Diagnosis of ovarian tumor by measuring tumor markers]

Values of CA125, CA19-9, TPA, CA72-4, BFP and LDH in sera were detected in 148 malignant ovarian tumors, 41 borderline malignant ovarian tumors, 71 benign ovarian tumors and 64 benign uterine diseases. A new cut-off value was determined by ROC graph for distinguishing malignant and borderline ovarian tumors from benign ovarian tumors. CA125 (cut off: 30 U/ml) was a highly sensitive marker for malignant and borderline malignant ovarian tumors, the value being 88.1% (52/59) and 81.8% (9/11), respectively. On the other hand, in 37 benign ovarian tumors, the positive rate was 21.6% and in 21 benign uterine diseases it was 52.4%. CA19-9 (cut off: 150 U/ml) was inferior to CA125, but it was an effective marker for mucinous ovarian tumors. TPA (cut off: 40 U/ml) was also a sensitive (84.7%, 50/59) marker of malignant ovarian tumors. CA72-4 (cut off: 4 U/ml) was a highly specific (87.0%, 60/69) marker of malignant ovarian tumors. Combination assays of CA125/CA19-9, CA125/TPA and CA125/CA72-4 were not effective. Usefulness of BFP for early malignant ovarian tumors was suggested. Seven cases of dysgerminoma showed extremely elevated LDH levels (1,248 +/- 886 IU/1/37 degrees C). Malignancy and histological type of ovarian tumors could be decided by combination assay of these tumor markers, before surgical operation.     

Tumor markers of ovarian cancer]

Many of the recently developed tumor markers are carbohydrate antigens, and are clinically useful for the diagnosis of ovarian cancers. These carbohydrate antigens can be classified into three major categories; core protein-related antigens (CP-RA), core of carbohydrate chain-related antigens (CSC-RA) and periphery of carbohydrate chain-related antigens (PSC-RA). CA125, CA602, and CA130 belong to CP-RA; CA602, CA72-4, and sialyl Tn to CSC-RA; and CA19-9 and sialyl LewisX (SLX), to PSC-RA. The positive rates of CP-RA in the sera of patients with ovarian epithelial cancers are usually very high except in the case of mucinous cystadenocarcinomas. Meanwhile, those of CSC-RA are higher than those of CP-RA in the sera of mucinous cystadenocarcinoma patients, and the false-positive rate of CSC-RA is lower than that of CP-RA in benign ovarian tumors. The diagnostic efficiency of PSC-RA is inferior to that of CA-RA and CSC-RA. Multi-variate analysis has revealed that the combination assay of these CP-RA and CSC-RA markers is the most effective among the carbohydrate antigen assays for the diagnosis of epithelial ovarian cancers. beta-core fragment (beta-CF), a fragment of the hCG beta-subunit missing its carboxyterminal peptide, is often detected in the urine of ovarian cancers, indicating that urine can be a good sample source for ovarian cancer detection.     

Review of tumor markers for ovarian cancer

Forty-two substances having been described as potential tumor markers for ovarian cancer are reviewed regarding sensitivity, specificity, and correlation with clinical course of disease. At present, there is no reliable marker for the primary diagnosis of the vast majority of ovarian cancers. Tumor markers may however serve as adjunctive tools in monitoring ovarian cancer patients after treatment.     

卵巢良性肿瘤组织和卵巢上皮癌组织基因表达差异的研究

目的 探讨卵巢上皮癌组织相关基因的差异表达.方法 采用含384条肿瘤相关基因的cDNA阵谱检测了卵巢上皮癌组织及卵巢良性肿瘤的基因谱,分析卵巢上皮癌组织相关基因的差异表达.结果 在384条候选基因中,与卵巢癌相关的差异表达基因36条,其中23条表达上调,13条表达下调.结论 cDNA阵谱技术是筛查卵巢癌相关基因的有效方法.     

