VEGF、MMP2、MVD与卵巢癌临床病理关系的研究

目的 :研究卵巢癌中VEGF、MMP2的表达和MVD与临床病理参数和预后的关系并探讨其临床价值。方法 :采用免疫组化技术检测 5 3例卵巢癌和 10例卵巢交界性肿瘤中VEGF、MMP2的表达水平 ,用CD34标记新生血管内皮细胞 ,在显微镜下观察血管密度。结果 :卵巢癌中MVD与年龄呈正相关 (P =0 .0 16 ) ,粘液性囊腺癌中MVD高于其它组织学类型 (P <0 .0 1)。卵巢癌中VEGF的表达与FIGO手术分期呈正相关 (P =0 .0 0 1) ,VEGF表达还与腹水量呈正相关 (P =0 .0 0 2 )。MVD与VEGF、MMP2表达呈正相关 (P值分别为 0 .0 2 1和 0 .0 31) ,VEGF表达与MMP2表达呈正相关 (P =0 .0 0 2 )。VEGF、MMP2强阳性表达和MVD较高 (≥ 10 /HP)的患者预后差 (P值分别为 0 .0 2 6 ,0 .0 36和 0 .0 38)。结论 :VEGF是重要的血管生成因子 ,MMP2不仅在肿瘤的浸润和转移中意义重大 ,而且在肿瘤的血管生成中发挥作用。卵巢癌的FIGO手术分期、MVD及VEGF、MMP2表达与预后相关 ,特别是MMP2在肿瘤的浸润、转移和血管生成中有双重作用 ,既有助于判断患者对传统治疗的敏感性 ,而且对开发针对肿瘤的生物特异性治疗具有启发作用。     

Foxp3在卵巢上皮性癌组织中的表达及其与预后相关性的研究

目的:探讨Foxp3在卵巢上皮性癌组织中的表达及其与预后的相关性。方法:选取2003年1月至2007年12月在上海交通大学医学院附属仁济医院诊治的卵巢上皮性癌患者的组织标本,用免疫组化法测定Foxp3在卵巢良性上皮性肿瘤、交界性上皮性肿瘤和恶性上皮性肿瘤组织中的表达,并比较卵巢上皮性癌相关的临床指标及病理学因素。结果:Foxp3在卵巢上皮性癌中阳性表达率为56.7%(17/30),显著高于卵巢良性上皮性肿瘤(0%,0/10)和交界性卵巢肿瘤(20%,2/10)(P=0.001,P<0.05)。Foxp3的表达与组织学分级显著相关(P=0.004)。Foxp3(+)与Foxp3(-)患者的生存曲线差异接近统计学差异水平(P=0.057)。结论:Foxp3表达升高与卵巢癌的预后不良存在相关趋势。     

细胞周期p16-cyclin D1-pRb调节通路与人卵巢浆液性囊腺癌的相关性研究

目的 :探讨细胞周期 p16 - p Rb- cyclin D1调节通路及各因子在浆液性卵巢肿瘤发生和发展中的作用。方法 :应用免疫组化 L s AB法检测一组浆液性卵巢肿瘤中 p16、p Rb和 cyclin D1蛋白表达情况。结果 :卵巢浆液性囊腺癌原发灶和淋巴结转移灶中 p16表达阳性率明显低于正常卵巢、良性肿瘤和交界性肿瘤 ;p16 - p Rb- cyclin D1调节通路异常率却呈相反趋势变化 ,且通路异常与浆液性囊腺癌 FIGO分期、组织学分级及预后无明显相关性。 p16表达阳性患者术后生存率高于阴性患者 (P=0 .0 0 0 6 )。p Rb和 cyclin D1表达情况与卵巢浆液性囊腺癌组织学分级、FIGO分期无明显关系。卵巢浆液性肿瘤组织中 p16和 p Rb蛋白表达呈负相关。结论 :p16蛋白在卵巢浆液性肿瘤的发生、发展中可能起着较为重要的作用。 p16 - p Rb- cyclin D1调节通路异常在浆液性卵巢肿瘤虽很常见 ,但其具体作用尚不清楚     

