卵巢浆液性腺癌患者生存因素分析

目的 从卵巢癌患者机体免疫状态和肿瘤生物学行为两方面来探讨患者生存影响因素.方法 对获得随访的106例卵巢浆液性腺癌患者,按生存3年内和3年以上死亡分组进行统计分析.用流式细胞术(FCM)检测血清中IFN-γ、TNF-α、IL-2、IL-4、IL-5、IL-10表达水平和外周血淋巴细胞亚群CD3、CD4、CD8、CD4/CD8、CD56、CD19、CD25、CD44水平及临床病理资料.对照组检测细胞因子为51例女性职工体检健康者,检测淋巴细胞亚群及CD44表达为79例女性职工体检健康者.结果 生存组IFN-γ、IL-2、IL-4、IL-5高于对照组(P<0.01) ,IL-10高于对照组(P<0.05),IL-2/IL-4低于对照组(P<0.01);死亡组IFN-γ、IL-2、IL-4、IL-5、IL-10高于对照组(P<0.01) ,IL-2/IL-4低于对照组(P<0.01).死亡组IFN-γ高于生存组(P<0.05).外周血淋巴细胞亚群分析显示:生存组CD4/CD8、CD25高于对照组(P<0.01),CD56高于对照组(P<0.05),CD3、CD8低于对照组(P<0.01);死亡组CD25和CD44高于对照组(P<0.01),CD4/CD8高于对照组(P<0.05),CD3低于对照组(P<0.05).死亡组CD44高于生存组(P<0.05).卵巢浆液性腺癌患者的年龄,复发以及临床分期等因素与生存相关:生存组<50/≥50岁(22/23例)患者年轻多于死亡组(15/46例)(P<0.01);生存组复发/初发(15/30例)患者明显低于死亡组(35/26例)(P<0.01);生存组Ⅲ/Ⅳ期(42/3例)明显高于死亡组(46/15例)(P<0.05).结论 卵巢浆液性腺癌患者 IFN-γ和CD44水平升高、患者年龄≥50岁、肿瘤复发、临床分期晚是影响患者生存的重要因素.卵巢浆液性腺癌患者机体出现Th1/Th2失衡和不同程度的免疫机制紊乱.     

Multicolor karyotyping and clinicopathological analysis of three intravascular lymphoma cases.

Intravascular lymphoma (IVL) is a rare neoplastic disease characterized by the presence of large malignant lymphoid cells in small vessels. It is often diagnosed at autopsy. Clinical manifestations are typically neurologic and dermatologic. Karyotypic abnormalities have been described in a small number of cases and have revealed complex alterations in the majority of cases. We have identified three cases of IVL with varied clinicopathological findings. Karyotypic analysis was undertaken by standard G-banding and supplemented by multi-colored karyotyping (M-FISH) to decipher the chromosomal content of marker chromosomes and undefined additions. M-FISH clarified the chromosomal abnormalities in two cases and unveiled cryptic translocations der(10)t(10;22), der(17)t(17;22), and balanced t(11;14). Comparison with previously published karyotypes revealed prominent involvement of chromosomes 1, 3, 6, 11, 14, and 18, similar to the pattern of clonal evolution in other B-cell lymphomas. The most frequent alterations seen were -6 or 6q- and +18 or dup(18q), with a minimally deleted region located at 6q21-q23 and a commonly amplified region located at 18q13-q23, respectively. Few differences between the classical and Asian variant of this disease were apparent at the karyotypic level. Cytogenetic analysis of additional cases supplemented by multicolor karyotyping may help identify the full spectrum of genetic alterations associated with IVL and assist in the delineation of the critical mutations associated with initiation and progression of this disease.     

Multicolor spectral karyotyping of the L5178Y Tk+/- -3.7.2C mouse lymphoma cell line

The L5178Y/Tk+/- -3.7.2C mouse lymphoma cell line is characterized, at the cytogenetic level, by a karyotype involving both numerical and complex structural aberrations. While the karyotype is remarkably normal for a transformed cell line that has been in culture for almost half a century, there are a number of chromosomal alterations that because of their complexity cannot be fully characterized by routine or even high-resolution G-banding studies. Multicolor spectral karyotyping (SKY) was performed on the cell line in anticipation of identifying the previously unresolved chromosome aberrations and confirming interpretations previously identified by banding studies. New chromosome aberrations detected by SKY include numerical aberrations of chromosome 15, duplications of regions of chromosomes 4, 5, 12, and 18, and deletion of chromosome 14. Complex unbalanced translocations involved segments of chromosomes 6, 14, and 15. In total, the SKY technique was able to provide new refined designations on segments of eight different chromosome pairs (4, 5, 6, 9, 12, 14, 15, 18) and identified all three previously unidentified marker chromosomes. This analysis provides an updated standard reference for the karyotype of the L5178Y/Tk+/- -3.7.2C cell line used in the in vitro mouse lymphoma mutation assay.     

