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1.
Prognostic significance of HLA-DR antigen in serous ovarian tumors   总被引:2,自引:0,他引:2  
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.  相似文献   

2.
DEK overexpression in uterine cervical cancers   总被引:2,自引:0,他引:2  
Wu Q  Li Z  Lin H  Han L  Liu S  Lin Z 《Pathology international》2008,58(6):378-382
The purpose of the present paper was to investigate the significance of DEK protein expression in uterine cervical lesions and its relationship with HPV infection status. DEK protein expression was studied in 253 cervical lesions, including 30 non-neoplastic cervix with or without squamous metaplasia, 64 cervical intra-epithelial neoplasias (CIN; CIN-1, n  = 28; CIN-2, n  = 17; CIN-3, n  = 19), 102 squamous cell carcinomas (SCC), 51 adenocarcinomas, and six adenosquamous cell carcinomas (adenoSCC) on immunohistochemistry. For comparison, HPV-positive and -negative cervical cancer cell lines were also included. The HPV screening was performed using TaKaRa polymerase chain reaction. On immunohistochemistry DEK was found to be negative in all 30 non-neoplastic cervical epithelia, but it was positive in 96.1% of SCC (98/102), 92.2% of adenocarcinomas (47/51), 100% of adenoSCC (6/6), 85.7% of CIN-1 (24/28), 94.1% of CIN-2 (16/17), and 89.5% of CIN-3 (17/19). There was no significant difference between HPV-positive and -negative cervical lesions. Also, strongly positive staining was observed in all aforementioned cervical cancer cell lines regardless of HPV infection, according to immunocytochemistry. In summary, DEK plays an important role in the carcinogenesis of cervical cancers, and can be helpful for early diagnosis, and is a potential therapeutic target.  相似文献   

3.
目的:探讨神经突起生长导向因子Netrin-1在卵巢浆液性癌( ovarian serous carcinoma,OSC)中的表达及其临床病理意义。方法采用免疫组化EnVision法检测20例卵巢良性浆液性囊腺瘤、13例卵巢交界性浆液性囊腺瘤和32例OSC中Ne-trin-1蛋白的表达,分析Netrin-1蛋白表达与OSC临床病理特征的关系。结果 Netrin-1在OSC中的阳性率明显高于卵巢交界性和良性浆液性囊腺瘤(P<0.01)。OSC组织中Netrin-1表达与肿瘤分化程度及临床分期有关(P<0.05),与患者年龄、发病部位、肿瘤大小及有无盆腔淋巴结转移无关( P>0.05)。Kap1an-Meier生存分析显示,Netrin-1高表达患者5年生存率显著低于Netrin-1低表达患者( P<0.05)。结论 Netrin-1在OSC组织中高表达,提示其可能与肿瘤的发生、发展有关,可作为OSC患者预后判断的辅助指标。  相似文献   

4.
Liu S  Wang X  Sun F  Kong J  Li Z  Lin Z 《Pathology international》2012,62(3):176-181
To investigate the clinicopathological significance of DEK overexpression in breast cancers, a total of 196 cases, including 20 of normal tissues, 12 of intraductal hyperplasia, 31 of ductal carcinoma in situ (DCIS) and 133 of invasive ductal carcinoma of the breast, were selected from the Department of Pathology, Yanbian Tumor Hospital for immunohistochemical staining of DEK, estrogen (ER), progesterone (PR) and Ki-67 proteins. In results, DEK protein had higher positivity in DCIS, compared with the adjacent normal breast tissues. Also, DEK protein was strongly positive in invasive ductal carcinoma of the breast on immunohistochemistry, which was significantly higher than normal breast tissues. However, only two (2/12) cases of intraductal hyperplasia of the breast showed positive staining for DEK protein. Additionally, DEK overexpression was significantly correlated with the increased proliferating index of Ki-67. For the histological grade, DEK positive rate was only 39.6% in G1 breast cancers, but significantly higher in G2 (92.3%) and G3 (97.0%) cases (P<0.05). Also, a strongly positive rate of DEK was lower in Stage-0 (21.4%) and Stage-I (40.9%) compared with Stage-IIa (87.5%), Stage-IIb (89.7%) and Stage-IIIa (92.3%) (P<0.05). And DEK protein showed higher expression level in < 3 years disease free survival breast cancers than it did in ≥ 3 years disease free survival cases (P<0.05). However, no statistically difference was found among DEK expression, lymph node metastasis, and ER and PR expressions. In conclusion, DEK overexpression appears to be associated with breast cancer progression and DEK may potentially be used as a breast cancer biomarker for the early diagnosis, prognostic evaluation and therapeutic target for breast cancer.  相似文献   

