p53蛋白表达与上皮性卵巢癌恶性程度及预后的关系研究

目的：研究p53蛋白表达与上皮性卵巢癌恶性程度及预后的关系。方法：采用免疫组化SP法测定26例上皮性卵巢癌中p53蛋白表达。结果：p53蛋白在黏液性、浆液性、内膜样卵巢癌中的表达率（88.9%、75%、100%）无明显差异（P〉0.05）;三种卵巢癌的复发率分别为33.3%、12.5%、0,以黏液性癌最高,三者之间有显著差异（P〈0.05）;p53蛋白在淋巴结转移卵巢癌患者中均为高表达（100%）,与无淋巴结转移者（68.75%）相比差异明显（P〈0.05）;另外,淋巴结转移卵巢癌患者的复发率（40%）较无淋巴结转移患者（6.25%）明显增高（P〈0.05）。p53蛋白在I-II期和III-IV期卵巢癌的高表达（50%、100%）具有显著差异（P〈0.01）,不同期别卵巢癌复发的几率也存在显著差异,其中I-II期复发率为0,III-IV期复发率为31.25%。结论：p53蛋白的高表达与上皮性卵巢癌的恶性程度及预后有着密切的关系。     

Hepsin在卵巢癌组织中表达与临床病理意义

目的 探讨Hepsin蛋白表达与卵巢癌临床病理相关性。方法 采用免疫组化方法检测正常卵巢20例、卵巢良性肿瘤25例和卵巢癌139例中Hepsin蛋白表达情况。采用统计学方法分析Hepsin蛋白表达与临床病理的关系。结果 所有卵巢癌样本中有90例(64.7%)Hepsin高表达,正常卵巢和卵巢良性肿瘤均未见明显表达或弱表达。FIGO分期越晚,Hepsin蛋白表达程度越高;组织分化程度与Hepsin蛋白表达程度呈正相关,即组织分化越差,Hepsin蛋白表达量越高。结论 Hepsin蛋白的表达与卵巢癌上皮癌的临床分期和组织分化程度密切相关,Hepsin蛋白表达与临床分期呈正比,而与组织分化程度成反比。Hepsin蛋白异常表达可能是促进卵巢癌发生发展的重要机制。     

Chemosensitivity and p53-dependent apoptosis in epithelial ovarian carcinoma.

BACKGROUND: Although p53 gene mutation frequently is observed in ovarian carcinoma, the function of the p53 gene in chemosensitivity has not been defined conclusively. The objective of the current study was to elucidate the relation between chemotherapy-induced apoptosis through the p53 pathway and chemosensitivity to ovarian carcinoma. METHODS: Tumor samples were obtained from 24 patients with epithelial ovarian carcinoma before and after chemotherapy with cisplatin, doxorubicin, and cyclophosphamide. Mutations in the p53 gene were screened by polymerase chain reaction-single-strand conformation polymorphism analysis and determined by cycle sequencing. Expression of the p53, Bax, and bcl-2 proteins and proliferating cell nuclear antigen (PCNA) were determined by immunohistochemical staining. Apoptotic cells were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling method. RESULTS: Of the 24 patients, 12 responded to chemotherapy and 12 did not. p53 gene mutation was observed in ten nonresponders and two responders. The incidence of p53 protein expression in tumors with the gene mutation was 58% (7 of 12) and was 17% (2 of 12) in tumors without the gene mutation. A significant reverse correlation between apoptotic index (AI) and labeling index (LI), determined by the percentage of PCNA positive cells, was observed in tumors after chemotherapy. AI was found to increase significantly after chemotherapy in tumors with the wild-type p53 gene (3.84 +/- 1.64 vs. 7.13 +/- 5.23) but LI did not change in either tumor type. The expression of Bax protein was significantly greater in tumors with the wild-type p53 gene after chemotherapy. bcl-2 protein expression did not relate to p53 gene status before or after chemotherapy. CONCLUSIONS: The current study suggests that p53-dependent apoptosis in tumors is strongly related to the chemosensitivity in epithelial ovarian carcinoma.     