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。     

Cytologic findings in peritoneal fluids from patients with ovarian serous adenocarcinoma

The cytomorphologic observations of peritoneal fluid from seven patients with ovarian serous adenocarcinomas are presented. Some different cytologic findings, including smaller cell and nuclear size, larger relative nuclear area, fewer cells with large discrete cytoplasmic vacuoles and macronucleoli, more frequent multinucleolation, and larger closely packed clusters of cells, were shown in serous adenocarcinoma of the ovary as compared with those in other types of ovarian malignant neoplasms. Although the materials of nonserous tumors are too limited for a valid comparative study, prediction of histologic types by the peritoneal fluid cytology will be possible if the close cytomorphologic studies are performed.     

卵巢浆液性腺癌组织中TK1和Ki-67表达的意义

目的探讨细胞质胸苷激酶1(cytoplasmic thymidinekinas-1,TK1)、Ki-67在卵巢浆液性腺癌中表达的意义。方法回顾性研究55例经手术治疗的卵巢浆液性腺癌患者的临床病理资料,并运用免疫组化技术观察TK1、Ki-67在卵巢浆液性腺癌中的表达情况及与临床病理参数之间的意义。结果 TK1阳性表达定位于细胞质,阳性率为72.7%。TK1的表达与肿瘤的最大径、复发、pTNM分期、病理分级密切相关(P<0.05)。Ki-67阳性表达定位于细胞核,阳性率为80.0%,Ki-67的表达与肿瘤的复发、pTNM分期、病理分级有关(P<0.05)。Kappa检验显示TK1的表达与卵巢浆液性腺癌复发较一致(k=0.559,P=0.000),且判断复发比Ki-67更为优越。Kaplan-Meier检验显示pTNM分期、肿瘤复发、MDACC分级、Ki-67、TK1表达分别与预后有关(P<0.05)。COX回归多因素分析显示:肿瘤复发是影响卵巢浆液性腺癌患者的独立性预后因素。结论卵巢浆液性腺癌的复发影响患者的预后,TK1对判断卵巢浆液性腺癌是否有复发倾向具有参考价值,且优于Ki-67,初次手术后肿瘤组织免疫组化T...     

Two cases of peritoneal serous papillary adenocarcinoma.

Two cases of peritoneal papillary carcinoma are reported. The patient in the first case was a 71-year-old woman with symptoms of obstructive ileus. Laparotomy revealed a tumor in the omentum involving the transverse colon, and several small tumors in the peritoneum and pelvic wall. However, no primary site of the tumor was seen in the ovary, pancreas, or gastrointestinal tract. The patient in the second case was a 44-year-old woman with carcinomatous peritonitis. Postmortem examination revealed multiple tumors in the peritoneum, omentum, and pelvic wall. Tumors were also found in the cortex with mild invasion of the underlying parenchyma of the bilateral ovaries, although these lesions were thought to be metastatic. The histologic features of the tumor in both cases were those of tubulopapillary adenocarcinoma containing scattered psammoma bodies. The cells were positive with the PAS-D technique, but negative with alcian blue staining. In both cases, the serum levels of CA-125 were considerably elevated, and the tumor cells showed positivity for CA-125, S-100 protein, cytokeratin and EMA by immunohistochemistry. The present cases were most likely peritoneal serous papillary adenocarcinoma derived from extraovarian peritoneal mesothelium with müllerian potential, being different from the usual type of diffuse malignant mesothelioma.     

Characterization of chromosomal rearrangements in hematological diseases using spectral karyotyping.

