卵巢浆液性肿瘤中WT-1异常活化对ki-67和P53蛋白表达的调控作用

目的探讨卵巢浆液性肿瘤WT-1异常活化情况,并分析对ki-67和P53蛋白表达的调控作用及临床意义。方法随机选取我院卵巢肿瘤患者100例,其中卵巢浆液性囊腺瘤26例、交界性浆液性肿瘤15例、卵巢浆液性癌34例和卵巢黏液性癌25例,采用免疫组化检测WT-1、ki-67、P53蛋白的表达,并分析其与关系。结果在卵巢浆液性癌中WT-1阳性率为32.35%,显著高于交界性浆液性肿瘤,其中高级别浆液性癌中的阳性率为36.84%,又明显高于低级别浆液性癌(26.87%),组间比较差异具有统计学意义(P0.05),而在卵巢浆液性囊腺瘤中未见WT-1蛋白异常表达。在卵巢浆液性癌和交界性浆液性肿瘤中ki-67、P53蛋白的表达明显高于浆液性囊腺瘤(P0.05),ki-67和P53在不同级别卵巢癌中亦存在差异性表达(P0.05);在卵巢黏液性癌和浆液性癌组织中WT-1和ki-67、P53蛋白差异均未见统计学意义(P0.05)。Spearman等级相关分析显示,WT-1蛋白与ki-67、P53蛋白的表达均呈正相关(r=0.998和0.745,P=0.001)。结论卵巢浆液性癌中存在WT-1异常活化,且主要发生于高级别浆液性癌中,其可能通过调控ki-67、P53蛋白的表达而发挥癌基因的作用,检测WT-1蛋白对判断肿瘤性质和级别具有重要的指导价值。     

p73基因在卵巢上皮性肿瘤中的表达及甲基化研究

目的 探讨卵巢上皮性肿瘤中p73蛋白的表达和基因启动子的甲基化情况,并观察其与临床病理学特征的关系.方法 制备包括68例卵巢癌、37例卵巢交界性肿瘤和21例卵巢良性肿瘤的组织芯片,用免疫组织化学EnVision法检测上述组织中p73蛋白表达情况,用亚硫酸氧盐修饰后测序法检测13例新鲜卵巢癌组织及5例新鲜卵巢交界性肿瘤组织的p73基因启动子甲基化情况.结果 92.6％ (63/68)的卵巢癌表达p73,p73蛋白总体表达率均值为32％(p73表达率指p73阳性细胞数所占的百分比),其中浆液性癌( 26/26)的表达率均值为40％,高于其他组织类型的癌(P=0.006).按照卵巢癌发病模式区分,Ⅱ型卵巢癌p73表达率均值(40％)高于Ⅰ型卵巢癌(24％),P=0.010.卵巢癌中p73的表达与临床分期及组织学分级无相关性(均P＞0.05).卵巢交界性肿瘤组(30/37)和良性肿瘤组(12/21)p73的总体表达率均值分别为16％和15％,该两组肿瘤中浆液性肿瘤表达率均值均高于黏液性肿瘤(P-0.003,P=0.026).卵巢癌组的p73阳性表达率均值明显高于交界性肿瘤组和良性肿瘤组(均P ＜0.05),交界性肿瘤组与良性肿瘤组比较差异无统计学意义(P＞0.05).浆液性肿瘤( 49/53)中,卵巢癌组(26/26) p73阳性表达率均值明显高于交界性肿瘤组(12/14)和良性肿瘤组(11/13;P =0.024和P=0.002),而卵巢交界性肿瘤组和良性肿瘤组比较差异无统计学意义(P=0.428).黏液性肿瘤(15/27)中,卵巢癌组(6/7)p73阳性表达率均值高于良性肿瘤组( 1/8;p=0.032),而卵巢癌组与卵巢交界性肿瘤组(8/12)、交界性肿瘤组与良性肿瘤组比较,差异均无统计学意义(P=0.234和P=0.201).p73启动子的甲基化结果显示,13例卵巢癌有8例发生甲基化,但每例样本甲基化频率有所不同,总体甲基化频率均值为8.0％.5例交界性肿瘤有2例发生甲基化,总体甲基化频率均值为9.0％,两组比较差异无统计学意义(P＞0.05).卵巢癌组p73甲基化额率与组织类型、发病模式、组织学分级及临床分期均无相关性(均P＞0.05).结论 卵巢上皮性肿瘤多数表达p73,卵巢癌p73的表达率均值明显高于交界性肿瘤和良性肿瘤,浆液性肿瘤高于其他组织类型;p73蛋白表达率与p73基因甲基化程度不存在简单线性相关关系.     