MMP-9及TIMP-1在卵巢上皮性肿瘤中的表达

目的 :探讨MMP 9和TIMP 1在卵巢上皮性肿瘤中的表达。方法 :采用免疫组化方法检测 12 5例卵巢上皮性肿瘤及 7例正常卵巢组织中MMP 9和TIMP 1的表达。结果 :MMP 9在交界性 (5 .4 0± 2 .2 8)和恶性卵巢上皮性肿瘤 (6.88± 2 .0 9)中的表达显著高于良性卵巢上皮性肿瘤 (3.80± 1.5 6)和正常卵巢组织 (2 .69± 1.19) (P <0 .0 1) ;TIMP 1在正常卵巢组织、良性、交界性和恶性卵巢上皮性肿瘤中的表达分别为 1.86± 1.10、3.89± 1.11、3.97± 0 .98和 4 .99± 1.70 ,差异有显著性 (P <0 .0 1)。结论 :MMP 9可能参与卵巢上皮性肿瘤的发生和侵袭 ,TIMP 1在卵巢肿瘤的演化过程中除可抑制肿瘤的侵袭和转移外 ,可能还有非MMP 9抑制活性的作用     

Galectin-3、CAⅨ在卵巢上皮性肿瘤的表达及意义

目的探讨半乳糖凝集素-3(Galectin-3)、碳酸酐酶Ⅸ(CAⅨ)在卵巢上皮性肿瘤的表达情况,探讨二者在恶性卵巢上皮性肿瘤发生、发展中的作用及相关性。方法采用免疫组化SP法检测45例良性卵巢上皮性肿瘤,50例交界性卵巢上皮性肿瘤及61例恶性卵巢上皮性肿瘤中Galectin-3、CAⅨ的表达情况。结果 1 Galectin-3、CAⅨ在恶性卵巢上皮性肿瘤中的阳性表达率分别为67.2%和59.0%,明显高于良性及交界性组,差异有统计学意义(P0.01,P0.05)。Galectin-3及CAⅨ在恶性卵巢上皮性肿瘤中的表达与肿瘤分化程度、浸润、转移密切相关(P0.05)。而与肿瘤的组织学类型及患病年龄状况无关(P0.05);2恶性卵巢上皮性肿瘤组织中Galectin-3与CAⅨ的表达呈正相关(r=0.672,P0.01)。结论 Galectin-3、CAⅨ在恶性卵巢上皮性肿瘤的发生过程中发挥重要作用,参与肿瘤浸润、转移,可能成为指导肿瘤预后的参考指标。     

血清基质金属蛋白酶-9测定在诊断卵巢肿瘤和评估预后中的价值

目的 :探讨测定血清基质金属蛋白酶 - 9(MMP - 9)的含量对诊断卵巢上皮癌的价值及它与患者预后的关系。方法 :将卵巢上皮癌 (OEC) 43例 ,卵巢交界性肿瘤(BOT) 12例及卵巢良性肿瘤 (OBT) 2 4例分为 3个研究组 ,2 0例正常妇女为对照组 ,用ELISA法测定各组术前血清中的MMP - 9含量。结果 :(1)OEC、OBT、BOT及对照组血清MMP - 9的中位数分别为 534.6 0、2 79.19、2 0 0 .54、55.56ng L ,上述各组的范围分别为 111.18～ 176 6 .12ng L、16 .38～ 874 .34ng L、2 5.10～ 4 2 3.2 9ng L、11.0 1～ 2 0 1.6 3ng L。OEC组血清MMP - 9水平高于OBT、BOT及对照组 ,差异有显著性 (P <0 .0 5) ;(2 )OEC患者按临床分期、病理分级、组织学类型、淋巴或大网膜转移等影响患者预后的因素分组 ,各组间血清MMP - 9水平无显著性差异。结论 :患者血清MMP - 9水平与卵巢肿瘤的恶性行为有关 ,对诊断有一定的价值 ,但用于判断患者预后的价值有限     

