Cyclin D1 overexpression and p53 mutation status in epithelial ovarian cancer

OBJECTIVE: To examine the cyclin D1 mRNA expression level in ovarian tumor samples as compared with normal ovaries and to determine the relationship between cyclin D1 overexpression and p53 mutation status in ovarian tumors. METHODS: mRNA was isolated and cDNA was prepared from 27 epithelial ovarian tumors (3 tumors of low malignant potential (LMP) and 24 cancers) and 6 normal ovaries. The cyclin D1 sequences were amplified by using a thermal cycler in parallel with the beta-tubulin gene as an internal control. The cyclin D1 mRNA expression level relative to beta-tubulin was determined by 32P phosphoimager analysis. To confirm the overexpression of the cyclin D1 protein in ovarian tumor cells, immunostaining was performed. The p53 gene mutation status was examined by direct cDNA sequencing. RESULTS: mRNA levels of cyclin D1 were significantly higher in 21 (78%) of the 27 ovarian tumors than in normal ovaries. Cyclin D1 overexpression was detected in ovarian LMP tumors as well as in ovarian cancer cases. Positive immunostaining of cyclin D1 protein was observed in 10 of 18 (56%) ovarian tumors examined. p53 mutations were found in 11 (61%) of 18 ovarian tumors. Of 11 ovarian tumor cases with p53 mutations, 5 showed overexpression of cyclin D1. All 7 ovarian tumor cases without p53 mutations showed significant cyclin D1 mRNA overexpression. CONCLUSION: Cyclin D1 overexpression seems to be an early genetic event in ovarian tumor development. Although p53 may be one of the proteins whose function regulates the expression of G1 cyclins, ovarian tumors with no p53 mutation consistently showed cyclin D1 overexpression. Cyclin D1 overexpression may play an important role in the tumorigenesis of epithelial ovarian tumors.     

Prognostic Significance of p53 Expression in Ovarian Granulosa Cell Tumors

Objective.The purpose of the study was to investigate the significance of p53 expression for the prognosis in patients with ovarian granulosa cell tumors (GCT).Methods.The records of 30 patients operated on for GCT at Tampere University Hospital, Finland, were reviewed. The mean age at the time of the diagnosis was 55 years. Twenty-one of the tumors were of FIGO stage I, three were of stage II, three were of stage III, and three were of stage IV. Paraffin-embedded tumor specimens were analyzed by immunohistochemistry for expression of mutated p53 protein and by flow cytometry.Results.Eleven tumors were positive for p53 and 19 were negative. The median crude survival of p53-negative patients was 10 times that of p53-positive ones (210 months vs 21 months,P= 0.037, log-rank test). The association between p53 immunoreactivity and stage was statistically significant (P= 0.026 Pearson χ²test), while there was no association between p53 expression and DNA ploidy or S-phase fraction.Conclusion.Although the results should be considered as preliminary, expression of mutated p53 in ovarian granulosa cell tumors seems to be associated with unfavorable prognosis.     

膜联蛋白A8在卵巢上皮性浆液性肿瘤中的表达及临床意义

目的:检测膜联蛋白A8(Annexin A8,ANXA8)在卵巢组织中的表达,探讨其表达与卵巢上皮性浆液性恶性肿瘤患者临床病理参数及预后的相关性。方法:采用免疫组织化学法检测75例卵巢组织(正常卵巢组织组11例、卵巢浆液性良性肿瘤组13例、卵巢浆液性交界性肿瘤组17例、卵巢浆液性恶性肿瘤组34例)中ANXA8的表达,分析其与卵巢癌患者临床病理参数及疾病预后的关系。结果:ANXA8主要定位于细胞膜及细胞质,ANXA8在卵巢浆液性恶性肿瘤组中的高表达率(23/34,67.65%)明显高于正常卵巢组织组(1/11,9.09%)、卵巢浆液性良性肿瘤组(3/13,23.08%)及卵巢浆液性交界性肿瘤组(5/17,29.41%),差异有统计学意义(P分别为0.001、0.006、0.010)。在34例卵巢浆液性恶性肿瘤患者中,FIGOⅢ~Ⅳ期患者的ANXA8的高表达率(21/24,87.5%)明显高于FIGOⅠ~Ⅱ期患者(2/10,20.0%),差异具有统计学意义(P<0.001);盆腹腔残余病灶直径>1 cm患者的ANXA8高表达率(15/17,88.2%)明显高于残余病灶≤1 cm患者(8/17,41.2%),差异有统计学意义(P=0.010)。Kaplan-Meier生存分析表明,FIGO分期、淋巴转移、残余病灶、ANXA8的表达都是影响总生存期(OS)的重要因素(均P<0.05)。Cox多元回归分析表明ANXA8的高表达是影响卵巢浆液性恶性肿瘤患者预后的独立危险因素(P=0.019,HR=11.465,95%CI:1.498~87.757)。结论:ANXA8在卵巢上皮性浆液性恶性肿瘤组织中表达升高,且与卵巢癌不良预后有关,可用于临床监测卵巢上皮性浆液性恶性肿瘤患者病情变化。     