Relationship between clinical signs and symptoms and nasopharyngeal flora in acute otitis media

Possible links between the clinical signs and symptoms of acute otitis media and the composition of the nasopharyngeal flora were investigated by reviewing the files of 1807 children enrolled in four randomised, multicentre trials. A standard protocol was used, nasopharyngeal samples were cultured, and signs and symptoms were recorded. Carriage of Haemophilus influenzae was associated positively with conjunctivitis (OR 4.83, 95% CI 3.76-6.20) and negatively with fever (OR 0.69, 95% CI 0.56-0.86). Carriage of pneumococci was associated positively with fever (OR 1.32, 95% CI 1.08-1.63) and negatively with conjunctivitis (OR 0.50, 95% CI 0.40-0.63).     

癌组织与癌栓上皮-间质转化相关标志物的对比研究

目的 通过对比上皮性原发癌、转移癌与其癌栓的组织形态学及E-cadherin和波形蛋白表达情况,从组织学水平探讨癌细胞在侵袭、转移过程中是否遵循上皮-间质转化(EMT)机制.方法 59例经病理诊断证实的原发性腺癌或原发性鳞状细胞癌及其淋巴结转移癌患者的68个石蜡组织标本,其中高分化癌组织13例,中分化癌11例,低分化癌30例,淋巴结转移癌14例,每例均有血管内或淋巴管内癌栓.挑选同一切面上同时具有癌组织(包含原发癌或淋巴结转移癌)及癌栓的蜡块进行HE染色观察形态及免疫组织化学(SP法)检测E-cadherin和波形蛋白表达.结果 癌组织与癌栓具有相似的形态学特征;54例原发性癌组织E-cadherin和波形蛋白阳性分别为50和23例,其癌栓阳性分别为51和22例,经统计学分析两者的E-cadherin和波形蛋白表达差异无统计学意义(P =0.804,P=0.842);14例淋巴结转移性癌组织E-cadherin和波形蛋白阳性分别为12和6例,其癌栓E-cadherin和波形蛋白阳性分别为12和7例,两者的E-cadherin和波形蛋白表达差异无统计学意义(P=0.084,P=0.878);癌组织和癌栓的E-cadherin和波形蛋白表达差异无统计学意义(P=0.410,P=0.824);癌栓部分癌细胞高表达E-cadherin而波形蛋白缺失,部分癌细胞高表达波形蛋白而E-cadherin缺失.结论 原发癌及其淋巴结转移癌、癌栓三者EMT特征无显著差异;癌栓细胞既有EMT细胞也有非EMT细胞,它们在肿瘤转移过程中的作用尚待进一步研究.     

Comparison between clinical significance of serum CXCL-8 and classical tumor markers in oesophageal cancer (OC) patients

C-X-C motif chemokine 8 (CXCL-8), known as interleukin-8, is a pro-inflammatory cytokine which acts as a chemotactic factor, mainly for leukocytes. CXCL-8 is produced by malignant cells, and therefore it can stimulate the growth and progression of various neoplasms, including oesophageal cancer (OC). The aim of the current study was to measure serum concentrations of chemokine CXCL-8 in OC patients and establish whether this protein might be considered a potential candidate for a tumor marker in the diagnosis and progression of OC. The study included 50 OC subjects (32 patients with squamous cell carcinoma of oesophagus—OSCC, 18 patients with adenocarcinoma—OAC) and 26 healthy volunteers. Serum CXCL-8 concentrations were measured using immunoenzymatic assay (ELISA). CRP levels were determined by immunoturbidimetric method, while classical tumor marker levels were measured using chemiluminescent immunoassay. CXCL-8 concentrations were significantly higher in OC patients compared to healthy controls. We demonstrated significant differences between CXCL-8 concentrations and depth of tumor invasion (T factor) in OC patients and OSCC subgroup. In addition, CXCL-8 levels were found to correlate positively with T factor and CRP concentrations. The diagnostic sensitivity, negative predictive value and the area under ROC curve (AUC) of CXCL-8 were higher than those of classical tumor markers. Our findings suggest the potential usefulness of CXCL-8 in the diagnosis and progression of OC. However, due to the non-specific nature of this chemokine, further research is needed to clarify the usefulness of CXCL-8 as a tumor marker of OC.

     

The relationship between tumor size and stage in early versus advanced ovarian cancer

Background

Ovarian cancer has a different prognosis between early (I and II) and advanced stage (III and IV). The mechanism of disease progression is unknown, but patients with advanced disease may have a higher propensity for seeding of the abdominal cavity early in the disease process than those with early stage. Theoretically if this is so, then patients with advanced stage should have smaller sized tumors than patients with early stage.