基质金属蛋白酶-7在卵巢浆液性肿瘤中的表达

目的：探讨MMP－7在卵巢浆液性肿瘤中的表达情况。方法：采用免疫组化SP法对6例正常卵巢、12例卵巢浆液性囊腺瘤、6例交界性囊腺瘤及22例卵巢浆液性囊腺癌MMP－7的表达进行了研究。结果：正常卵巢不表达MMP－7。大部分卵巢浆液性肿瘤的胞浆及间质中都有MMP－7的阳性表达。MMP－7的卵巢良性，恶性及交界性浆液性肿瘤胞浆中的表达无明显差异；而在肿瘤间质中，恶性及交界性卵巢浆液性肿瘤中的表达远高于良性肿瘤（P＜0．05）。在交界性及恶性浆液性卵巢肿瘤中，部分肿瘤细胞的细胞核中也有MMP－7的表达，为国内外首次报道。结论：MMP－7可能在卵巢浆液性肿瘤的进展中发挥重要作用。     

卵巢浆液性肿瘤中MCM4与Ki-67的表达及意义

目的 探讨微小染色体维持蛋白4(minichromosome maintenance proteins 4,MCM4)、Ki-67在卵巢浆液性肿瘤中的表达及意义.方法 采用免疫组化EliVision两步法检测MCM4、Ki-67蛋白在10例正常卵巢上皮组织(对照组)、19例卵巢良性浆液性嚢腺瘤、16例交界性浆液性肿瘤和43例浆液性腺癌中的表达.结果 MCM4在对照组、卵巢良性浆液性囊腺瘤、交界性浆液性肿瘤、浆液性腺癌的阳性表达率分别为10.00%、21.05%、43.75%、79.07%,Ki-67在对照组、卵巢浆液性乳头状腺瘤、交界性嚢腺瘤、浆液性腺癌的阳性表达率分别为10.00%、15.79%、25.00%、53.49%,其随着卵巢肿瘤病变的升级呈增高的趋势.MCM4在卵巢浆液性腺癌和交界性浆液性肿瘤中的表达与正常对照组相比差异具有统计学意义(P<0.05).Ki-67在卵巢浆液性癌和交界性浆液性肿瘤中的表达与正常对照组相比差异具有统计学意义(P<0.05).MCM4在卵巢浆液性癌中的表达与临床分期、病理分级及转移[淋巴结转移和(或)器官转移]有明显相关(P<0.05).Ki-67蛋白在卵巢浆液性癌中的表达与病理分级及淋巴结转移有明显相关(P<0.05),MCM4和Ki-67呈正相关.结论 MCM4、Ki-67为卵巢浆液性肿瘤的增殖指标,用于卵巢良、恶性肿瘤的鉴别和诊断,并可初步评估肿瘤预后,指导临床治疗.     