5.
Clarification of the pathogenic relationships existing among ovarian cystadenomas, tumors of low malignant potential (LMP) and various adenocarcinoma types, a series of 29 mucinous and 19 serous ovarian tumors including adenomas, LMP tumors and adenocarcinomas were examined. P53 protein was detected by the streptavidin-biotin method and point mutation of K-ras codon 12 was detected by polymerase chain reaction-restriction fragment length polymorphism analysis. P53 overexpression was observed more frequently in serous adenocarcinomas (5/8, 63%) than in mucinous adenocarcinomas (2/9, 22%) and was correlated with the malignant potential of serous tumors. Furthermore, the proportion of P53-positive cells was significantly higher in serous adenocarcinomas than in mucinous adenocarcinomas. P53 overexpression may therefore be closely related to the early events of carcinogenesis in serous tumors. Although mutation of the K-ras oncogene appears to be an important event in the early tumorigenesis of mucinous tumors, mutation of the K-ras oncogene in serous tumors may be dependent on morphology. Different complex pathways of oncogene and/or tumor suppressor gene abnormalities may be involved in the development of mucinous and serous adenocarcinomas.  相似文献   

6.

Introduction

There is a need to assess the value of the novel potentially useful biomarkers in ovarian tumors. The aim of study was to assess the value of sAgNOR analysis in ovarian serous epithelial tumors.

Material and methods

The analysis was performed in ovaries from 113 patients treated operatively due to serous ovarian tumors (30 adenomas, 14 borderline tumors and 69 cancers). After silver staining of paraffin specimens from surgery, sAgNOR in tumor cells was analyzed. Additionally, the value of the argyrophilic nucleolar organizer region area/nucleus ratio (sAgNOR) in the prediction of disease-free survival (DFS) and overall survival (OS) in 52 patients with serous ovarian cancer with complete follow-ups in November 2009 was evaluated. Age, grading, radicality of surgery and FIGO staging were analyzed as additional factors.

Results

sAgNOR in adenomas, borderline tumors and cancers was in the following ranges: (0.73 ±0.23) × 106, (0.81 ±0.18) × 106 and (0.96 ±0.33) × 106 [AgNOR/cm2] respectively. In cancers from G1 to G3 sAgNOR was (1.02 ±0.32) × 106 (G1), (0.98 ±0.37) × 106 (G2) and (0.82 ±0.24) × 106 (G3) [AgNOR/cm2] respectively. In univariate analysis, but not in multivariate analysis, staging negatively correlated with better DFS and OS. sAgNOR, age of patients, grading and radicality of surgery were not associated with DFS or OS in either univariate or multivariate analysis.

Conclusions

sAgNOR analysis is not sufficient to precisely characterize cellular kinetics in serous ovarian tumors, and the analysis of sAgNOR, mAgNOR and pAgNOR should be performed commonly. The prognostic significance of sAgNOR in patients with serous ovarian cancer was not proven.  相似文献   

7.
8.
Molecular pathogenesis of high‐grade serous ovarian carcinoma (HG‐SOC) is poorly understood. Recent recognition of HG‐SOC precursor lesions, defined as serous tubal intraepithelial carcinoma (STIC) in fimbria, provides a new venue for the study of early genetic changes in HG‐SOC. Using microRNA profiling analysis, we found that miR‐182 expression was significantly higher in STIC than in matched normal Fallopian tube. Further study revealed that miR‐182 was significantly overexpressed in most HG‐SOC cases. To test whether miR‐182 plays a major role in early tumourigenesis of HG‐SOC, we overexpressed miR‐182 in immortalized ovarian surface, Fallopian tube secretory cells and malignant ovarian cell lines, and found that miR‐182 overexpression resulted in increased tumour transformation in vitro, and enhanced tumour invasiveness in vitro and metastasis in vivo. Mechanistically, we demonstrated that the oncogenic properties of miR‐182 in ovarian cancer were mediated in part by its impaired repair of DNA double‐strand breaks and negative regulation of breast cancer 1 (BRCA1) and metastasis suppressor 1 (MTSS1) expression as well as its positive regulation of the oncogene high‐mobility group AT‐hook 2 (HMGA2). Our findings suggest that miR‐182 dysregulation confers powerful oncogenic potential in the tumourigenesis of HG‐SOC. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.  相似文献   