Methods

This was a retrospective chart review of patients in the tumor registry in 2003–2006. Patients had epithelial ovarian cancer, other cell types were excluded. Only cases with documentation of surgical and pathologic staging and measured dimensions on pathologic specimen were included. Patient stage and all available dimensions measured on diseased ovaries were recorded. The dimensions for each patient were averaged into a single dimension for that patient, and then these measurements were totaled and averaged.

Results

There were 110 patients analyzed: 85 with advanced disease, 25 with early stage. The average measurement was 4.8 cm in advanced disease, and was 10.7 cm in early stage disease. This difference was statistically significant (p < 0.001).

Conclusions

Overall, patients with early stage ovarian cancer have diseased ovaries that are more than twice as large as those found in advanced disease. This finding supports the fact that early versus advanced ovarian cancer are 2 separate disease processes. Early stage grows locally and does not disseminate, and advanced stage disseminates while the tumor is still relatively small. Theoretically there may be a factor that separates these 2 into different diseases, where advanced disease patients have a substance produced by their tumor that allows for early dissemination, and early stage lacks this substance and only grows locally. Basic science research comparing the tissue microarrays of early versus advanced stage disease may be able to identify this difference. If the difference is found, perhaps therapy can be targeted against this difference, and screening tests for advanced ovarian cancer can be improved.     

促超排卵时相与临床妊娠率关系的初步研究

目的研究IVF-ET及ICSI过程中控制性促超排卵的时相与临床妊娠率之间的关系,及其对胚胎质量、子宫内膜状态的影响.方法选取本院生殖中心的112个IVF-ET及ICSI周期,包括黄体中期长方案、短方案、超短方案等模拟自然周期的促超排卵方案,研究促性腺激素(Gn)启动日、Gn使用天数、hCG日等时相性因素与临床妊娠率之间的关系,并分析Cn使用天数对胚胎质量及hCG日对子宫内膜状态的影响.结果Gn启动日与临床妊娠率无显著相关性,Gn使用天数为9～10d或hCG日在月经第12～14d的临床妊娠率显著升高(P分别＜0.01及=0.001),而且,Gn使用天数为9～10d所获得的胚胎质量提高(P＜0.05).结论IVF-ET及ICSI的临床妊娠率与促超排卵的时相相关,适当的Gn使用天数可以提高胚胎质量、适宜的hCG日则通过同步胚胎与子宫内膜的发育发挥作用.     

Relationship between the expression of various markers and prognostic factors in breast cancer

The immunohistochemical detection of six markers of breast cancer has been compared in the present study with known prognostic factors of the disease to establish locally a standard panel of markers for the management of breast cancer. Sections of tissue of 114 consecutive breast cancer cases were studied immunohistochemically, using antibodies against oestrogen receptor (ER), progesterone receptor (PR), androgen receptor, c-erbB2, cathepsin D, and cyclin D. Marker labelling was graded as recommended in the literature. Using the chi(2)-test, relationships were determined between marker labelling and histological type of cancer, tumour grade, tumour size, axillary lymph node status and age of patient. A p value below 0.05 was considered significant. A positive relationship was found between ER and PR and lower grades of cancer, and a negative relationship was found with medullary and atypical medullary carcinoma. The four other markers showed no relationship with grade or type of cancer. All markers showed no significant relationship with size of tumour, presence of axillary node metastasis or age of patient. There was positive correlation between c-erbB2 and cathepsin D. Our study confirms the association between ER and PR and histological type and grade of breast cancer, both known parameters of good prognosis. We found no consistent relationship between the other four markers and prognostic factors studied, other than the suggestion that c-erbB2 and cathepsin D may be useful markers for poor prognosis and can be usefully applied locally, especially in the light of the current availability of trastuzumab (Herceptin) for management of c-erbB2-positive cases. We found no relationship between the markers and tumour size, axillary lymph node status or age.     