卵巢上皮性癌中p53和VEGF表达的相互关系及其临床意义

目的研究p53及血管内皮生长因子(VEGF)在卵巢上皮性癌组织中的表达,探讨其相关性以及它们对卵巢上皮性癌预后的影响.方法应用免疫组化法检测60例上皮性卵巢癌p53蛋白和VEGF表达.结果在卵巢上皮性癌中,p53蛋白表达率为53.3%(32/60),p53蛋白表达与肿瘤的临床病理特征及患者预后无显著相关性.26例(43.3%)患者VEGF表达阴性或低度表达,34例(56.7%)患者VEGF蛋白高度表达.VEGF蛋白高度表达与肿瘤的临床分期、细胞分化程度及患者结局有显著相关性.VEGF蛋白高度表达者生存率比VEGF无或低度表达者低.多变量回归模型分析表明,肿瘤FIGO分期及VEGF表达是影响上皮性卵巢癌患者术后存活时间的独立预后因素.Spearman相关分析显示,VEGF与p53在卵巢上皮癌中的表达呈正相关(r=0.396,P=0.002).结论 p 53蛋白与VEGF表达呈正相关,VEGF可作为判断卵巢上皮癌预后有价值的指标.     

Clinical significance of serum tenascin-c levels in epithelial ovarian cancer

Tenascin-C (TNC) is an extracellular matrix protein that is expressed at low levels in normal adult tissue but is highly expressed around many tumors including ovarian tumors. The objective of this study was to determine the clinical significance of the serum levels of TNC in epithelial ovarian cancer (EOC) patients. A total of 50 patients with a pathologically confirmed diagnosis of EOC were included in this study. Serum TNC levels were determined by the solid-phase sandwich enzyme-linked immunosorbent assay (ELISA) method. Age- and sex- matched 28 healthy controls were included in the analysis. Median age of the patients was 56.5 years old, range 22 to 83 years. Majority of the patients had advanced disease (FIGO stage III–IV) (90 %). The median serum TNC levels were found significantly higher in EOC patients (130.5 pg/mL) compared to healthy controls (90.1 pg/mL) (p?=?0.03). We found no correlation between serum TNC levels and any prognostic parameters analyzed, including age of the patients, histology, tumor grade, stage of the disease, and response to chemotherapy. Survival analysis did not show statistically significant effect of serum TNC concentration on progression-free and overall survival (p?=?0.36 and p?=?0.19, respectively). However, patients with high serum TNC levels tend to have poor overall survival. In conclusion, although serum TNC levels are elevated, it has no predictive or prognostic roles on survival in EOC patients.     

Clinical significance of serum p53 antibodies in oral cancer

AIM AND BACKGROUND: The incidence and mortality due to oral cancer have increased worldwide. In India, the use of tobacco has been found to be the major etiological factor for the development of oral cancers. Various studies on serum p53 antibodies have suggested their clinical importance as prognostic markers in cancer. However, there is a dearth of data on serum p53 antibodies in oral cancer patients in India. The present study was carried to evaluate the clinical significance of serum p53 antibodies in oral cancer. MATERIALS AND METHODS: The serum p53 antibody status was analyzed by means of ELISA in 55 healthy individuals, 60 patients with oral precancerous conditions, 75 untreated oral cancer patients, and 86 follow-up blood samples of the oral cancer patients. RESULTS: We found serum p53 antibodies in 23% of cancer patients.The frequency of p53 antibody positivity was higher in patients with lymph node metastasis, advanced disease and well-differentiated tumors. Furthermore, p53 antibody positivity strongly correlated with poor treatment outcome in cancer patients. Kaplan-Meier survival analysis showed significantly poorer disease-free survival in patients with serum p53 antibodies. CONCLUSION: The results of this study suggest the usefulness of serum p53 antibodies in the prognostication of oral cancer patients.     