The significance of p53 mutation and over-expression in ovarian cancer prognosis

Mutation of the p53 tumor suppressor gene is the most commonly observed genetic abnormality in human tumors and associations between p53 aberration and patient survival have been shown for several tumor types. Previous studies have found that approximately 50% of epithelial ovarian carcinomas exhibit abnormalities in the p53 gene. The aim of this study, therefore, was to examine the potential prognostic significance of aberrant p53 in patients with primary epithelial ovarian carcinoma. Using immunohistochemistry (IHC) and the anti-p53 antibodies CM1, PAb240 and PAb1801, p53 over-expression was observed in 20/39 (51%) tumors. When these results were combined with previously reported IHC and sequencing analyses, 37/61 (61%) tumors exhibited a p53 aberration. Although there was no significant difference between sequencing and IHC results, several cases gave discordant results, indicating that a combination of both methods may be required to estimate accurately the proportion of tumors with p53 aberrations. Univariate statistical analysis showed that p53 aberrations were significantly associated with tumor grade 3/4, FIGO stage III/IV, serous tumors and the presence of bulk (>2 cm) residual disease following surgery. In univariate survival analysis, tumor grade and stage, ascites and post-surgical residual tumor> 2 cm were associated with both overall survival (OS) and disease-free survival (DFS). p53 status, however, was not a predictor of either OS or DFS. Using the Cox proportional hazards model, only FIGO stage and post-surgical residual disease> 2 cm had an independent effect on OS and only stage was found to be an independent predictor of DFS. In conclusion, p53 mutation and overexpression does not appear to be a significant indicator of patient survival in this series of ovarian carcinomas.     

p53 Protein Expression in a Population-Based Series of Primary Vulval Squamous Cell Carcinoma and Immediate Adjacent Field Change

Objectives.Our aim was to study correlations between survival, disease recurrence, and p53 protein expression in a well defined population-based series of vulval squamous cell carcinoma and immediate adjacent epithelial skin changes.Methods.One hundred fifteen vulval squamous cell carcinoma were studied. Epithelial skin changes immediately adjacent to tumor were classified into nonneoplastic epithelial disorders (NNED) or vulval intraepithelial neoplasia (VIN). Archival specimens containing primary tumor and immediate adjacent skin were immunostained with a mouse monoclonal antibody to p53 protein.Results.p53 overexpression, defined as greater than 10% nuclear epithelial staining, was observed in 68% of tumors. Tumor immunostaining did not correlate with actuarial survival or disease-free interval. p53 overexpression was associated with a nonsignificant trend toward shorter disease-free interval in those tumors with nodal metastatic disease at diagnosis (P= 0.07). The only clinicopathological variable found to correlate with p53 expression was tumor grade (P= 0.002). Immediate adjacent abnormal skin changes were associated with p53 overexpression in 32% of cases. Adjacent normal skin did not immunostain for p53. p53 overexpression was most likely to occur in adjacent epithelial changes incorporating both NNED and high grade VIN (P= 0.005). Patterns of epithelial p53 overexpression in adjacent abnormal skin were either basal or full thickness. Full thickness epithelial p53 overexpression was most likely to occur in those disorders containing VIN (P< 0.0001). Positive immunostaining of adjacent skin abnormalities did not predict local tumor recurrence.Conclusions.This study demonstrates that although vulval squamous tumor p53 expression is not of prognostic significance, distinct immunostaining patterns can be observed in immediate adjacent skin. Vulval epithelial skin disorders displaying histological features of both NNED and VIN III may contain a profile of underlying molecular change which is of significance in subsequent tumor development.     

ras oncogene product p21 expression and prognosis of human ovarian tumors.