Since chromosomal changes are used both as independent prognostic factors and for therapy design in hematological disorders, it is necessary to elucidate chromosomal changes as accurately as possible. We used spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) to further characterize chromosomal abnormalities in 35 patients with hematological disorders. SKY confirmed 149 aberrations, refined 117, and detected 11 hidden changes. Eighteen abnormalities were detected only by G-banding. Ten monosomies and two deletions described by G-banding were shown to be involved in translocations or ring chromosomes. These results demonstrate that SKY increases the accuracy of karyotype interpretation, which is important for proper diagnosis and management of hematological malignancies.     

Lectin binding to serous ovarian tumours.

Sections of normal ovarian surface epithelium, benign serous cystadenomas, borderline serous cystadenomas and serous cyst-adenocarcinomas were stained with a pattern of lectins (Con A, WGA, SBA, DBA, UEA I, PNA and RCA I) to determine the different glycoproteins and their cellular changes. The epithelial cells stained with Con A, WGA, UEA I and RCA, although the intensity of the staining was generally higher in the malignant tumours. PNA stained only the malignant cells of the cystadenocarcinoma and DBA only the benign epithelial cells. These findings show that ovarian epithelial cells contain different glycoconjugates and that malignant transformation is accompanied by changes in the composition of these glycoconjugates.     

Dickkopf-4血清蛋白在卵巢浆液性乳头状癌中的表达意义

目的研究Dickkopf-4(DKK-4)血清蛋白在卵巢癌中的表达及意义。方法收集2015年1月至2016年6月在中国医科大学附属盛京医院40例卵巢浆液性乳头状癌和40例正常自愿者血清。采用ELISA的方法检测DKK-4血清蛋白的表达情况,分析其与各临床病理参数的关系。结果 DKK-4蛋白在人卵巢浆液性乳头癌患者血清中的表达含量明显高于正常自愿者血清,其表达含量与卵巢浆液性乳头癌细胞分化程度明显呈正相关。结论 DKK-4蛋白可能参与卵巢浆液性乳头癌发病机制。     

Acute leukemia cytogenetics: an evaluation of combining G-band karyotyping with multi-color spectral karyotyping

We have, during a 12-month period, evaluated the adjuvant effect of combining G-band karyotyping and multi-color spectral karyotyping (SKY) in acute leukemia patients. Forty-four cases were evaluated; fewer cases than those routinely analyzed by G-band cytogenetics had mitoses left for SKY analysis. Of the 44 patients, 35 were acute myeloid leukemia (AML) and 9 acute lymphatic leukemia (ALL) cases. Twenty-seven of 35 AML and 7 of 9 ALL patients had an abnormal G-band karyotype. Thirteen of these 34 abnormal cases had a simple clonal chromosome aberration, and the remaining 21 cases had a complex karyotype. The SKY confirmed the simple karyotype in 11 and in 7 with a complex karyotype. In 13 of the cases with a complex karyotype, ambiguous structural aberrations were classified, in 6 of these, SKY disclosed cryptic translocations. Thus, SKY either extended or confirmed G-band karyotypes in 31 of 34 analyzed abnormal cases. Cases where SKY did not reveal the abnormal clone showed only few abnormal mitoses by G-banding (2/23, 2/25, and 4/27). Additional or confirmatory information was therefore obtained in 91% of analyzed cases, and SKY proved to be a valuable additional tool for hematologic cytogenetics.     

Heterotransplantation of ovarian serous adenocarcinoma with functioning stroma to nude mice. Disappearance of functioning stroma in transplanted tumor

Serous adenocarcinoma of the ovary with estrogen and alpha-fetoprotein (AFP) production was serially heterotransplanted into nude mice. The original tumor presented marked luteinization of stromal cells with elevated urine levels of estrogen before the operation. Estrogen levels reduced to the normal level shortly after the operation. Histologic features of the original tumor were basically retained in the transplanted tumor, but no luteinization of stromal cells was observed and serum estrogen levels in nude mice were elevated. Immunohistochemically, AFP was found to be positive in some tumor cells of transplanted tumor, but serum AFP levels were not elevated.     

Partial trisomy 17p detected by spectral karyotyping

We report the case of a child with partial trisomy of the short arm of chromosome 17, which was characterized by 24-color spectral karyotyping (SKY) and other fluorescence in situ hybridization (FISH) methods. The child had phenotypic features previously associated with trisomy 17p, including facial characteristics, developmental delay, postnatal growth retardation, single transverse crease, inguinal hernia, redundant neck skin folds, congenital heart defect, and club foot. This case illustrates the power of SKY for characterizing derivative/marker chromosomes in patients with rare cytogenetic syndromes.     

