of the confusion regarding gonadal teratomas can be clarified by the concept that the usual ovarian teratoma derives from a benign germ cell in a parthenogenetic-like fashion, whereas the typical postpubertal testicular example derives from a malignant germ cell, mostly after evolution of that originally malignant cell to an invasive germ cell tumor (ie, embryonal carcinoma, yolk sac tumor, etc). The postpubertal testicular teratomas can therefore be thought of as an end-stage pattern of differentiation of a malignant germ cell tumor. The pediatric testicular teratomas, as well as dermoid and epidermoid cysts of the testis, however, must derive from benign germ cells, in a fashion similar to most ovarian teratomas. The teratomatous components of mixed germ cell tumors of the ovary, on the other hand, likely have a pathogenesis similar to that of postpubertal testicular teratomas.     

HER-2/neu oncogene amplification by fluorescence in situ hybridization in epithelial tumors of the ovary

HER-2/neu gene amplification and protein overexpression have been associated with prognosis in breast, lung and prostate cancers but have not been extensively studied in ovarian carcinoma. For the study, we selected 5-micron-thick, formalin-fixed, paraffin-embedded tissue sections from 74 cases of ovarian epithelial tumors of low malignant potential and ovarian carcinoma. Tumors were graded and staged and evaluated for amplification of the HER-2/neu gene by fluorescence in situ hybridization. HER-2/neu amplifications was present in 3 of 13 serous, mucinous, and endometrioid epithelial tumors of low malignant potential and in 40 of 61 epithelial carcinomas. In the carcinoma group, amplification did not correlate with stage, grade, or tumor type. Mean follow-up was 31 months; 1 patient with a low malignant potential tumor and 32 patients with carcinomas died of disease. On univariate and multivariate analysis, survival correlated with stage of disease but not with HER-2/neu amplification. HER-2/neu amplification by fluorescence in situ hybridization can be performed on tissue sections of ovarian neoplasms; amplification is uncommon in ovarian tumors of low malignant potential, but is present in 66% of ovarian epithelial carcinomas. HER-2/neu amplification did not predict outcome in ovarian epithelial neoplasia but may have an important role in tumor development.