Monoclonal antibody rp-28 directed against the ras gene product p21 has been studied to evaluate ras p21 expression in malignant and benign ovarian tissues. Some ovarian carcinomas of serous and mucinous cystadenocarcinomas, undifferentiated adenocarcinomas, and clear cell carcinomas demonstrated intense staining of ras p21. The frequency and intensity of ras p21 staining were observed to increase with the degree of malignancy. There was no significant difference in ras p21 expression between early and late stages in ovarian tumors arising from the coelomic epithelium. With respect to prognosis, no differences between the ras p21-positive and -negative cases in ovarian tumors arising from the coelomic epithelium were observed. It is, therefore, possible to say that ras p21 expression was not related to clinical staging and prognosis. Expression of ras p21 in malignant lesions was higher than that in benign lesions of the ovary, and the expression is associated with the degree of malignancy in some types of ovarian tumors. Overexpression of ras p21 was observed in epithelial tumors; however, increased expression was not observed in germ cell and sex-cord stromal tumors. This differential expression of ras p21 is due to the different histogenesis of ovarian tumors. This fact may reflect a different carcinogenic mechanism for different types of malignancy.     

Abnormal Expression of the Retinoblastoma Gene in Ovarian Neoplasms and Correlation to P53 and K-ras Mutations

We analyzed the expression of the retinoblastoma (Rb) gene in a group of ovarian neoplasms previously characterized for mutations in the p53 suppressor gene and the Ki-ras oncogene. Using immunohistochemical techniques, a total of 59 ovarian neoplasms spanning the histiologic spectrum from benign to malignant were examined for the expression of the Rb protein. All benign cystic adenomas and low malignant potential tumors exhibited normal expression of the Rb protein. Abnormalities in Rb protein staining were noted in 3 of 22 (14%) ovarian carcinomas. The staining patterns included tumors that were totally or focally negative for Rb protein. One tumor focally expressed Rb. This tumor demonstrated a direct juxtaposition of sections of Rb expressing and nonexpressing malignant epithelial cells. Two of the three tumors with abnormal Rb expression also had p53 mutations and staining on serial sections demonstrated that selected ovarian cancer cells possessed mutations in both oncogenes. These data suggest that the loss of Rb gene expression may play a role in the pathogenesis of a small number of invasive ovarian malignancies, but not in noninvasive ovarian neoplasms.     

钙黏素6基因在卵巢肿瘤组织中的表达及突变的研究

目的　通过研究卵巢肿瘤组织中钙黏素 (cadherin) 6基因的表达、突变及其临床意义 ,以寻找与卵巢肿瘤发生相关的分子水平标志物。方法　应用RT PCR技术和PCR 单链构象多态性方法分别检测恶性卵巢肿瘤组织 (4 1份 )、良性卵巢肿瘤组织 (15份 )、正常卵巢组织 (17份 )中cadherin 6mRNA的表达及cadherin 6基因的突变情况 ,并分析其临床意义。结果　正常卵巢组织、良性卵巢肿瘤组织、恶性卵巢肿瘤组织中cadherin 6mRNA阳性率分别为 71%、5 3%、2 4 % ,前两者显著高于后者 (P<0 0 5 )。cadherin 6mRNA阳性率与恶性卵巢肿瘤手术病理分期有关 ,Ⅲ～Ⅳ期恶性卵巢肿瘤组织中 ,cadherin 6mRNA阳性率 (5 % )显著低于Ⅰ～Ⅱ期 (4 5 % ,P <0 0 1)。 4 1例恶性卵巢肿瘤患者中 ,2例出现cadherin 6基因突变 ,而在正常卵巢组织和良性卵巢肿瘤组织中无cadherin 6基因突变。结论　cadherin 6mRNA在晚期恶性卵巢肿瘤组织中表达缺失。提示cadherin 6mRNA表达可作为判断恶性卵巢肿瘤预后的一个指标     