卵巢上皮性肿瘤cyclinE表达的临床意义

目的 :检测卵巢上皮性肿瘤中cyclinE的表达 ,分析其临床意义。方法 :应用免疫组化S -P法检测cyclinE在 2 0例良性、10例交界性、55例恶性卵巢上皮性肿瘤中的表达情况 ,并分析它们与临床病理指标的关系。结果 :cyclinE在良性、交界性、恶性卵巢上皮性肿瘤中表达总阳性率分别为 30 %、50 %、78.18% ,强阳性率分别为 10 %、2 0 %、4 3.6 % ,差异均有显著性。在恶性卵巢上皮性肿瘤中cyclinE阳性表达与低组织分化 ,淋巴结转移及腹水显著有关 (P <0 .0 5) ,cyclinE阳性的肿瘤细胞多发生转移 ,预后差。结论 :cyclinE在卵巢上皮性肿瘤中的表达 ,可作为估计卵巢肿瘤恶性程度和预后的重要指标之一     

cyclin D1蛋白表达与卵巢浆液性肿瘤预后的关系

目的 :探讨cyclinD1蛋白表达与卵巢浆液性肿瘤患者预后的关系。方法 :采用免疫组化SP法检测 91例卵巢浆液性肿瘤和 2 4例有癌转移的淋巴结中cyclinD1蛋白表达 ,并以 10例正常卵巢组织作对照。结果 :正常卵巢组织、良性浆液性卵巢肿瘤、交界性瘤、浆液性卵巢腺癌和转移性卵巢腺癌癌细胞的cyclinD1蛋白表达阳性率分别为 0、10 .0 %、53.3 %、83.9%和 83.3%。交界性瘤、浆液性卵巢腺癌和有癌转移的淋巴结组织中cyclinD1蛋白表达阳性率显著高于正常卵巢组织和良性浆液性卵巢肿瘤。cyclinD1蛋白表达阳性的浆液性卵巢腺癌患者预后较好 ,但并非卵巢浆液性囊腺癌患者独立的预后因素。结论 :cyclinD1癌基因在卵巢浆液性恶性肿瘤的发生过程中起重要作用。cyclinD1蛋白过表达可能是浆液性卵巢癌患者预后良好的指标 ,但并非影响预后的独立因素     

卵巢浆液性和粘液性肿瘤共享结肠癌抗原决定簇

以抗结肠癌单克隆抗体ＳＣ１３Ａ为探针，应用免疫组织化学染色法，分别对６７例卵巢浆液性和４４例卵巢粘液性肿瘤组织，以及２０例正常卵巢组织中相应的抗原表达进行检测。结果：在浆液性囊腺瘤、交界性囊腺瘤和乳头状囊腺癌中ＳＣ１３Ａ抗原的表达率分别为８．０％，７１．４％和９０．０％；在粘液性囊腺瘤、交界性囊腺瘤和乳头状囊腺癌中ＳＣ１３Ａ抗原的表达率分别为２５．８％、８０．０％和８７．５％；正常卵巢组织中无３Ｃ１３Ａ抗原表达。浆液性、粘液性的交界性囊腺瘤和乳头状囊腺癌的抗原表达率，均显著高于浆液性、粘液性囊腺瘤及正常卵巢组织（Ｐ＜０．００５）。提示：浆液性和粘液性肿瘤抗原之间有内在的联系，这两类肿瘤的抗原中均共同享有与结肠癌抗原相同的抗原决定簇，这种抗原位点在恶性肿瘤中的表达明显高于良性肿瘤。     

eIF4A在卵巢上皮性癌中表达及其与预后的关系

目的:检测真核细胞起始因子4A(e IF4A)在不同卵巢组织中的表达,探讨其临床意义及其与预后的关系。方法:利用荧光实时定量PCR及Western blot法检测42例卵巢上皮性癌(EOC)组织、15例卵巢交界性上皮性肿瘤组织、15例卵巢良性上皮性肿瘤组织和20例正常卵巢组织中e IF4A mRNA及蛋白的表达情况,同时采用免疫组化SP法检测123例EOC石蜡切片中e IF4A蛋白表达情况,并评估影响患者总生存率的高危因素。结果:EOC中e IF4AmRNA及蛋白表达显著高于交界性、良性及正常卵巢上皮组织(P0.05);交界性上皮肿瘤组织明显高于良性及正常卵巢上皮组织(均P0.05);卵巢良性上皮性组织略高于正常卵巢组织,但差异无统计学意义(P0.05)。EOC中e IF4A表达与FIGO手术病理分期、组织学分级、淋巴结转移及腹水情况有关(P均0.05),而与年龄及组织学类型无关(P0.05)。Kaplan-Meier生存曲线显示,e IF4A蛋白高表达者的总生存率明显低于低表达者(Log-Rank检验,P0.05)。COX比例风险模型分析发现,临床病理分期、组织学分级及术后有无残余瘤灶是EOC患者的独立预后因素(P0.05)。结论:e IF4A在EOC的发生进展中可能起重要作用,有可能成为判断预后的指标之一。     