Clinical significance in molecular detection of p53 mutation in serum of patients with colorectal carcinoma

Circulating DNA can be isolated from serum of patients with various carcinomas and p53 mutation can be observed in colorectal carcinoma. The aim of this study was to investigate the correlation between p53 mutation in DNA extracted from colorectal carcinoma and that in DNA extracted from serum of patients with colorectal carcinoma. The clinical significance in molecular detection of p53 mutation in serum of patients with colorectal carcinomas was also investigated. DNA was extracted from tumors and non-tumorous colorectal tissues of 46 patients with single sporadic colorectal carcinomas of stage I (n=6), stage II (n=18), stage III (n=15), and stage IV (n=7) according to the TNM classification. Circulating DNA was also extracted from the serum of the 46 patients with colorectal carcinoma and from 7 healthy volunteers for normal control. Mutations of the p53 gene were analyzed using a fluorescence-based polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) method. DNA sequences were determined in DNA fragments with shifted peaks by SSCP methods. Mutations in tumors were found in 22 (48%) of 46 patients, and mutations in serum were found in 3 (14%) of these 22 patients. Of 4 patients with stage IV disease, 3 (75%) had serum p53 mutation and the mutation pattern of these 3 patients was the same in both tumor and serum. No correlation was seen between p53 mutation in serum and the level of serum DNA. There was no significant difference between the presence of p53 mutation in serum and tumor size, depth of invasion, vascular invasion, or lymph node metastasis. However, liver metastasis showed significant difference (p=0.0026). The presence of p53 mutation in serum was associated with a clinically advanced stage accompanied by liver metastasis.     

卵巢上皮性肿瘤患者血清层粘连蛋白检测的临床意义

目的:探讨卵巢上皮性肿瘤患者血清层粘连蛋白含量及临床意义.方法:应用放射免疫技术测定48例卵巢恶性上皮性肿瘤患者术前血清层粘连蛋白(LN)含量,并测定了其中43例患者术后血清LN含量.结果:卵巢恶性上皮性肿瘤组术前血清LN含量显著高于对照组及良性肿瘤组(P＜0.01),术后明显下降,手术前后血清LN含量差异有显著性意义(P＜0.05);卵巢恶性上皮性肿瘤患者低度分化组血清LN含量显著高于中度及高度分化组(P＜0.05),腹水阳性组LN含量显著高于腹水阴性组(P＜0.05),晚期患者血清LN含量明显高于早期患者(P＜0.05).结论:卵巢恶性上皮性肿瘤患者血清LN含量与肿瘤的浸润及转移过程密切相关;观察血清LN含量及其变化,对卵巢恶性上皮性肿瘤患者的病情及预后判断有重要的参考价值.     

p53与c-myc和cyclin B1在卵巢上皮性癌组织中的表达及意义

目的：研究 p53、c-myc和cyclin B1在卵巢良性肿瘤及上皮性卵巢癌组织中表达的相关性及临床意义.探讨p53、c-myc和cyclin B1在上皮性卵巢癌组织发生、发展中的作用.方法：应用免疫组化SP法检测61例上皮性卵巢癌、29例卵巢良性上皮性肿瘤和12例正常卵巢组织的p53、 c-myc和cyclin B1基因蛋白表达情况,并分析它们之间的关系.结果：上皮性卵巢癌中p53、c-myc和cyclin B1表达率分别为50.82%（31/61）、60.66%（37/61）和49.18%（30/61）; 在良性卵巢上皮性肿瘤中p53、c-myc和cyclin B1的蛋白表达率分别为10.34%（3/29）、17.24%（5/29）和13.79%（4/29）.p53、c-myc和cyclin B1在Ⅰ、Ⅱ期与Ⅲ、Ⅳ期上皮性卵巢癌组织中的阳性表达,差异均有统计学意义,P=0.032 81.p53、c-myc和cyclin B1在上皮性卵巢癌G1与G2、G3的阳性表达,差异有统计学意义,P=0.041 08.在正常卵巢组织中均未见p53、c-myc和cyclin B1蛋白的表达.结论：p53、c-myc和cyclin B1作为细胞周期调节因子参与上皮性卵巢癌的发生、发展,其协同作用促进上皮性卵巢癌的发生、发展并可能与预后有关.     

