Clinicopathological significance of DEK overexpression in serous ovarian tumors

To investigate the significance of DEK protein expression in ovarian lesions, a total of 113 ovarian serous tumors, including 62 serous cystadenocarcinomas and 19 serous borderline tumors, were studied on immunohistochemistry. For comparison, 32 benign serous tumors, including 12 serous papillary cystadenomas, 10 serous cystadenomas, and 10 serous surface papillomas, were also included. DEK was positive in 93.5% of serous cystadenocarcinomas (58/62), 63.2% of serous borderline tumors (12/19), and weakly positive in 15.6% of benign serous tumors (5/32). The strong positive signal was detected only in serous adenocarcinomas (80.6%, 50/62) and borderline tumors (21.1%, 4/19), but no serous benign tumors were strongly positive (0%, 0/32). Meanwhile, the strong positivity rate of DEK protein was significantly higher in grade 2 and grade 3 than in grade 1 ovarian cancers ( P < 0.05), but there was no significant association between DEK protein expression level and International Federation of Gynecology and Obstetrics (FIGO) stage of serous ovarian adenocarcinoma ( P > 0.05). In summary, DEK plays an important role in the progression of ovarian serous cancers. The detection of DEK protein expression should be useful for the diagnosis and prognosis of ovarian serous cancers, and DEK might be a useful molecular target for ovarian cancer therapy.     

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.     

Advances in serous tubal intraepithelial carcinoma: correlation with high grade serous carcinoma and ovarian carcinogenesis

Early serous carcinoma in fallopian tube or serous tubal intraepithelial carcinoma (STIC), an early lesion limited to the epithelium of the fallopian tube and firstly identified from specimen obtained by prophylactic salpingo-oophorectomy, has provided insight into pelvic high grade serous carcinoma (HGSC). Increasing evidence indicates that STIC is a likely precursor for HGSC and several studies have focused on this lesion and its clinical significance. This review addresses recent advances in recognizing STIC and its correlation with HGSC and ovarian carcinogenesis. It also describes evidence regarding the fallopian tube as a source of some HGSCs, the protocol for optimizing histological evaluation of the tubes, the spectrum of tubal lesions from benign to noninvasive carcinoma, changes in diagnostic criteria from purely morphologic characteristics to a combination of morphologic features and molecular biomarkers, and new studies about potential biomarkers. However, the direct evidence regarding STIC as the precursor of HGSC is still tantalizing due to other possibilities that may also explain the origin of pelvic HGSC. Further molecular genetic studies are required to address this important question.     

HLA-DR抗原在慢性乙型肝炎和肝细胞癌中的表达及其意义

目的　探讨HLA DR抗原在慢性乙型肝炎和肝细胞癌 (HCC)中的表达及其意义。方法采用免疫组化技术对 2 0例正常肝组织、36例慢性乙型肝炎和 44例HCC中HLA DR抗原的表达进行检测。结果　正常肝组织中肝细胞未见HLA DR抗原表达。慢性乙型肝炎肝细胞HLA DR抗原表达阳性率为 2 7.8% ,其中 ,中度和重度肝炎HLA DR抗原阳性率明显高于轻度肝炎 (阳性率分别为 37.5 %和 2 0 % ,χ2 =13.6 ,P <0 .0 1)。HCC中肿瘤细胞HLA DR抗原表达阳性率为 43.2 %。HLA DR抗原表达与癌周淋巴细胞浸润 (χ2 =0 .5 1,P >0 .0 5 )和转移 (χ2 =2 .9,P >0 .0 5 )无关 ,但与癌组织分化程度有关 (χ2 =4.9,P <0 .0 5 )。结论　HLA DR抗原的异常表达在慢性乙型肝炎免疫损伤、免疫保护和HCC发生、发展中起重要作用     

Incidence of P53 and K-ras alterations in ovarian mucinous and serous tumors

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.     

Mutational analysis of BRAF and KRAS in ovarian serous borderline (atypical proliferative) tumours and associated peritoneal implants

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.     