卵巢囊腺肿瘤中增生细胞核抗原及p53蛋白表达的意义

用免疫组化ＡＢＣ方法检测了６０例卵巢囊腺肿瘤组织中增生细胞核抗原（ＰＣＮＡ）和ｐ５３蛋白的表达。结果表明：ＰＣＮＡ和ｐ５３蛋白在良性囊腺瘤、交界性囊腺瘤和囊腺癌三类不同性质的病变中表达存在显著的差别（Ｐ〈０．００１，Ｐ〈０．０５）。ｐ５３蛋白与ＰＣＮＡ表达关系密切，高增生指数（ＰＣＮＡ＋＋＋）肿瘤ｐ５３蛋白阳性率高，低增生指数肿瘤（ＰＣＮＡ＋，－）ｐ５３表达率低。认为在卵巢囊腺肿瘤中检测ＰＣＮＡ和     

卵巢上皮性肿瘤组织中KiSS-1、基质金属蛋白酶9和核因子κBp65蛋白的表达及其相关性

目的 探讨KiSS-1、基质金属蛋白酶9（MMP-9）、核因子κB（NF-κB）p65蛋白3者在卵巢上皮性肿瘤组织中的表达及其相关性。方法 采用免疫组化方法检测50份卵巢上皮性癌（卵巢癌）、20份卵巢交界性肿瘤、20份卵巢良性肿瘤和10份正常卵巢组织中KiSS-1、MMP-9、NF-κBp65蛋白的表达,并分析其临床意义及3者间的相关性。结果 KiSS-1蛋白在卵巢癌组织中的阳性表达率（80％）明显高于良性肿瘤组织及正常卵巢组织（分别为35％、10％;P〈0．05）;在卵巢交界性肿瘤组织中阳性表达率（65％）明显高于正常卵巢组织（P〈0．05）。在卵巢癌组织中,KiSS-1蛋白阳性表达率与淋巴结转移有关（P〈0．05）,与手术病理分期、病理类型及病理分级均无关（P〉0．05）;MMP-9蛋白阳性表达率与手术病理分期及淋巴结转移有关（P〈0．05）,而与病理类型及病理分级均无关（P〉0．05）;NF-KBp65蛋白阳性表达率与手术病理分期、病理分级及淋巴结转移有关（P〈0．05）,而与病理类型无关（P〉0．05）。在卵巢癌组织中,KiSS-1与MMP-9、NF．KBp65蛋白表达呈显著负相关关系（rs=-0．547,P〈0．05;rs=-0．414,P〈0．05）;MMP-9与NF-κBp65蛋白表达呈显著正相关关系（rs=0．695,P〈0．05）。结论 KiSS-1基因可能对卵巢癌的转移起一定的抑制作用;KiSS-1基因可能通过抑制MMP-9、NF-κB基因,从而发挥抑制卵巢癌转移的作用。     

Differential expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 protein and mRNA in epithelial ovarian tumors

OBJECTIVE: Matrix metalloproteinase-9 (MMP-9) can degrade gelatin and type IV collagen and is known to play an important role in tumor cell invasion across the basement membrane. The tissue inhibitor of metalloproteinase-1 (TIMP-1) is able to prevent activation of pro-MMP-9 and forms a 1:1 complex with the active form of MMP-9. The aim of the present study was to investigate the expression of MMP-9 and TIMP-1 in benign, borderline, and invasive epithelial ovarian tumors. MATERIALS AND METHODS: A total of 90 patients with epithelial ovarian tumor were treated at the Brigham and Women's Hospital and were used as the study population. Immunohistochemistry and in situ hybridization were performed to detect protein and mRNA expression of MMP-9 and TIMP-1. RESULTS: In the 90 epithelial ovarian tumors tested, MMP-9 expression in tumor cells was found to be significantly enhanced in serous and mucinous ovarian carcinomas compared with benign and borderline tumors. We also observed the immunostaining of MMP-9 in stromal cells of benign, borderline, and invasive epithelial ovarian tumors. Moreover, the expression levels of TIMP-1 in tumor cells were significantly higher in borderline and invasive ovarian tumors than in benign tumors. CONCLUSION: Using an in situ hybridization technique, we disclosed a direct correlation between the presence of mRNA and protein expression for both MMP-9 and TIMP-1. The present data suggest that high levels of MMP-9 protein in invasive epithelial ovarian carcinoma are strongly associated with tumor cell invasion. Enhanced expression of TIMP-1 protein in borderline and invasive tumors indicates that endogenous TIMP-1 protein may play a paradoxical role in ovarian tumor progression.     