Cyclin E mRNA overexpression in epithelial ovarian cancers: inverse correlation with p53 protein accumulation

OBJECTIVE:We investigated the relationship between cyclin E mRNA overexpression and p53 protein accumulation in epithelial ovarian cancers. METHODS: mRNA was isolated and cDNA was prepared from 36 epithelial ovarian tumors (three adenomas, three low malignant potential tumors, and 30 carcinomas), and six normal ovaries. The cyclin E mRNA expression levels relative to an internal control, beta-tubulin, were determined by semiquantitative polymerase chain reaction (PCR). Cyclin E and p53 protein expression in ovarian cancer tissues were examined by immunohistochemistry using the same series of samples. Fisher exact test of significance and an unpaired t test were used for statistical analysis. RESULTS: Considerable levels of cyclin E mRNA were detected in all normal ovaries and ovarian tumor samples examined by semiquantitative PCR amplification. mRNA levels of cyclin E were significantly higher in nine of 30 (30%) ovarian cancers compared with those in normal ovaries. The immunohistochemical expression of cyclin E protein was confirmed in the nuclei of tumor cells in 13 of 30 (43%) ovarian cancers. p53 protein accumulation was detected in 12 of 30 (40%) ovarian cancers examined. There was a significant inverse correlation between cyclin E mRNA overexpression and p53 protein accumulation (P <.01, Fisher exact test). CONCLUSIONS: Cyclin E mRNA overexpression frequently occurs in ovarian cancers without p53 protein accumulation. Cyclin E might have an important effect on the development of a limited number of ovarian cancers.     

Quantification of p53 in Epithelial Ovarian Cancer

Objective.The perceived function of wild-type p53 is suppression of cell proliferation. An alteration in the p53 tumor suppressor gene is a common defect in human malignancies. The purpose of this study was to prospectively determine whether p53 expression, as quantified by image analysis, was related to traditional prognostic indicators as well as survival in patients epithelial ovarian cancer.Methods.Eighty-three consecutive patients with epithelial ovarian cancer had their p53 expression studied by immunohistochemical staining and quantified by image analysis. Unless otherwise noted, p53 expression was reported as the percentage positive nuclear area staining.Results.The mean follow-up was 37 months (median, 30 months; range 24–55 months). In patients with serous carcinomas of the ovary, the mean p53 expression was 29.4%, whereas in patients with other histologies, the mean was 10.5% (P< 0.001). The tumors of patients with stage III or IV tumors stained significantly higher (mean 28.7%) than the tumors of patients with stage I or II disease (mean 8.36%) (P< 0.001). The tumors of patients with disease which could be optimally cytoreduced stained significantly lower (mean 23.0%) than the tumors of patients whose disease was unable to be optimally cytoreduced (mean 28.6%) (P= 0.041). Utilizing survival as the endpoint for multivariate analysis, FIGO stage (P= 0.006), p53 expression (P= 0.046), and the level of cytoreduction (P< 0.001) were independent prognostic indicators.Conclusion.Image analysis allows quantitative measurements of p53 staining. p53 staining is significantly higher in advanced-stage, high-grade tumors which are unable to be cytoreduced than in early-stage, low-grade tumors which can be optimally cytoreduced. p53 expression is an independent prognostic indicator of survival in patients with epithelial ovarian carcinomas.     