Ezrin在浆液性卵巢癌中的表达及临床意义

目的通过检测Ezrin在正常卵巢上皮和浆液性卵巢癌组织中的差异表达,探讨其对浆液性卵巢癌发生发展的影响。方法收取浆液性卵巢癌冷冻组织40例,正常卵巢上皮27例,提取总RNA,采用Real-time PCR技术检测Ezrin mRNA在两组样本中的表达差异;选取有完整临床病理资料的浆液性卵巢癌石蜡包埋组织134例,以及27例非卵巢癌病例的卵巢上皮组织,通过免疫组织化学染色检测两组样本中Ezrin蛋白质的表达差异,并应用SPSS 20.0软件分析其与临床病理的相关性。结果 Ezrin mRNA在新鲜卵巢癌组织中的表达显著低于正常卵巢上皮组织(P0.05)。Ezrin蛋白在石蜡包埋卵巢癌组织中也相应降低(P0.05)。Ezrin蛋白质表达水平与年龄、手术满意程度及化疗敏感程度无相关性,与细胞分化、病理分期及大网膜转移显著相关,(P0.05)。Ezrin表达水平高的浆液性卵巢癌病例的无进展生存期(PFS)值和总生存期(OS)值都明显高于表达水平低的病例(P0.05)。但Ezrin并不能作为浆液性卵巢癌的独立预后因素。结论 Ezrin的表达下调与浆液性卵巢癌的发生发展、转移等病理过程相关,其可以作为临床预后的潜在指标。     

Cystadenoma of spermatic cord resembling ovarian serous epithelial tumour of low malignant potential: immunohistochemical study suggesting Müllerian differentiation

A cystic lesion of the spermatic cord resembling an ovarian serous epithelial tumour of low malignant potential or borderline malignancy is reported. Immunohistochemical staining and electronmicroscropic examination suggested epithelial rather than mesothelial differentiation of the cyst lining cells. There was strong positive immunohistochemical staining of cyst lining cells for CA 125, providing evidence for Müllerian differentiation. A flow cytometric analysis of nuclear DNA content revealed a diploid profile.     

癌灶CD4~+CD25~+和CD8~+ T细胞亚群与卵巢浆液性癌患者生存期相关

检测卵巢浆液性癌患者癌组织中CD4+CD25+及CD8+T细胞的数目,探讨其两种T细胞介导的免疫功能对疾病发展及预后的影响。免疫组织化学双标及单标的染色方法检测41例卵巢浆液性癌患者手术切除癌组织标本中CD4+CD25+和CD8+T细胞的数目。结果显示,癌灶中CD4+CD25+T淋巴细胞为(19.95±11.50)个/10HPF,CD8+T淋巴细胞为(43.46±16.69)个/10HPF。生存分析发现高CD4+CD25+T细胞组患者总生存期较低CD4+CD25+T细胞组缩短,差异有显著性(P<0.05);而高CD8+T细胞组患者总生存期与低CD8+T细胞组相比延长,且差异有显著性(P<0.05),此外两种T细胞数目与患者年龄、病理分级、临床分期、腹水细胞学及淋巴结转移等临床病理因素均无关(P>0.05)。结果表明,卵巢浆液性癌中高CD4+CD25+T细胞提示患者预后不良,可能与CD4+CD25+T细胞介导的免疫抑制导致肿瘤免疫逃逸有关;癌组织中高CD8+T细胞提示患者预后较好,两种T细胞对卵巢浆液性癌预后的评估有重要的价值,同时可以通过阻断CD4+CD25+T细胞的免疫抑制作用改善卵巢浆液性癌患者的预后,为卵巢癌治疗提供靶目标。     

Detection of M2 macrophages and colony-stimulating factor 1 expression in serous and mucinous ovarian epithelial tumors

Tumor-associated macrophages (TAM) are known to possess the immunosuppressive M2 macrophage phenotype. They contribute to tumor growth, invasion, and metastasis by producing various mediators. Macrophages, especially M2 polarized macrophages, preferentially express CD163 and CD204, but few studies have investigated macrophage phenotypes in human ovarian tumors. The purpose of the present study was therefore to present results on macrophage differentiation in human ovarian serous and mucinous epithelial tumors. The method focused on immunostaining of paraffin-embedded tumor samples. Almost all macrophages infiltrating tumor tissues expressed CD163 and CD204, indicating the phenotypic shift toward M2 macrophage. The numbers of CD68-positive macrophages as well as of CD163- and CD204-positive macrophages in borderline and malignant tumors were significantly higher than in benign tumors. They correlated well with histological gradient of malignancy. Macrophage colony-stimulating factor (also known as colony-stimulating factor; CSF-1), which is one of the cytokines considered to induce TAM to polarize toward an M2 phenotype, was then evaluated. CSF-1 expression in malignant tumor cells was significantly higher than that in benign tumor cells and correlated with histological malignancy. These results suggest that CSF-1 derived from tumor tissues induces macrophages to shift toward the M2 phenotype, which is considered to promote tumor growth.     