卵巢浆液性肿瘤中IQGAP1与E-cadherin表达的检测

目的探讨上皮性钙黏素(E-cadherin)与具有IQ结构域的人Ras GTP激活蛋白相关蛋白1(IQGAP1)在卵巢浆液性肿瘤中的表达及其临床意义。方法分别用免疫组织化学SP法和Western blot法检测20例卵巢浆液性囊腺癌、10例卵巢交界性浆液性囊腺瘤、10例卵巢浆液性囊腺瘤以及10例正常卵巢组织中E-cadherin和IQGAP1的蛋白表达。结果 E-cadherin蛋白在浆液性囊腺瘤中表达最高,明显高于正常卵巢组织和浆液性囊腺癌组织(P0.05),其均值高于交界性囊腺癌,无统计学意义。IQGAP1在卵巢浆液性囊腺癌中表达较正常卵巢组织、良性及交界性肿瘤组织均增高(P0.05);免疫组织化学染色证实IQGAP1在浆液性囊腺癌中以胞膜表达为主,而在良性肿瘤中以胞质表达为主。结论 E-cadherin和IQGAP1在卵巢浆液性瘤高表达,可联合用于卵巢浆液性肿瘤的免疫组化诊断。     

ataxin-3在卵巢浆液性肿瘤中的表达及其临床意义

目的检测ataxin-3在卵巢浆液性肿瘤中的表达及临床意义。方法采用免疫组化SP法检测ataxin-3在各组卵巢浆液性肿瘤中表达情况。结果ataxin-3在卵巢低级别浆液性囊腺癌中表达水平明显高于卵巢浆液性囊腺瘤、交界性浆液性囊腺瘤、高级别浆液性囊腺癌中的表达水平,但后三者之间无明显差异(P0.05),ataxin-3表达与卵巢浆液性囊腺癌的分化程度呈负相关,与其它临床病理因素均不存在相关性(P0.05)。结论ataxin-3可能参与卵巢低级别浆液性囊腺癌的发生机制,可能成为其早期诊断指标和治疗靶点。     

卵巢浆液性癌的研究进展

卵巢浆液性癌以前多认为是起源于卵巢表面上皮或上皮内陷形成的皮质包涵体。近年来,随着分子生物学与分子遗传学技术的不断发展,研究显示卵巢浆液性癌存在二元发病模式,分别为低级别与高级别浆液性癌。低级别癌由良性、交界性肿瘤发展而来,多伴有KRAS、BRAF或ERBB2突变;高级别卵巢癌大多来源于输卵管上皮,常伴有TP53突变。本文现从卵巢浆液性癌的组织学分级、免疫表型及组织起源方面作一综述。     

p16、p21在卵巢常见的上皮性肿瘤中的表达及鉴别诊断

目的探讨p16、p21在卵巢上皮性肿瘤中的表达及其鉴别诊断作用。方法采用免疫组化SP法检测314例卵巢上皮性肿瘤组织中p16、p21的表达。结果 (1)p16在卵巢浆液性腺癌、黏液性腺癌、内膜样腺癌中阳性细胞表达百分数以中位数(四分位间距)表示为80.00%(45.00%)、0.00(20.00%)、35.00%(48.75%),三者之间表达差异有统计学意义(P=0.00);p16在不同级别(良、交界性、恶性肿瘤)的卵巢浆液性肿瘤和子宫内膜样肿瘤中,随着肿瘤级别的升高,p16表达强度及阳性程度亦随之升高,差异具有统计学意义(P=0.001)。而在不同级别的卵巢黏液性肿瘤中p16的表达差异无统计学意义(P>0.05);(2)p21在不同类型卵巢上皮性肿瘤中的表达普遍较低,在卵巢浆液性腺癌、黏液性腺癌和子宫内膜样腺癌中表达阳性细胞百分数以中位数(四分位间距)表示分别为0.00(10.00%)、10.00%(15.00%)、0.00(7.50%),三者之间差异有统计学意义(P=0.000);p21在交界性肿瘤中的表达较在良性肿瘤与恶性肿瘤中的表达高,有统计学意义,卵巢恶性肿瘤与良性肿瘤之间表达差异无统计学意义。结论...     