MMP-2在上皮性卵巢癌中的表达及临床意义

目的:探讨MMP-2在上皮性卵巢癌中的表达及临床意义.方法:15例正常卵巢组织、15例良性上皮性卵巢肿瘤组织, 89例上皮性卵巢癌组织标本,用免疫组化法检测MMP-2蛋白表达.结果:正常卵巢组织及良性卵巢肿瘤组织中,MMP-2蛋白不表达或低表达.上皮性卵巢癌中,MMP-2表达水平明显升高,高表达率为50.6%.MMP-2高表达与肿瘤晚期、瘤细胞的低分化、肿瘤转移有显著的相关性(P<0.05).结论:上皮性卵巢癌组织中,MMP-2蛋白表达上调.MMP-2蛋白在上皮性卵巢癌的生长和转移过程中发挥重要作用,有可能作为判断卵巢癌预后的指标.     

p53 and related proteins in epithelial ovarian cancer

We conducted a retrospective immunohistochemical evaluation of the prognostic significance of the expression of p53 and the related proteins Bax, Bcl-2, growth arrest and DNA damage (Gadd45), murine double minute 2 (Mdm2) and p21^WAF1/CIP1 in chemonaïve tumours taken from 66 patients with ovarian cancer. Ki-67 expression (a marker of cell proliferation) was also evaluated immunohistochemically, while apoptosis within malignant cells was determined with the terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling (TUNEL) assay. The expression of each of the following proteins was significantly associated in the tumours (P<0.05 unless otherwise stated): Bax with Bcl-2 (P<0.01); Bax with Mdm2; p21^WAF1/CIP1 with Gadd45 (P<0.01); p21^WAF1/CIP1 with p53; p53 with Mdm2. Univariate analysis showed that expression of p53, Bax, bulk residual disease and International Federation of Gynecology and Obstetricians (FIGO) stage were all strongly correlated with response to chemotherapy (P<0.01). Similarly, the FIGO stage and Ki-67 expression (P<0.01), as well as pathological subtype and bulk residual disease (P<0.05), were prognostic factors for disease progression. The FIGO stage and Ki-67 expression were significant prognostic factors for overall survival (P<0.01), with Gadd45 expression and pathological subtype also significant (P<0.05) in a univariate analysis. Multivariate analysis for response to chemotherapy showed that expression of p53, Bax and FIGO stage were all independent prognostic factors (P<0.01). The FIGO stage was the most important independent prognostic factor for progression and survival on multivariate analysis (P<0.01). However, Ki-67 expression was also an independent prognostic factor for disease progression (P<0.05) and approached significance for survival (P=0.055). Taken together, these data suggest that determination of Ki-67 expression could supplement established prognostic factors.     

p53和p21WAF1/CIP1基因在上皮性卵巢癌中的表达及临床意义

目的探讨联合检测p53和p21蛋白表达与上皮性卵巢癌预后的关系.方法 108例上皮性卵巢癌标本用于研究,每个标本同时用免疫组化的方法检测p53和p21蛋白表达.结果 p53(－)和p53( )患者的5年生存率分别为60.47%和29.43%,差异有显著性(P=0.0228).p21(－)和p21( )患者的5年生存率分别为31.58%和47.14%,差异有显著性(P=0.0246).p53(－)而p21( )患者的预后明显优于其他患者(P=0.0013).多因素分析显示p53、p21蛋白联合表达状态是判断上皮性卵巢癌预后的独立因子. 53蛋白表达与p21蛋白表达呈负相关(P=0.0003).结论联合检测p53、p21蛋白表达在判断上皮性卵巢癌预后上的意义优于单纯检测p53或p21蛋白表达,对临床有指导意义.     