甲状腺髓样癌中CD133和CD44的表达及意义

目的 探讨肿瘤干细胞(cancer stem cells,CSC)标志物CD133及CD44在甲状腺髓样癌(medullary thyroid cancer,MTC)组织中的表达及临床病理意义.方法 采用免疫组化SP法检测51例MTC组织中CD133和CD44的表达.结果 (1)CD133蛋白在MTC伴有包膜浸润组的阳性率(76.2％,16/21)明显高于无包膜浸润组(43.3％,13/30);CD133蛋白在MTC病灶直径≥1 cm组的阳性率(64.4％,29/45)显著高于病灶直径＜1 cm组(0,0/6),差异均有统计学意义(P均＜0.05).(2)CD44蛋白在MTC伴有包膜浸润组的阳性率(66.7％,14/21)明显高于无包膜浸润组(20％,6/30),差异有统计学意义(P＜0.01).(3) MTC中CD133和CD44蛋白的表达与患者年龄、性别、是否散发、甲状腺受累范围、淋巴结转移、远处脏器转移、TNM分期均无关(P＞0.05).(4)CD133与CD44共表达与MTC包膜浸润密切相关(P＜0.01).结论 MTC中存在CSC,其与肿瘤的浸润生长及恶性增殖相关,可考虑将CD133及CD44作为MTC临床评价肿瘤生物学行为的指标.二者可能存在互相调节的机制,共表达在MTC的恶性进展中发挥作用.     

Relationship between tumor grade and computed architectural complexity in breast cancer specimens

Breast cancer is the leading form of cancer diagnosed in women, and the second leading cause of cancer mortality in this group. A commonly accepted grading system for breast cancer that has proven useful for guiding treatment strategy is the modified Bloom-Richardson system. However, this system is subject to interobserver variability, which can affect patient management and outcome. Hence, there is a need for an independent objective and reproducible breast cancer-grading tool to reduce interobserver variability. In this work, we hypothesized that architectural complexity of epithelial structures increases with decreasing differentiation in ductal carcinoma of the breast. To test this hypothesis, we explored the potential of a computer-based approach using fractal image analysis to quantitatively measure the complexity of breast histology specimens and investigate the relationship between increasing fractal dimension and tumor grade. More specifically, we developed an optimal staining and computational technique to compute the fractal dimensions of breast sections of grades 1, 2, and 3 tumors, assigned by a breast cancer pathologist, and compared the mean fractal dimensions between the tumor grades. We found that significant differences (P < .0005) exist between the mean fractal dimensions corresponding to the 3 tumor grades, and that the mean fractal dimension increases with increasing tumor grade. These results indicate that breast tumor differentiation can be characterized by the degree of architectural complexity of epithelial structures. They also indicate that fractal dimension has potential as an objective, reproducible, and automated measure of architectural complexity that may help reduce interobserver variability in grading.     

卵巢癌患者调节性T细胞比率和肿瘤标志物CA125、CA19-9测定及临床意义

目的 探讨卵巢癌患者、卵巢良性疾病及健康成人女性调节性T细胞（Tregs）和肿瘤标志物CA125、CA19-9水平的差异,并将其与临床病理因素及预后进行相关分析。 方法 选择2016年10月~2017年10月承德医学院附属医院妇科收治的经病理确诊的卵巢癌患者43例,设为恶性组,另选择同期医院收治的卵巢良性疾病患者55例作为良性组,健康体检妇女50例作为对照组。比较3组患者Tregs和肿瘤标志物CA125、CA19 9在卵巢癌患者中的表达水平,分析其与临床病理因素及预后的关系。 结果 恶性组和良性组Tregs比例、CA125和CA19-9水平均高于对照组,恶性组Tregs比例、CA125和CA19-9水平高于良性组（P<0.05）。CA125、CA19-9、Tregs水平与患者的年龄差异无显著性（P>0.05）;CA125水平与卵巢癌患者的淋巴结是否转移、肿瘤分期和组织学类型均有关;Tregs表达水平与卵巢癌患者的淋巴结是否转移和肿瘤分期均相关,CA19-9水平只与肿瘤分期相关（P<0.05）。随访12个月后,Tregs-low组中位生存时间高于Tregs-high组（P<0.05）。卵巢癌中Tregs数与CA125存在显著正相关性（P<0.05）,而与CA19-9不具有相关性（P>0.05）。 结论 Tregs、CA125和CA19-9均可有望成为卵巢癌临床诊断、治疗和预后的指标。     