三维超声及微血管密度在卵巢浆液性肿瘤病理性质中的研究

目的探讨良、恶性卵巢浆液性肿瘤三维超声形态特征及三维能量多普勒(3D-CPA)血流特点,并与病理微血管密度(MVD)进行相关性研究,为临床浆液性肿瘤的诊断提供依据。方法选择76例经手术切除的卵巢浆液性肿瘤患者,年龄26~71岁,平均年龄48.7岁。依据术后病理性质分为良性组(30例,病理结果为良性浆液性囊腺瘤,囊内可见分隔或乳头样实性组织,不包括单纯性浆液性囊腺瘤)、交界性组(24例,病理结果为交界性浆液性囊腺瘤)、Ⅰ期癌组(22例,病理结果为浆液性囊腺癌,国际妇产科联盟卵巢癌分期为Ⅰ期)。术前均经三维超声对肿瘤形态和血流进行观察,比较肿瘤直径、分隔数、分隔厚度、实性组织切面总面积、血流分级、血管指数(VI)。所选病例均进行免疫组织化学分析,计数MVD,研究超声测量结果与MVD的相关性。结果 3组之间分隔数、分隔厚度比较,良性组交界性组及Ⅰ期癌组(P0.05),交界性组与Ⅰ期癌组差异无统计学意义;3组肿瘤内实性组织切面总面积比较,良性组交界性组Ⅰ期癌组(P0.05),肿瘤直径差异无统计学意义(P0.05)。3D-CPA血管分级良性组以Ⅰ级血流多见,交界性组、Ⅰ期癌组以Ⅱ、Ⅲ级尤其以Ⅱ级多见;VI值比较,良性组交界性组Ⅰ期癌组(P0.05)。MVD 3组间存在差异,相关性分析显示,分隔数、分隔厚度、实性组织切面总面积与MVD呈正相关(r=0.247、0.469、0.717,P0.05),其中,分隔厚度、实性组织切面总面积相关性较好。MVD与肿瘤直径无显著相关性。交界性组、Ⅰ期癌组3D-CPA血管分级与MVD呈正相关(r=0.52、0.57,P0.05),VI与MVD亦呈正相关(r=0.49、0.58,P0.05)。结论三维超声观察卵巢肿瘤的形态及血流信号可提高对卵巢浆液性肿瘤良恶性的初步鉴别,为临床诊治提供依据。     

卵巢浆液性肿瘤中IGF-2R的表达及其意义

目的探讨胰岛素生长因子受体-2(insulin-like growth factor-2 receptor,IGF-2R)的表达及其与卵巢浆液性肿瘤临床病理特征的关系,分析IGF-2R表达对卵巢浆液性肿瘤的诊断及预后价值。方法收集10例正常卵巢上皮组织、15例良性浆液性卵巢肿瘤、15例交界性卵巢浆液性肿瘤及46例卵巢浆液性腺癌,采用免疫组化SP三步法检测IGF-2R的表达。结果 IGF-2R在100%(10/10)的正常卵巢上皮、93.3%(14/15)的良性浆液性卵巢肿瘤、86.7%(13/15)的交界性浆液性卵巢肿瘤和47.8%(22/46)的浆液性卵巢癌中呈阳性。IGF-2R在正常卵巢上皮组织与良性浆液性肿瘤组织中的表达差异无统计学意义(双侧P=0.405),IGF-2R在浆液性卵巢癌与交界性肿瘤、良性浆液性肿瘤、正常卵巢上皮组织中的表达差异有统计学意义(双侧P=0.008;P=0.002,P=0.003),IGF-2R表达与卵巢浆液癌临床分期、转移情况有关(P=0.003,P=0.032),与患者年龄、病理学分级、生存状态无关(P=0.181,P=0.180,P=0.118)。结论IGF-2R在卵巢表面上皮、良性浆液性肿瘤、交界性浆液性肿瘤和浆液性癌中表达呈逐步下调趋势。IGF-2R表达与卵巢浆液性腺癌的高临床分期、淋巴结转移呈负相关,可能成为卵巢浆液性肿瘤辅助诊断及临床预后的新指标。     