Chemotherapy induces death receptor 5 in epithelial ovarian carcinoma

OBJECTIVES: Defects in the apoptotic pathway are a general cause for drug resistance. Chemotherapy in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has proven to be an effective strategy to induce apoptosis in vitro in ovarian tumor cells. Systemic TRAIL administration might be a therapeutic option, since no toxicity was observed in nonhuman primates. In the present study, expression of TRAIL and its apoptosis-inducing death receptors (DR4 and DR5) and inhibitory decoy receptor (DcR1) was studied in normal ovaries and in malignant ovarian tumors before and after chemotherapy to investigate the therapeutic potential of TRAIL. METHODS: DR4, DR5, DcR1, and TRAIL were studied immunohistochemically in 5 normal ovaries, 15 stages I/II, and 26 stages III/IV primary ovarian cancers, including 19 paired tumor samples (pre- and post-chemotherapy). RESULTS: Surface epithelium of normal ovaries expressed TRAIL and its receptors; ovarian stromal cells expressed only DcR1. Of the ovarian cancers, 73% expressed DR4, 51% DR5, 46% DcR1, and 34% TRAIL. Most primary ovarian cancers (88%) expressed at least one death receptor. TRAIL expression was lower in stage III/IV than in stage I/II tumors (P<0.05). In paired samples, DR5 immunostaining was more frequently (P=0.05) and stronger (P<0.01) expressed in residual tumors. CONCLUSION: Early stage tumors expressed TRAIL more frequently than advanced stage tumors. Most primary and residual ovarian tumors expressed at least one TRAIL death receptor, while in residual tumors following chemotherapy, DR5 was more frequently expressed. Therefore, human recombinant TRAIL administration might be an interesting treatment option.     

Aurora-Ipl1激酶1 mRNA在卵巢恶性肿瘤组织中的表达及其意义

目的 :研究卵巢恶性肿瘤组织中Aurora Ipl1激酶 1(AIK1)mRNA的表达 ,探讨AIK1基因与卵巢肿瘤发生的关系。方法 :采用半定量逆转录聚合酶链反应 (RT PCR)检测 2 7例卵巢恶性肿瘤、15例卵巢良性肿瘤或瘤样病变、12例正常卵巢组织中AIK1mR NA。结果 :AIK1mRNA在卵巢恶性肿瘤组织中的表达显著高于卵巢良性病变 (P <0 .0 5 )及正常组织 (P <0 .0 5 )。AIK1mRNA的表达与年龄、组织学类型、分期、腹水等无关 (P >0 .0 5 )。结论 :卵巢恶性肿瘤中AIK1mRNA表达上调 ,提示AIK1基因与卵巢癌发生有关     

卵巢肿瘤组织中p53和P－糖蛋白的表达及其临床意义

目的：评价卵巢肿瘤组织中突变型ｐ５３基因和Ｐ－糖蛋白（Ｐ－ｇｐ）表达的临床病理意义及其相互关系。方法：采用免疫组织化学法测定卵巢恶性肿瘤５３例，卵巢良性肿瘤２０例和正常卵巢组织１７例的ｐ５３和Ｐ－ｇｐ的表达，并与临床病理因素进行相关分析。结果：１．卵巢恶性肿瘤组织中ｐ５３和Ｐ－ｇｐ阳性表达率分别为４６．７％和３５．８％，卵巢良性肿瘤和正常卵巢组织中则无一例ｐ５３和Ｐ－ｇｐ表达。２．Ⅲ～Ⅳ期患者和低分化卵巢恶性瘤组织中ｐ５３表达阳性率高于Ⅰ～Ⅱ期和高、中分化者，而Ｐ－ｇｐ表达与临床分期、组织学类型和分级无明显相关性。３．Ｐ－ｇｐ表达阳性和阴性的卵巢恶性肿瘤患者，对化疗的有效率分别为３１．６％和６４．７％，而ｐ５３阳性表达与化疗效果无明显相关性。结论：组织中的ｐ５３和Ｐ－ｇｐ表达测定对判断卵巢恶性肿瘤的预后和对化疗的敏感性有一定的价值。     