9.
子宫颈病变中DEK和Ki-67蛋白过表达及其意义   总被引:6,自引:1,他引:6  
目的研究DEK和Ki-67基因蛋白检测对宫颈病变的临床病理学意义。方法20例正常宫颈上皮、83例宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)、87例宫颈鳞状上皮癌(squamous cell carcinoma,SCC)和32例宫颈腺癌(adenocarci-noma)共222例存档蜡块选自延边大学医院、延边妇幼保健院和延边肿瘤医院病理科。应用组织芯片和免疫组化方法检测DEK和Ki-67蛋白在上述病变组织中的表达。结果20例非肿瘤性的正常宫颈上皮组织标本中DEK和Ki-67蛋白表达阴性,而DEK蛋白和Ki-67蛋白的阳性表达率在SCC中分别为82.8%(72/87)和88.5%(77/87),在子宫颈腺癌标本中分别为84.4%(27/32)和93.8%(30/32),而在CIN-1标本中分别为54.3%(19/35)和57.1%(20/35),在CIN-2标本中分别为69.2%(18/26)和76.9%(20/26),在CIN-3标本中分别为77.3%(17/22)和81.8%(18/22)。DEK和Ki-67蛋白均与宫颈癌分级和分期不相关。结论DEK蛋白检测可以作为宫颈癌细胞的增殖指标之一,与Ki-67蛋白有着相似的阳性表达部位和表达率,可作为宫颈癌的早期诊断指标,并有望成为宫颈癌靶向治疗的新靶点。  相似文献   

10.
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。  相似文献   

11.
卵巢浆液性和黏液性肿瘤MUC1、MUC2的表达及其意义   总被引:2,自引:1,他引:1  
目的探讨卵巢浆液性和黏液性肿瘤中黏蛋白MUC1、MUC2的表达与临床病理特征的相关性。方法免疫组化S—P法检测90例卵巢浆液性和黏液性肿瘤的黏蛋白MUC1、MUC2的表达,并对其中50例恶性病例作生存分析。结果(1)交界性与恶性卵巢肿瘤中黏蛋白MUC1的表达阳性率明显高于良性肿瘤,差异有显著性(P〈0.001);黏蛋白MUC1与WHO病理分级、FIGO临床分期、大网膜转移显著相关(P〈0.05)。(2)黏蛋白MUC2与组织学类型、WHO病理分级相关(P〈0.05)。(3)黏蛋白MUC1与MUC2呈负相关(P〈0.05)。(4)对50例恶性浆液性和黏液性肿瘤进行的生存分析中,单因素分析显示:WHO病理分级、FIGO临床分期、大网膜转移、MUC1表达程度与预后相关(P〈0.05),而多因素分析中只有FIGO临床分期、MUC1表达程度具有独立的预后意义(P〈0.05),Kaplan—Meier生存曲线分析显示,Ⅲ、Ⅳ期较Ⅰ、Ⅱ期生存率差异有显著(P〈0.01),MUC1阳性组和阴性组生存率差异有显著性(P〈0.01)。结论黏蛋白MUC1、MUC2与恶性卵巢浆液性和黏液性肿瘤的浸润、转移相关,Ⅲ、Ⅳ期肿瘤、MUC1强表达可作为恶性卵巢浆液性和黏液性肿瘤预后不良的可行性指标。  相似文献   

12.
AIMS: It has been suggested that WT-1 is helpful in distinguishing a primary ovarian serous carcinoma (OSC) from a primary uterine serous carcinoma (USC). Since both neoplasms are often disseminated at diagnosis and since USC often spreads to the ovary and vice versa, it may be difficult to ascertain the primary site. This is important, since adjuvant therapies for OSC and USC may differ. WT-1 staining patterns also differ between OSC and ovarian endometrioid carcinoma and so it is possible that WT-1 may assist in the distinction of these two neoplasms, which is sometimes problematic, especially with poorly differentiated tumours. This study aims to document the value of WT-1 in these settings. Cases of ovarian borderline serous tumour, primary peritoneal serous carcinoma (PPSC) and uterine endometrioid carcinoma were also studied. METHODS AND RESULTS: Cases of OSC (n = 38), USC (n = 25) (in five of these cases there was also a component of endometrioid adenocarcinoma), ovarian endometrioid carcinoma (n = 13), uterine endometrioid carcinoma (n = 7), ovarian borderline serous tumour (n = 16) and PPSC (n = 6) were stained with WT-1. Cases were scored on a scale of 0-3, depending on the percentage of positive cells. The intensity of staining was scored as weak, moderate or strong. There was positive nuclear staining of 36 of 38 (94.7%) OSC with WT-1. In most OSC (68.4%), >50% of cells stained positively and staining was usually strong. Five of 25 (20%) USC were positive with only two cases exhibiting staining of >50% of cells. All primary ovarian and uterine endometrioid carcinomas were negative. All PPSC were positive, usually with diffuse strong immunoreactivity. Fourteen of 16 borderline serous tumours exhibited positivity with WT-1. CONCLUSIONS: WT-1 is useful in distinguishing OSC (characteristically diffuse strong nuclear positivity) from USC (characteristically negative). However, rarely OSC is negative and occasional cases of USC are positive. WT-1 may also be helpful in differentiating poorly differentiated OSC from poorly differentiated ovarian endometrioid carcinoma.  相似文献   