Incidence of P53 and K-ras alterations in ovarian mucinous and serous tumors

Clarification of the pathogenic relationships existing among ovarian cystadenomas, tumors of low malignant potential (LMP) and various adenocarcinoma types, a series of 29 mucinous and 19 serous ovarian tumors including adenomas, LMP tumors and adenocarcinomas were examined. P53 protein was detected by the streptavidin-biotin method and point mutation of K-ras codon 12 was detected by polymerase chain reaction-restriction fragment length polymorphism analysis. P53 overexpression was observed more frequently in serous adenocarcinomas (5/8, 63%) than in mucinous adenocarcinomas (2/9, 22%) and was correlated with the malignant potential of serous tumors. Furthermore, the proportion of P53-positive cells was significantly higher in serous adenocarcinomas than in mucinous adenocarcinomas. P53 overexpression may therefore be closely related to the early events of carcinogenesis in serous tumors. Although mutation of the K-ras oncogene appears to be an important event in the early tumorigenesis of mucinous tumors, mutation of the K-ras oncogene in serous tumors may be dependent on morphology. Different complex pathways of oncogene and/or tumor suppressor gene abnormalities may be involved in the development of mucinous and serous adenocarcinomas.     

Overexpression of p21WAF1/CIP1 and MDM2 characterizes serous borderline ovarian tumors

Ovarian epithelial tumors are classically divided into benign, malignant, and borderline or of low malignant potential. It is controversial whether this last group of tumors should be considered benign or malignant. Expression of cell cycle markers has recently been linked to tumor behavior and response to treatment. It has been shown that one of the pathways through which the p53 gene controls the cell cycle is by transactivating p21WAF1/CIP1, a cyclin-dependent kinase (cdk) inhibitor. By inhibiting cdks, p21WAF1/CIP1 blocks the G-1 to S-phase transition in the cell cycle. p53 can be regulated by MDM2 (murine double minute-2) through direct inactivation or promotion of its cytoplasmic degradation. In an attempt to investigate the cell cycle checkpoint mechanisms of these tumors, we studied the expression of p53, Ki-67, MDM2, and p21WAF1/CIP1 by immunohistochemistry. We analyzed the expression of these proteins in 19 cystadenomas (8 serous and 11 mucinous), 40 borderline tumors (31 serous and 9 mucinous), and 18 serous carcinomas of the ovary. p21WAF1/CIP1 was expressed in 7 of 19 (37%) benign cystadenomas, 32 of 40 (80%) borderline tumors (93.5% of serous and 33% of mucinous), and in 9 of 18 (50%) serous carcinomas. Ki-67 was only weakly expressed in 8 of 19 (42%) benign cystadenomas, all borderline tumors showed Ki-67 staining in less than 50% of the cells, and 55% of serous carcinomas stained in more than 50% of tumor cells. p53 was absent in all but 1 of the cystadenomas, was expressed in 9 of 40 (22.5%) borderline tumors (25.8% of serous and 11% of mucinous), and in 10 of 18 (55%) carcinomas. All 11 implants of serous borderline tumors expressed p21WAF1/CIP1. Most serous borderline tumors expressed higher levels of MDM2 compared with the benign cystadenomas and carcinomas. Four of the serous borderline implants (40%) expressed MDM2. Coexpression of p21WAF1/CIP1 and MDM2 characterizes serous borderline tumors of the ovary and their implants, which suggests that these cell cycle control proteins are important in these tumors and may be related to tumor progression. Low expression of p53 protein in serous borderline tumors might be in part mediated by MDM2. This suggests that the p53 pathway is intact in most of these tumors, in contrast with carcinomas, in which high expression of p53 has been related to mutations of this gene.     