Hematopoietic cytokines as tumor markers in gynecological malignancies. A multivariate analysis in epithelial ovarian cancer patients

We investigated plasma levels of selected hematopoietic cytokines: stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and macrophage colony-stimulating factor (M-CSF) and the tumor marker cancer antigen (CA 125) in epithelial ovarian cancer patients as compared with control groups: benign ovarian tumor patients (cysts) and healthy subjects. Cytokine levels were determined by enzyme-linked immunosorbent assay, CA 125 – using the chemiluminescent microparticle immunoassay method. Our results have demonstrated significant differences in the concentrations of M-CSF, G-CSF, SCF (with the exception of GM-CSF), and CA 125 between the groups of ovarian cancer patients, cysts patients, and the healthy controls. When compared with CA 125, M-CSF has equal or higher values of diagnostic sensitivity and specificity. The M-CSF area under the receiver-operating characteristic curve (AUC) was the largest from all the cytokines tested and slightly lower than the AUC of CA 125. These findings suggest the usefulness of M-CSF in diagnosing ovarian cancer, especially when discriminating between cancer and non-carcinoma lesions.     

Vaccine-based clinical trials in ovarian cancer

Ovarian cancer vaccines are one of the new treatment strategies under investigation in epithelial ovarian cancer. This article discusses the results of different immunization strategies, points out potential pitfalls in study designs and provides possible solutions for augmentation of clinical efficacy. Most ovarian cancer vaccines have not yet evolved beyond Phase I/II studies, which do not primarily evaluate clinical efficacy. Although different approaches of antigen-specific immunization generally result in antigen-specific immune responses, clinical benefit is not consistently observed. Based on the currently available results, we emphasize the necessity of multimodal treatment of ovarian cancer, combining classical cytoreductive surgery, (neo)adjuvant chemotherapy, immunotherapy and/or targeted therapy.     

Relationship between serologic response and clinical symptoms in children with enterovirus 71-infected hand-foot-mouth disease

This study aimed to explore the correlation between clinical symptoms, including rash and fever, and serum antibody reaction to enterovirus 71 (EV71) infection in children hospitalized due to hand-foot-mouth disease (HFMD). From May 2014 to July 2014, a total of 547 children hospitalized due to HFMD in Children’s Hospital of Fudan University were enrolled retrospectively. RNA levels of EV71 and CA16 in fecal, serum, and cerebrospinal fluid specimens were measured using quantitative real-time RT-PCR, and EV71-IgM antibody in the serum was detected using immune colloidal gold assays. Of the 547 fecal specimens, 296 were EV71 RNA positive, 109 were CA16 RNA positive, and 8 were positive for both EV71 RNA and CA16 RNA. The total positive rate for either EV71 or CA16 in feces was 72.58% (397/547). Additionally, 544 serum specimens were collected, and 409 were EV71-IgM positive (75.18%). The duration of rash and fever was found to be correlated to the positive rate of serum EV71-IgM, and the positive rate of serum EV71-IgM plus EV71 RNA in feces. The positive rates of serum EV71-IgM and serum EV71-IgM plus EV71 RNA in fecal collected at day 3 of fever were 79.7% and 52.8%, respectively. In conclusion, EV71 and CA16 were found to be the major pathogens responsible for the epidemics of HFMD in children during May to July 2014 in Shanghai, China. There is a close relationship between the positive rate of serum EV71-IgM and the duration of fever and rash.     

Relationship between premenstrual symptoms and general well-being

Data on the general well-being and premenstrual symptoms of military wives were collected on two occasions one year apart. The women's general well-being and premenstrual symptoms were highly correlated on both occasions, but an even higher correlation was found between the presence of premenstrual symptoms at time 1 and the presence of premenstrual symptoms at time 2. Further analyses revealed that women with higher scores on general well-being and premenstrual symptoms were older and reported fewer cognitive depressive symptoms than women with lower scores on general well-being and premenstrual symptoms. At the one-year follow-up, the women with lower scores on general well-being who complained of premenstrual symptoms were more depressed than those who did not.