The prognostic significance of p53 tumor suppressor gene alterations in ovarian carcinoma

BACKGROUND: The prognostic significance and nature of p53 dysfunction in ovarian carcinoma is unclear. The relation between p53 overexpression, p53 mutations, and their effects on overall survival in primary ovarian carcinoma is explored. METHODS: Tumor specimens from 171 consecutive epithelial ovarian carcinomas were examined for overexpression of p53 protein with DO7 antibody. P53 mutations were determined by direct sequencing. The influences of conventional histopathologic prognostic factors and various p53 molecular alterations on overall survival were assessed. RESULTS: Overall, 48.5% and 57.3% of the samples showed p53 overexpression and p53 mutation, respectively. Although neither p53 overexpression nor the mere presence of a p53 mutation impacted overall survival, the combination did prognosticate survival both in univariate and multivariate models. The authors' results suggest 4 mechanisms that may affect p53 dysfunction in nearly 100% of advanced stage ovarian carcinomas. These include null mutation, nonresponsive p53 (wild-type [wt] p53 sequence, DO7 negative), sequestration (wt p53 sequence, DO7 positive), and missense mutation. Median survival for these groups that constitute sequentially 21.3%, 20.5%, 12.3%, and 45.9% of the 122 Stage III or IV (International Federation of Gynecology and Obstetrics) cancers was 1.49, 1.31, 3.09, and 3.6 years, respectively. The nonresponsive p53 and null sequence tumors grouped together as functionally null convey the worst prognosis relative to missense mutations in a univariate model (P = 0.006). Functionally null p53 (P = 0.002), stage (P = 0.008), and optimal cytoreduction (P = 0.008) were independent prognostic factors by multivariate analysis. CONCLUSIONS: Sequestration of wt p53 is unique to advanced stage ovarian carcinoma. Functionally null p53 represents an independent molecular predictor of compromised survival.     

大肠癌组织中p53蛋白和增殖细胞核抗原表达的临床意义

目的探讨增殖细胞核抗原(PCNA)和p53蛋白在大肠癌中的表达及临床意义.方法应用免疫组化S-P方法检测60例大肠腺癌中的PCNA及p53蛋白的表达.结果大肠癌中p53蛋白阳性表达率为63.3%,PCNA增殖指数为(78.2±24.5)%,p53蛋白表达阳性者其细胞增殖活性为(83.1±18.6)%,明显高于p53蛋白阴性组(61.2±11.3)%(P＜0.01).p53蛋白阳性表达率与PCNA增殖指数随着大肠癌病理分级的上升而增加,且与预后呈负相关.结论同时检测p53蛋白、PCNA对大肠癌的诊断、病理分级及预后的评估有重要的指导意义.     

Overexpression and mutation of p53 in epithelial ovarian cancer

We examined p53 expression in 107 epithelial ovarian cancers with immunohistochemical techniques using monoclonal antibody PAb1801. High level expression of nuclear p53 protein was detected in the malignant epithelium in 54 (50%) of these cancers. Expression of p53 protein was undetectable in 13 benign gynecological tissues. p53 mRNA from three cancers that overexpressed the protein were sequenced and point mutations which altered the coding sequence of the highly conserved region of the gene were found in each case. Three cancers with undetectable protein levels also were sequenced and were found to be wild-type through the same region of the gene. As in other cancers, overexpression of the p53 protein in ovarian cancer appears to correlate closely with the presence of mutation in the p53 gene. p53 overexpression did not correlate with stage, histological grade, or the ability to perform optimal cytoreductive surgery. A significant correlation (P = 0.04) was observed between p53 overexpression and aneuploidy in advanced stage (III/IV) disease. There was no significant relationship between overall survival and p53 expression. Since mutation and overexpression of p53 are common in epithelial ovarian cancers, further studies are warranted to clarify the role of p53 in ovarian tumorigenesis.     

Prognostic significance of p53 mutation and p53 overexpression in advanced epithelial ovarian cancer: a Gynecologic Oncology Group Study.