Estrogen and progesterone receptors in human ovarian tumors

Estrogen and progesterone receptors were measured in cystosols prepared from 32 normal ovaries and 25 benign and 49 malignant ovarian tumors. In normal ovarian tissue, estrogen and progesterone receptors were detected in 22 and 75% of specimens, respectively. Estrogen receptors were present in low concentrations ranging from 2 to 9 fmol/mg cytosol protein. The estrogen receptor content and distribution were similar in benign tumors (20%), but progesterone receptors were significantly decreased in 16% of specimens (P less than 0.001). In malignant ovarian tissues, estrogen receptors were present in 57% of specimens in concentration ranging from 1 to 132 fmol/mg cytosol protein. Of these, 72% of tissues had estrogen-receptor concentrations greater than 10 fmol/mg cytosol protein. The presence of estrogen receptors in ovarian cancer was significantly different from normal ovaries and benign tumor tissues (P less than 0.01). Progesterone receptors were detectable in 29% of ovarian cancer specimens. Estrogen and progesterone receptors were present alone or in combination, in 65% of ovarian cancers. The similarity in sex steroid content between ovarian and breast cancer warrants prospective studies of sex steroid receptor content in ovarian malignancies as a possible predictive index of survival and response to hormone therapy.     

p21: a monitor of p53 dysfunction in ovarian neoplasia

p53 is an important tumor suppressor gene which is activated in response to DNA damage. The induced expression of p53 causes either cell cycle G1 arrest or apoptosis. The recently cloned p21 gene (WAF1/CIP1/SDI1) is known to be directly activated by wild-type but not mutant p53 and can suppress the growth of human cells in G1 by inhibiting the activity of cyclin-dependent kinases (CDKs). As p21 is activated by p53 and is a negative regulator of the cell cycle, it is possible that p21 could be a sensitive marker to monitor p53 function. To investigate the mRNA expression level and mutation status of p53 and p21 genes, quantitative polymerase chain reaction (PCR) and direct cDNA sequence analysis were performed. mRNA expression levels of p53 and p21 genes relative to the β-tubulin gene were examined in 32 ovarian tumors (24 carcinomas, six low malignant potentials (LMPs), two benigns) and six normal ovaries. Of 13 ovarian tumors with p21 underexpression, nine p53 mutated cases (69%) and one polymorphism case were found. Among nine p53 mutated cases, three cases showed p53 overexpression, another three cases showed p53 underexpression and a further three cases showed normal expression of p53. These findings suggest that mRNA underexpression of p21 may be a more useful indicator of p53 dysfunction than mRNA expression of p53.     

Apoptotic Index in Ovarian Carcinoma: Correlation with Clinicopathologic Factors and Prognosis

The apoptotic index (apoptotic cells/1000 tumor cells, AI) was evaluated in 71 ovarian carcinomas, all surgically resected. Apoptosis was examined by modified terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate–biotin nick end-labeling (TUNEL) method in histologic sections. High AI (≥2.8) significantly correlated with high mitotic index (P= 0.05), high histologic grade of the tumor (P= 0.018), and short overall survival (P= 0.017). An inverse relationship between AI and bcl-2 protein expression was also observed (P= 0.007). In addition, AI was assessed in 5 ovarian epithelial tumors of borderline malignancy, and all were categorized as low AI (<2.8). No significant correlation was found between AI and other clinicopathologic factors, such as age, clinical stage, lymph node metastasis, tumor size, histology of the tumor, and expression of p53 protein. Multivariate survival analysis showed that only clinical stage (P= 0.0395) and mitotic index (P= 0.0387) had independent prognostic value, whereas AI did not. Our results suggest that counting apoptosis can be useful for predicting the patient survival in ovarian carcinoma, although AI is not an independent prognostic factor. It is also suggested that bcl-2 protein is an important regulator of apoptosis in ovarian carcinoma.     

Expression of epidermal growth factor receptor in normal ovary and in ovarian tumors.

Increased expression of epidermal growth factor (EGF) receptor has been recorded in many types of human tumors and has been associated with reduced survival in ovarian carcinoma. The purpose of this study was to examine the immunocytochemical distribution of the EGF receptor in normal ovaries (n = 30) and in ovarian tumors (n = 126). Staining was observed in two normal ovaries, in the granulosa cells of a developing follicle, and in surface epithelium. Forty-seven of 103 malignant common epithelial tumors were immunopositive. Staining was usually focal, always confined to the neoplastic epithelium, and showed a cytoplasmic distribution. There was a slight trend for increased EGF receptor expression in more advanced common epithelial malignancies, but this was not statistically significant. No correlation between immunoreactivity and histological subtype or grade of tumor was seen. A few other tumors were also examined: one each of Brenner tumor, mature teratoma, mature teratoma with squamous carcinoma, borderline serous tumor and fibroma; all were immunopositive.     