光谱染色体核型分析技术在胰腺癌研究中的应用

胰腺癌发病隐匿,仅20%左右的患者有手术机会,5年生存率不足5%,且发病率呈逐年上升趋势.寻找并确定可用于早期诊断的遗传学标记,是有效治疗胰腺癌的重要前提之一.     

Identification of an unusual marker chromosome by spectral karyotyping

We ascertained a newborn girl with multiple congenital anomalies including severe hypotonia, cardiovascular defects, hearing loss, central nervous system anomalies, and facial anomalies. The infant died at 12 days. Cytogenetic analysis showed a de novo supernumerary marker chromosome. Fluorescence in situ hybridization (FISH) with a combination of chromosome specific alpha-satellite probes and an all-human centromere probe failed to show hybridization to the marker, indicating that the marker chromosome lacked detectable alpha satellite sequences. Spectral karyotyping (SKY) was performed and showed that the marker was chromosome 15 in origin. This was confirmed by FISH with a 15q specific subtelomeric probe, which showed hybridization to both ends of the marker chromosome. Based on FISH information and G-banding pattern, the marker was determined to be an inverted duplication of 15q25-qter, leading to partial tetrasomy for chromosome 15. Although the marker chromosome lacked detectable centromeric alpha-satellite sequences, it seemed to have a functional centromere as it is mitotically stable. This observation is consistent with previous studies on acentric marker chromosomes, which suggested that the DNA sequence at the breakpoint could function similarly to alpha-satellite sequences once activated through marker formation. Am. J. Med. Genet. 80:368–372, 1998. © 1998 Wiley-Liss, Inc.     

Combined high grade sarcoma and serous ovarian neoplasm.

A case of an ovarian serous epithelial neoplasm of borderline type admixed with sarcomatous elements is reported. This combination seems to be extremely rare with only four cases previously reported. It may represent a type of collision tumour or the development of a sarcoma in a growth with borderline differentiation.     

miRNA-200c在IIIc期卵巢浆液性囊腺癌中的表达及其参与癌转移中的作用

研究miR-200c在IIIc期卵巢浆液性囊腺癌中的表达格局,探索其参与转移癌形成的相关机制。选取2010年1月至2013年12月上海交通大学医学院附属仁济医院妇科卵巢肿瘤组织标本(IIIc期卵巢浆液性囊腺癌40例(其中选择自身配对的原发灶40例、转移灶40例)、卵巢浆液性囊腺瘤30例为对照),采用real time-qPCR法检测miR-200c的表达;采用CCK8法、Transwell小室分别检测细胞过表达miR-200c后增殖、迁移和侵袭能力的改变;采用western blot法检测相关蛋白表达量。结果发现:(1)IIIc期卵巢浆液性囊腺癌转移灶肿瘤与原发灶肿瘤相比,miR-200c表达是升高的(490.37±78.32cf.157.46±17.21),P0.01;而且这两者均高于对照组(卵巢浆液性囊腺瘤)的表达(25.32±10.17),P0.01。SKOV3细胞过表达miRNA-200c后(2)细胞迁移能力降低(35.6±4.3cf.18.6±1.9),P0.05;侵袭能力降低(26.7±3.1cf.15.4±2.4)P0.05;但是增殖能力不改变。(3)在蛋白水平检测ZEB1蛋白表达下降(0.3023±0.0251cf.0.6753±0.0262)P0.05、E-cad蛋白表达升高(1.274±0.0331cf.0.6140±0.0460)P0.05、Vimentin蛋白表达降低(0.0957±0.0049cf.0.1767±0.0158)P0.05。可见,miR-200c在IIIc期卵巢浆液性囊腺癌组织样本中表达增高,检测miR-200c的表达格局对于临床上监测上皮性卵巢癌的临床进展和转移有重要意义;也为开拓过表达miR-200c作为卵巢癌治疗手段,提供了理论与实验依据。     

Sarcoma-like mural nodules in cystic serous ovarian tumours.

The morphology, immunohistochemistry, ultrastructure and natural history of sarcoma-like mural nodules in two serous cystic ovarian tumours are described.