PURPOSE: The prognostic significance of p53 mutations and overexpression in advanced epithelial ovarian cancers was examined in primary tumors from 125 patients participating in a Gynecologic Oncology Group randomized phase III treatment protocol. PATIENTS AND METHODS: Mutational analysis of p53 was performed in RNA or genomic DNA extracted from frozen tumor. An immunohistochemistry assay was used to detect p53 overexpression in fixed tumor. RESULTS: There were 81 patients (74%) with a single mutation, three patients (3%) with two mutations, and 25 patients (23%) lacking a mutation in exons 2 to 11 of p53. Although most mutations occurred within exons 5 to 8, mutations outside this region were observed in 11% of patients. A mutation in exons 2 to 11 of p53 was associated with a short-term improvement in overall survival and progression-free survival. Adjusted Cox modeling demonstrated a 70% reduction in risk of death (P =.014) and a 60% reduction in risk of disease progression (P =.014) for women with such mutations. However, these striking risk reductions increased over time (P <.02) and eventually disappeared with longer follow-up. Overexpression of p53 was observed in 55 patients (100%) with only missense mutation(s), seven patients (32%) with truncation mutations, and eight patients (40%) lacking a mutation in exons 2 to 11. Overexpression of p53 was associated with tumor grade but not with patient outcome. CONCLUSION: Alterations in p53 are a common event in advanced epithelial ovarian cancer. A mutation in p53, but not overexpression of p53, is associated with a short-term survival benefit. Additional studies are required to define the roles that p53 plays in regulating therapeutic responsiveness and patient outcome.     

Prognostic importance of DNA ploidy and p53 in early stages of epithelial ovarian carcinoma.

Patients with early stages (FIGO stages IA-IIC) of ovarian cancer continue to experience tumor relapses and they succumb due to their disease after seemingly adequate adjuvant therapy. In a series of 113 patients treated with adjuvant radiotherapy 4-6 weeks after primary surgery, the DNA content and p53 status of the tumors were studied and related to other known prognostic factors (age, FIGO stage, histopathologic type, and tumor grade). The DNA analyses were done by flow cytometry and p53 expression was studied by immunohistochemistry on formalin-fixed and paraffin-embedded tissue. DNA analyses of 103 tumors could be made and the p53 status was determined in 106 cases. Univariate analyses showed that both p53-positivity and aneuploidy of the ovarian tumors were strongly associated with tumor grade. There was also a strong association between p53 expression of the tumors and DNA aneuploidy (DNA index >1.10 and S-phase fraction >11.5%). P53-positivity and tumor grade were the only significant factors for the risk of tumor recurrence. DNA and p53 status alone were not adequate predictive factors to identify clinically relevant subgroups of patients who would benefit from adjuvant postoperative therapy. Tumor grade remains the most important prognostic factor with regard to the risk of tumor recurrence and the cancer-specific survival rate in early stage ovarian carcinoma. Overexpression of p53 also increases the risk of tumor recurrence.     

Alteration of p53 gene in ovarian carcinoma: clinicopathological correlation and prognostic significance.

Inactivation of the tumour-suppressor gene p53 has been demonstrated in a variety of human tumours. We extracted DNA from paraffin-embedded tissues of 67 ovarian carcinoma samples (54 primary tumours, seven metastases and six tumours obtained after chemotherapy), and analysed allelic losses and mutations of the p53 gene using single-strand conformation polymorphism (SSCP) analysis of DNA fragments amplified by a polymerase chain reaction (PCR). Allelic loss was observed in 24 of 32 informative cases. The mutation was detected in 14 of 54 primary ovarian carcinomas: eight serous cystadenocarcinomas (SCA), 42%), five endometrioid adenocarcinomas (EA, 42%) and one mucinous cystadenocarcinoma (14%). The incidence of the alteration was higher in SCA and EA than in other histological types, but the difference was not statistically significant. The incidence of p53 gene abnormalities in ovarian carcinomas tended to be increased in patients with disease advanced (over FIGO stage II). Mutations were found in exons 5 and 7 only and consisted mainly of single nucleotide substitutions [9 or 14 (64%) in exon 7; 4 of 14 (29%) in exon 5]. In 13 of 14 cases, p53 gene mutations occurred concomitantly with losses of the normal allele. The status of the p53 gene in metastases and the tumours obtained after chemotherapy was identical to that in the primary tumours. The presence of p53 gene mutation did not correlate with histological grade, response to primary therapy and survival. These findings suggest that mutational alterations of the p53 gene are involved in the development of a significant proportion of some ovarian carcinomas (SCAs or EAs), especially in advanced stages. However, they may not be a marker predicting the biological behaviour or the outcome of the disease.     