Expression of matrix metalloproteinases and related tissue inhibitors in the cyst fluids of ovarian mucinous neoplasms

OBJECTIVES AND METHODS: The growth of an ovarian cystic neoplasm often involves its invasion into and destruction of the extracellular matrix. We examined neoplastic cysts of ovarian mucinous tumors for the presence of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) using zymography (in situ zymography, gelatin zymography, and casein zymography) and enzyme-linked immunosorbent assay. RESULTS: Matriolytic activity was detected within the cystic contents and cytoplasm of the lining epithelial cells of the cyst by in situ zymography. This intracystic matriolytic activity was thought to originate mainly in the epithelial cells. The activated form of MMP-9 was seen in all carcinoma and borderline fluids and in 7 of 15 adenomas. The concentration of MMP-9 was higher in carcinoma fluids than in borderline and adenoma fluids (P < 0.05). TIMP-1, which specifically binds to MMP-9, was also higher in carcinoma and borderline fluids than in adenoma fluids (P < 0.05). MMP-2 activity was nearly ubiquitously present in all cyst fluids, irrespective of the fluid's histologic category. The amount of MMP-2 was highest in the carcinoma category, although not to a statistically significant degree. TIMP-2, a specific inhibitor for MMP-2, was significantly lower in the borderline category than in the adenoma category. The molar ratios of TIMP-1/MMP-9 (not significant) and TIMP-2/MMP-2 (P < 0.05) were higher in the adenoma category. Expressions of trypsin, MMP-7, and MMP-9 were generally higher in carcinoma and borderline fluids than in adenoma fluids. CONCLUSIONS: These observations indicate the importance of ovarian cystic fluids for analyzing tumor-associated matriolytic activities. The findings suggest that these matriolytic enzymes, together with the presence of their inhibitors, play an important role in the growth of ovarian mucinous tumors.     

Prognostic value of matrix metalloproteinase-9 (gelatinase-B) expression in epithelial ovarian tumors

PURPOSE OF INVESTIGATION: To determine the expression of matrix metalloproteinase-9 (MMP-9) expression in malignant and borderline ovarian tumors and its correlation to prognosis. METHODS: Forty-five patients with primary epithelial ovarian tumors were enrolled in this retrospective study from 1988 to 2002. Only malignant (n = 30) and borderline (n = 15) ovarian tumors constituted the study group. All cases were surgically staged according to FIGO criteria. Patient characteristics and clinico-pathological findings were obtained from hospital records. Paraffin-embedded tissue blocks were treated with MMP-9 immunohistochemical stain. The percentage of the total number of tumors staining positively was categorised and awarded a score of 0 to 4: < 5% as 0, < or = 6-25% as 1, 26-50% as 2, 51-75% as 3 and 76-100% as 4. The intensity of immunostaining was scored on a 3-point scale: 1, weak; 2, moderate and 3, intense. A weighed score for each tumor specimen was produced by multiplying the percentage score with the intensity score and was defined as the 'epithelial MMP-9 score'. Stromal staining was also assessed as weak, moderate and intense. Cases with final epithelial MMP-9 scores < or = 6 and > 6 were then recategorised into two groups, accordingly. Based on degree of stromal staining, cases were recategorised into two final groups as mildly stained and intense or moderately stained. Tumor stages were regrouped as early (Stage I-II) and late (Stage III-IV), respectively. RESULTS: Mean ages of cases with malignant and borderline ovarian tumors were 57.2 +/- 3.1 and 49.7 +/- 2.1 years, respectively. Epithelial MMP-9 scores were higher in malignant tumors compared to borderline tumors (p = 0.014). However, with regard to stromal MMP-9 staining, no significant difference was observed among malignant and borderline tumors (p = 0.113). Among malignant ovarian tumors, epithelial MMP-9 scores did not differ between early versus late-staged and well versus poorly differentiated tumors. Median survival time of cases with epithelial MMP-9 scores < or = 6 and > 6 were 24 months and 32 months, respectively (log-rank: 0.93, p = 0.335). Cases with weak stromal MMP-9 staining had a longer median survival (48 months) compared to cases with moderate or intense stromal MMP-9 staining (24 months, log-rank: 4.46, p = 0.03). CONCLUSION: Epithelial MMP-9 expression generally appears in the malignant form of ovarian tumors compared to borderline tumors. MMP-9 expression in the stroma but not in the epithelium contributes to poor survival in ovarian cancers.     