13.
14.
15.
There is debate as to whether peritoneal implants associated with serous borderline tumours/atypical proliferative serous tumours (SBT/APSTs) of the ovary are derived from the primary ovarian tumour or arise independently in the peritoneum. We analysed 57 SBT/APSTs from 45 patients with advanced‐stage disease identified from a nation‐wide tumour registry in Denmark. Mutational analysis for hotspots in KRAS and BRAF was successful in 55 APSTs and demonstrated KRAS mutations in 34 (61.8%) and BRAF mutations in eight (14.5%). Mutational analysis was successful in 56 peritoneal implants and revealed KRAS mutations in 34 (60.7%) and BRAF mutations in seven (12.5%). Mutational analysis could not be performed in two primary tumours and in nine implants, either because DNA amplification failed or because there was insufficient tissue for mutational analysis. For these specimens we performed VE1 immunohistochemistry, which was shown to be a specific and sensitive surrogate marker for a V600E BRAF mutation. VE1 staining was positive in one of two APSTs and seven of nine implants. Thus, among 63 implants for which mutation status was known (either by direct mutational analysis or by VE1 immunohistochemistry), 34 (53.9%) had KRAS mutations and 14 (22%) had BRAF mutations, of which identical KRAS mutations were found in 34 (91%) of 37 SBT/APST–implant pairs and identical BRAF mutations in 14 (100%) of 14 SBT/APST–implant pairs. Wild‐type KRAS and BRAF (at the loci investigated) were found in 11 (100%) of 11 SBT/APST–implant pairs. Overall concordance of KRAS and BRAF mutations was 95% in 59 of 62 SBT/APST–implant (non‐invasive and invasive) pairs (p < 0.00001). This study provides cogent evidence that the vast majority of peritoneal implants, non‐invasive and invasive, harbour the identical KRAS or BRAF mutations that are present in the associated SBT/APST, supporting the view that peritoneal implants are derived from the primary ovarian tumour. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.  相似文献   

16.
17.
Recently, oncogenic potential of the WT1 gene has been proposed in some human solid tumors and leukemias. Although previous studies have shown the frequent expression of the WT1 protein in ovarian serous adenocarcinomas (OSAs), its clinicopathologic significance is still unclear. We immunohistochemically examined the expression status of WT1 in 119 OSAs and analyzed the correlation of the intensity of WT1 immunoreactivity with the level of WT1 mRNA expression by quantitative real-time polymerase chain reaction, clinicopathologic variables, expression of p53, Bcl-2, and Ki-67 labeling index (LI). Of 119 OSAs, nuclear WT1 immunoreactivity was positive in 99 (83%), of which 44 (44%) and 55 (56%) exhibited high and low WT1 immunoreactivities, respectively. The quantitative WT1 mRNA levels were significantly correlated with the intensity of WT1 immunoreactivity (P < 0.05). In comparison with WT1-negative OSAs, the WT1-positive OSAs showed a higher grade (P = 0.007), advanced stage (P = 0.018), and higher Ki-67 LI (P < 0.001). Additionally, high WT1 immunoreactivity was correlated with a higher grade (P = 0.003), Ki-67 LI (P = 0.012), Bcl-2 expression (P = 0.003), and poorer patient outcome (5-year survival, 36.5 vs 63.8%, P = 0.008 by log-rank test). The WT1 protein may be an accelerator of the progression of OSA.  相似文献   