卵巢浆液性癌中Netrin-1的表达及其临床意义

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。     

SIRT2在浆液性卵巢癌细胞系中的表达及其对增殖、迁移和侵袭的影响

目的:研究SIRT2在卵巢表层上皮(ovarian surface epithelium,OSE)及浆液性卵巢癌(serous ovarian carcinoma,SOC)细胞系中的表达情况并从细胞增殖、迁移和侵袭这3个方面探讨SIRT2对SOC恶性生物学行为的影响。方法:运用Western blot技术检测OSE和SOC细胞系中SIRT2蛋白的表达水平;设计靶向SIRT2的siRNA,构建SIRT2过表达载体,分别瞬时转染OSE细胞系HOSEpi C和SOC细胞系HO8910,平板克隆形成实验和CCK-8实验研究SIRT2对细胞生长的影响;细胞划痕实验考察SIRT2在SOC细胞迁移中的作用;Transwell实验研究SIRT2对SOC细胞侵袭能力的影响。结果:5株SOC细胞系中SIRT2的表达水平显著低于OSE细胞系。在HOSEpi C细胞中沉默SIRT2,细胞克隆形成数增多,细胞活力增强。相反,在HO8910细胞中过表达SIRT2,细胞克隆形成数减少,细胞活力降低。沉默SIRT2促进HOSEpi C细胞的迁移,而过表达SIRT2则抑制HO8910细胞的迁移。沉默SIRT2的HOSEpi C细胞侵袭能力明显增加,而过表达SIRT2的HO8910细胞侵袭能力则显著降低。结论:SIRT2在SOC细胞中表达显著下调。SIRT2在OSE细胞中是肿瘤抑制蛋白,抑制细胞增殖、迁移和侵袭。     

Ovarian serous cystadenoma with mural nodules of genital rhabdomyoma

We present an extremely rare case of ovarian serous cystadenoma with mural nodules of rhabdomyoma. The patient, a 48-year-old woman, was admitted to our hospital with left lower abdominal pain and vaginal bleeding. A unilocular cystic tumor, measuring 13 x 10 x 10 cm, was found in her left ovary and was removed. The tumor contained clear serous fluid, approximately 600 mL, and 2 mural nodules, up to 7.5 x 5.5 x 4.5 cm. The internal cystic wall was thin for the most part and lined with ciliated cuboidal epithelium without any malignant feature. The mural part was composed of mainly more mature muscle fibers with easily discernible cross-striations, set in abundant myxoid to fibromyxoid stroma, similar to clinical and microscopic manifestations of genital rhabdomyomas reported in other sites. Because extracardiac rhabdomyoma has never been described occurring in the ovary, especially arising in serous cystadenoma, to our knowledge, this is the first case reported in the English literature.     

Ki-67抗原和Survivin基因在上皮性卵巢癌中表达增强且相关

目的探讨卵巢上皮性肿瘤中Ki-67抗原和Survivin的表达及其相关性。方法用免疫组织化学技术二步法检测47例上皮性卵巢癌和24例良性上皮性卵巢肿瘤中Ki-67抗原和Survivin的表达。结果Ki-67阳性染色位于细胞核,良性肿瘤中Ki-67指数为0.17±0.20,显著低于恶性的19.59±16.48(P<0.01)。Survivin在良性卵巢肿瘤中的表达率为33.33%,显著低于恶性的70.21%(P<0.01)。Ki-67和Survivin在上皮性卵巢癌中的表达均与组织学类型无关,而与临床分期及病理学分级密切相关(P<0.01)。Ki-67和Survivin的表达有相关性。结论Ki-67和Sur-vivin基因在卵巢癌中表达增强且相关。     

WT-1 assists in distinguishing ovarian from uterine serous carcinoma and in distinguishing between serous and endometrioid ovarian carcinoma

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.     

基质金属蛋白酶-7在卵巢浆液性肿瘤中的表达

目的：探讨MMP－7在卵巢浆液性肿瘤中的表达情况。方法：采用免疫组化SP法对6例正常卵巢、12例卵巢浆液性囊腺瘤、6例交界性囊腺瘤及22例卵巢浆液性囊腺癌MMP－7的表达进行了研究。结果：正常卵巢不表达MMP－7。大部分卵巢浆液性肿瘤的胞浆及间质中都有MMP－7的阳性表达。MMP－7的卵巢良性，恶性及交界性浆液性肿瘤胞浆中的表达无明显差异；而在肿瘤间质中，恶性及交界性卵巢浆液性肿瘤中的表达远高于良性肿瘤（P＜0．05）。在交界性及恶性浆液性卵巢肿瘤中，部分肿瘤细胞的细胞核中也有MMP－7的表达，为国内外首次报道。结论：MMP－7可能在卵巢浆液性肿瘤的进展中发挥重要作用。