Computed Tomography and Clinical Analysis of Ovarian Mucinous Tumors in Adolescent Patients

Study ObjectiveTo investigate the clinical and computed tomography features of ovarian mucinous tumors in children and adolescents.Design, Setting, and ParticipantsA retrospective analysis of clinical and preoperative computed tomography (CT) data was performed in 59 patients who were 20 years or younger with ovarian mucinous tumors confirmed by histopathology. Patients’ age, medical history, symptoms, tumor marker levels, and CT imaging findings were recorded.InterventionsNone.Main Outcome MeasuresIdentification of the clinical and CT features of ovarian mucinous tumors in pediatric and adolescent patients.ResultsThere were 41 mucinous cystadenomas in 39 cases, 12 borderline mucinous cystadenomas in 11 cases, and 9 mucinous cystadenocarcinomas in 9 patients. A total of 55 tumors were multilocular (55/62, 88.7%), including fewer than 10 loculations in 23 tumors, 10–20 loculations in 17 tumors, and over 20 loculations in 15 tumors. Eleven borderline mucinous cystadenomas were multilocular (11/12, 91.7%), with over 10 loculations in 7 tumors (7/12, 58.3%). Twelve tumors appeared as multilocular cystic-solid (12/62, 19.4%), and a case of mucinous cystadenocarcinoma was predominantly solid (1/62, 1.6%). Seventeen tumors showed honeycomb sign and stained glass appearance. Six mural nodules, with sizes ranging from 1.1 to 3.5 cm (average: 2.8 cm), were found in borderline mucinous cystadenoma and mucinous cystadenocarcinoma.ConclusionsThe CT findings of ovarian mucinous tumors in children are characteristic. The preoperative CT is helpful in making differential diagnoses.     

Clinical characteristics and prognosis of mucinous tumors of the ovary

OBJECTIVE: Ovarian mucinous tumors consist of benign, borderline, and carcinomatous tumor, but the clinical characteristics of these 3 types have not been investigated in detail. In this study, we compared the clinical characteristics and prognosis among these 3 types of mucinous tumors. METHODS: One hundred sixty-one patients with mucinous cystadenocarcinoma and 143 patients with mucinous borderline tumor were registered between 1986 and 2003. All patients were reviewed by two pathologists, then the mixed type and cases showing other organized malignant tumors were excluded from this study. Patients with mucinous carcinoma staged Ib or more were treated postoperatively with 6 cycles of platinum-based chemotherapy. Survival probability was analyzed by the Kaplan-Meier method and differences in survival rates were calculated using log-rank test. RESULTS: Mean patient ages were 43.9, 44.7, and 49.7 years in patients with benign, borderline, carcinomatous tumor, respectively. The ratio of early stage (I, II) to advanced stage (III, IV) was significantly lower in carcinoma than in borderline tumor. The levels of tumor markers tended to increase with the level of malignancy. CA72-4 is the most useful discriminating marker according to ROC analysis. In borderline tumor, 5 patients died of disease, and all of these patients had stage III disease with residual tumor after the initial surgery. Patients with borderline tumor showed significantly better prognosis than those with carcinoma; however, there were no significant differences in prognosis between borderline tumor and carcinoma in patients with stage III tumor or residual tumor. CONCLUSIONS: In mucinous tumors, measurement of CA72-4 is recommended to distinguish malignant from benign tumors. Even in borderline tumor, patients with residual tumor showed a poorer prognosis than carcinoma, suggesting that complete resection is necessary for a good prognosis.     