卵巢上皮性癌患者血清无细胞DNA的检测及临床意义

目的：检测循环无细胞DNA中的肿瘤相关cfDNA（ALU247／ALU115）及CA-125基因片段（CA125-cfDNA）在卵巢上皮性癌患者血清中的表达，探讨其是否可作为卵巢上皮性癌早期诊断及病情监测的指标。方法：采用半定量RT-PCR方法检测48例卵巢上皮性癌、16例良性卵巢上皮性肿瘤和12例正常健康对照血清中游离的ALU247、ALU115、CA125、β-actin DNA片段的表达。结果：卵巢上皮性癌患者血清中的肿瘤相关cfDNA（ALU247／ALU115）和CA125-cfDNA的相对水平（CA125-cfDNA／β-actin）明显高于卵巢良性肿瘤患者、正常对照及术后化疗二疗程者的值，晚期患者（Ⅲ-Ⅳ期）血清中的表达明显高于早期患者（Ⅰ-Ⅱ期），早期患者的表达明显高于正常对照组（P〈0．05），该两项指标与病理学类型及病理分级无关。CA125-cfDNA的相对水平与血清CA125的值存在相关性，在晚期卵巢上皮性癌未化疗患者腹水中的值显著高于血清中的值（P〈0．05）。结论：检测血清中ALU247／ALU115及CA125-cfDNA基因片段的水平可作为血清CA125的有效补充指标，用于卵巢上皮性肿瘤良恶性鉴别诊断、早期诊断和病情监测。     

卵巢浆液性肿瘤组织CIP2A和p53表达临床意义探讨

目的探讨CIP2A和p53在卵巢浆液性腺癌（ovarian serous adenocarcinoma,OSA）和卵巢交界性浆液性肿瘤（ovarian borderline serous tumor,OBST）中表达及其与临床病理参数和预后相关性。方法选取南京军区南京总医院1998-04-29-2010-10-02原发性OSA手术切除标本95例;另外选取南京军区南京总医院2007-06-25-2010-11-09原发性OBST 11例和南京市妇幼保健院2005-08-17-2012-04-10原发性OBST 27例,总计38例OBST作为对照。应用免疫组织化学方法测定95例原发性OSA和38例OBST中CIP2A及p53的表达,运用χ2检验分析CIP2A和p53表达与临床病理参数关系,运用非参数Spearman相关系数检验两者之间的相关性,并对随访结果进行生存分析。结果 95例OSA中CIP2A和p53高表达率分别为76.8%和68.4%,38例OBST中CIP2A和p53的高表达率分别为13.2%和44.7%,CIP2A和p53在OSA中的表达均明显高于OBST,差异有统计学意义,P〈0.05。CIP2A的表达水平与区域淋巴结转移、临床分期、病理分级和复发有关,P〈0.05;p53的表达水平与患者年龄、区域淋巴结转移、病理分级和复发密切相关,P〈0.05。Spearman相关系数检验结果显示,CIP2A和p53在OSA中的表达呈正相关,r=0.271,P=0.008,两者协同表达。Kaplan-Meier和Cox回归多因素分析显示,OSA患者预后与CIP2A和p53的表达有关,CIP2A和p53高表达的患者预后差,P〈0.05,但两者均不是影响OSA预后的独立因素。结论 CIP2A和p53高表达提示OSA恶性程度高。联合应用CIP2A和p53免疫组化标志可作为临床评估OSA患者预后的生物学指标。