18.
High grade serous ovarian carcinoma (HGSC) without identifiable serous tubal intraepithelial carcinoma (STIC) within the fallopian tube (FT) occurs in approximately 50% of patients. The objective of this study was to use a multisite tumor sampling approach to study HGSC with and without STIC. RNAseq analysis of HGSC samples collected from multiple sites e.g. ovary, FT and peritoneum, revealed moderate levels of intrapatient heterogeneity in gene expression that could influence molecular profiles. Mixed-model ANOVA analysis of gene expression in tumor samples from patients with multiple tumor sites (n = 13) and patients with a single site tumor sample (n = 11) to compare HGSC-STIC to HGSC-NOSTIC identified neurotensin (NTS) as significantly higher (> two-fold change, False Discovery Rate (FDR) < 0.10) in HGSC-STIC. This data was validated using publicly available RNA-Seq datasets. Concordance between higher NTS gene expression and NTS peptide levels in HGSC-STIC samples was demonstrated by immunohistochemistry. To determine the role of NTS in HGSC, five ovarian cancer (OvCa) cell lines were screened for expression of NTS and its receptors, NTSR1 and NTSR3. Increased expression of NTS and NSTR1 was observed in several of the OvCa cells, whereas the NTSR3 receptor was lower in all OvCa cells, compared to immortalized FT epithelial cells. Treatment with NTSR1 inhibitor (SR48692) decreased cell proliferation, but increased cell migration in OvCa cells. The effects of SR48692 were receptor mediated, since transient RNAi knockdown of NTSR1 mimicked the migratory effects and knockdown of NTSR3 mimicked the anti-proliferative effects. Further, knockdown of NTSR1 or NTSR3 was associated with acquisition of distinct morphological phenotypes, epithelial or mesenchymal, respectively. Taken together, our results reveal a difference in a biologically active pathway between HGSC with and without STIC. Furthermore, we identify neurotensin signaling as an important pathway involved in cell proliferation and epithelial–mesenchymal transition in HGSC-STIC which warrants further study as a potential therapeutic target. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.  相似文献   

19.
目的探讨子宫浆液性癌(USC)及内膜上皮内癌(EIC)的组织病理学特点及鉴别诊断。方法回顾性分析13例USC和1例EIC的临床和病理学特点,并进行免疫组化染色观察p53、ER和PR在肿瘤细胞中的表达。结果患者年龄60~77岁(平均68岁),临床多表现为绝经后不规则阴道流血。随访10例,6例死亡,生存5~28个月(平均14个月);4例仍存活(11~36个月)。9例为单纯USC,4例混合有其他类型内膜腺癌成分。形态上,9例USC以有纤维血管轴心的宽乳头为主,被覆异型性明显的多角形或鞋钉样细胞,2例肿瘤大部分为纤细的乳头结构,1例以腺管状结构为主。2例表现为息肉表面的EIC,无间质浸润和腺体融合。3例USC的浸润成分以腺管结构为主。7例USC伴有EIC,其中2例宫颈内口、1例输卵管黏膜也可见上皮内癌改变。免疫表型:12例USC和所有EIC病变的非典型细胞对p53呈弥漫性强阳性反应,各有1例USC有ER、PR阳性表达。结论USC结构有一定的多样性,可以表现为分化好的腺管状结构。内膜活检标本中发现EIC改变时,提示可能有USC存在。应仔细检查绝经后妇女的内膜息肉以排除EIC改变。p53、ER、PR免疫组化染色有助于鉴别诊断。  相似文献   

20.
卵巢幼年型颗粒细胞瘤临床病理观察   总被引:1,自引:0,他引:1  
目的:探讨幼年型颗粒细胞瘤的临床病理学特点及诊断要点。方法:对2例幼年型颗粒细胞瘤进行临床资料、病理形态学及免疫组织化学观察,并结合文献对其诊断及鉴别诊断进行探讨。结果:2例镜下可见肿瘤细胞卵圆形或短梭形,胞质淡染,部分空泡状,成巢分布,呈多结节样生长,与周围卵巢组织有明显分界,局部区域有黏液样变性,血管丰富,部分细胞生长活跃,核分裂易见(5~7个/HPF),核沟不明显,未见Call-Exner小体。免疫组织化学染色结果:ER、PR、Vimentin和α-inhibit阳性,Ki-67增殖指数25%~40%不等。结论:卵巢幼年型颗粒细胞瘤是一种少见肿瘤,易与其他肿瘤混淆导致误诊,其临床病理特点应引起临床医师重视。  相似文献   

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