卵巢上皮性肿瘤的临床病理特征及其细胞周期素D1和p53蛋白表达的研究

目的研究卵巢上皮性癌（卵巢癌）和交界性上皮性肿瘤的临床病理特征及其细胞周期素D1（cyclin D1）和p53蛋白表达的情况,探讨卵巢癌和交界性上皮性肿瘤在发病机制上的联系。方法分析45例卵巢癌（卵巢癌组）和54例卵巢交界性上皮性肿瘤（交界性肿瘤组）的临床病理资料,采用免疫组化法检测两组组织中cyclin D1、p53蛋白的表达情况,并分析其与临床病理特征的相关性。结果（1）临床病理特征：①年龄：交界性肿瘤组平均年龄为42．5岁（14～82岁）,中位数年龄41岁;卵巢癌组平均年龄为53．5岁（26～80岁）,中位数年龄51岁。②分期：按国际妇产科联盟（FIGO）分期标准,交界性肿瘤组Ⅰ期48例、Ⅱ期3例、Ⅲ期3例;卵巢癌组Ⅰ期6例、Ⅱ期8例、Ⅲ期26例、Ⅳ期5例。③病理类型：交界性肿瘤组以黏液型为主[占56％（30／54）],其次为浆液型[其中普通型11例,微乳头型5例;占30％（16／54）];卵巢癌组以浆液型（其中低度恶性19例,高度恶性3例）为主[占49％（22／45）]。④病理分化程度：卵巢癌组高分化5例,中分化17例,低分化或未分化23例。⑤预后：交界性肿瘤组5年生存率为98％,卵巢癌组为51％,两组比较,差异有统计学意义（P=0．000）。（2）cyclin D1和p53蛋白的表达及其与卵巢癌和交界性肿瘤临床病理特征的相关性：卵巢癌组cyclin D1和p53蛋白的阳性表达率分别为31％（14／45）和56％（25／45）,p53蛋白表达强度与病理分化程度呈正相关（r=0．320,P=0．032）;交界性肿瘤组cyclin D1和p53蛋白的阳性表达率分别为69％（37／54）和6％（3／54）。其中,普通型浆液性交界性肿瘤与高度恶性浆液性癌比较（两者cyclin D1蛋白阳性表达率分别为91％和26％,p53蛋白分别为0和58％）,差异有统计学意义（P〈O．01）;而微乳头型浆液性交界性肿瘤与低度恶性浆液癌比较（两者cyclin D1蛋白阳性表达率分别为3／5和2／3,p53蛋白分别为1／5和1／3）,差异则无统计学意义（P〉0．05）。结论cyclin D1蛋白的过度表达常见于卵巢浆液性交界性肿瘤及低度恶性浆液性癌组织中,而p53蛋白的过度表达更多见于高度恶性浆液性癌组织中。卵巢浆液性交界性肿瘤与高度恶性浆液性癌具有不同的发病机制,而微乳头型浆液性交界性肿瘤与低度恶性浆液性癌的关系可能更为密切。     

Cell proliferation activity unrelated to COX-2 expression in ovarian tumors

The objective of this study was to assess the expression of Cyclooxygenase-2 (COX-2) and cell proliferation activity (Ki67 expression) in benign, borderline, and malignant serous and mucinous ovarian tumors. Expression of COX-2 and Ki67 proteins were evaluated by immunohistochemistry, in paraffin-embedded sections of ovarian epithelial tumors. The study included 113 serous (67 benign, 15 borderline, and 31 malignant) and 85 mucinous (48 benign, 28 borderline, and 9 malignant) tumors, removed from women who underwent laparotomy between January 1997 and December 2003. From benign to malignant tumors, there was a progressive positive trend in COX-2 expression in both serous and mucinous tumors, more evident in mucinous ones (P < 0.001). Comparing histologic types, COX-2 expression was more prominent in serous than in mucinous benign tumors (P < 0.01), but this difference was not significant in the borderline (P= 0.11) or malignant categories (P= 0.71). There was a progressive Ki67 positivity in line with the tumor histologic gradient for both serous (P < 0.01) and mucinous lesions (P < 0.01), but this increasing expression did not correlate with COX-2 expression in the present series (P= 0.78). There was a higher COX-2 expression in serous ovarian adenomas than in mucinous ones. COX-2 positivity increases in line with the morphologic gradient, from benign to malignant in both histologic types, but it was more prominent in mucinous lesions, pointing to different oncogenic pathways related to different histologic types. A correlation between the expression of COX-2 and Ki67 was not found, suggesting that COX-2 may be required for carcinogenesis, but this pathway is not responsible for cell proliferation in ovarian tumors.