免疫球蛋白IgG在卵巢上皮性癌中的表达

目的探讨正常卵巢、卵巢良性肿瘤、卵巢上皮性癌中免疫球蛋白IgG的表达。方法采用免疫组化染色，应用兔抗人IgG多克隆抗体对42例卵巢上皮性癌、10例卵巢良性肿瘤、10例正常卵巢进行检测，并用计算机图像分析系统检测IgG的表达情况。结果上述三类组织中均存在不同程度的IgG表达，阳性表达基本定位于细胞浆。卵巢上皮性癌组织中IgG阳性表达的相对面积和平均光密度均显著高于正常卵巢（P〈0．01），正常卵巢与卵巢良性肿瘤之间在阳性表达相对面积上有明显差异，在平均光密度比较中没有明显差异。结论卵巢上皮性癌中存在免疫球蛋白IgG的高表达。     

Expression of cyclooxygenase-2 in association with clinicopathological prognostic factors and molecular markers in epithelial ovarian cancer

OBJECTIVES: This study examines whether expression of COX-2 is associated with clinicopathological features and other molecular markers of ovarian cancer. METHODS: Sixty-four paraffin-embedded tissue specimens were obtained from patients with ovarian cancer who received cytoreductive surgery and combination chemotherapy. Tissue specimens were subjected to immunohistochemical analysis using antibodies to COX-2, p53, and VEGF. RESULTS: Increased COX-2 expression significantly correlated with histologic type (mucinous 5.6% vs. non-mucinous 65.2%, P<0.001). COX-2 expression was also significantly associated with stage, tumor grade, residual disease status, and presence of ascites. COX-2 expression correlated positively with expression of p53 (P=0.006) and VEGF (P=0.025). Although survival was lower in patients with high COX-2 expression than in those without high COX-2 expression (P<0.001), only tumor grade and stage were independent prognostic indicators. In patients with non-mucinous cancer, COX-2 expression correlated with stage (P<0.001) and presence of ascites (P=0.033). CONCLUSIONS: Our results suggest that expression of COX-2 in ovarian cancers is specific to histologic type of tumor and is associated with poor clinicopathologic prognostic factors. Expression of COX-2 also correlates well with expression of p53 and VEGF.     

Is it possible to diagnose malignancy from fluid in cystic ovarian tumors?

Objective

p53 gene mutations are frequently identified in ovarian cancer tissue. The aim of this study was to investigate whether wild type or mutated genomic DNA can be identified in ovarian cystic fluid specimens.

Study design

Forty-eight Japanese patients with cystic ovarian tumors (30 benign cysts, 8 borderline malignant tumors, and 10 cancers) were investigated. Cystic fluid and tumor tissue were obtained during surgery. After DNA extraction from the cystic fluid, polymerase chain reaction (PCR) and sequence analysis for exons 4–9 of the p53 gene was performed. In two cases of mucinous cystic tumor of borderline malignancy and endometrioid adenocarcinoma, the p53 gene sequences were determined. Immunohistochemical staining for abnormal p53 gene product was also performed.

Results

DNA was successfully extracted from all cystic fluid specimens. Furthermore, exons 4–9 of the p53 gene could be identified by electrophoresis from all samples. In a mucinous cystic tumor of borderline malignancy, one point mutation was identified at codon 223 in exon 6 (CCT→CTT) of the p53 gene. Aberrant p53 gene product was also observed in the tumor cells by immunohistochemical staining. Moreover, in another case of endometrial adenocarcinoma, a point mutation at codon 245 in exon 7 (GGC→AGC) was detected by the direct sequencing of the amplified Exon. Notably, the mutation was not present in the peripheral blood (PB) sample and tissue specimens from the patient.

Conclusion

In cystic ovarian tumors, cystic fluid may provide informative material for molecular studies since it reflects the p53 status of tumor tissue in the cyst wall. This system might help to identify ovarian malignancy without resection of the tumor tissues.