Clinicopathological significance of DEK overexpression in serous ovarian tumors

To investigate the significance of DEK protein expression in ovarian lesions, a total of 113 ovarian serous tumors, including 62 serous cystadenocarcinomas and 19 serous borderline tumors, were studied on immunohistochemistry. For comparison, 32 benign serous tumors, including 12 serous papillary cystadenomas, 10 serous cystadenomas, and 10 serous surface papillomas, were also included. DEK was positive in 93.5% of serous cystadenocarcinomas (58/62), 63.2% of serous borderline tumors (12/19), and weakly positive in 15.6% of benign serous tumors (5/32). The strong positive signal was detected only in serous adenocarcinomas (80.6%, 50/62) and borderline tumors (21.1%, 4/19), but no serous benign tumors were strongly positive (0%, 0/32). Meanwhile, the strong positivity rate of DEK protein was significantly higher in grade 2 and grade 3 than in grade 1 ovarian cancers ( P < 0.05), but there was no significant association between DEK protein expression level and International Federation of Gynecology and Obstetrics (FIGO) stage of serous ovarian adenocarcinoma ( P > 0.05). In summary, DEK plays an important role in the progression of ovarian serous cancers. The detection of DEK protein expression should be useful for the diagnosis and prognosis of ovarian serous cancers, and DEK might be a useful molecular target for ovarian cancer therapy.     

卵巢癌中k-ras 基因点突变及p53蛋白表达

目的 探讨k—ras基因点突变和p53蛋白表达在卵巢癌发生中的作用及致癌机制。方法 采用显微切割技术、半巢式PCR—RFLP技术和免疫组化染色检测55例卵巢癌及其交界性病变中的k—ras基因点突变和p53蛋白表达。结果 k-ras基因点突变率在黏液性腺癌(61．9％)明显高于浆液性腺癌(14．2％),在黏液性交界性腺瘤(61．5％)明显高于浆液性交界性腺瘤(12．5％)。p53蛋白表达率在浆液性腺癌(80％)明显高于黏液性腺癌(52％),并随组织学分级而增高。结论 黏液性腺癌主要通过腺瘤-交界性腺瘤-腺癌途径致癌,k—ms基因点突变是黏液性腺癌的早期事件,黏液性交界性腺瘤是黏液性腺癌的癌前病变。浆液性腺癌主要通过生发上皮直接恶性转化形成,p53蛋白表达在浆液性腺癌的发生中起重要作用,是浆液性腺癌的晚期事件。     

Focal adhesion kinase overexpression in endometrial neoplasia.

Focal adhesion kinase (FAK) is a protein tyrosine kinase that is a critical mediator of signaling events between cells and their extracellular matrix. Elevations in FAK mRNA and protein overexpression have been linked to tumor cell capacity for invasion and metastasis. FAK expression has been shown to be elevated in a variety of solid tumors. The purpose of this study was to evaluate for FAK upregulation in endometrial neoplasia. Tissue microarray blocks were made from formalin-fixed, paraffin-embedded archival tissue, including 115 carcinoma (100 endometrioid, 10 serous, and 5 clear cell), 28 hyperplasia, and 38 normal specimens using 1-mm punches. The tissue was immunostained with monoclonal antibody for FAK and p53. Immunoreactivity was scored by intensity (0-4+ scale) and percent positive staining. FAK overexpression was categorized as 4+ cytoplasmic intensity in more than 90% of neoplastic cells. Positive p53 was categorized at least 2+ nuclear intensity in more than 10% of neoplastic cells. Higher rates of FAK upregulation were identified in endometrial hyperplasia (P = 0.025) and carcinoma (P < 0.001) versus normal endometrium. FAK overexpression in carcinoma correlated with higher FIGO grade (P = 0.025) and p53 overexpression (P < 0.001). FAK was consistently overexpressed in high-grade tumors regardless of subtype, including 8 of 10 serous tumors, 4 of 5 clear cell tumors, and 16 of 23 grade 3 endometrioid tumors. In conclusion, upregulation of FAK is seen in both endometrial hyperplasia and carcinoma, implying that FAK may play an important role in endometrial carcinogenesis. FAK overexpression in endometrial carcinoma correlates with higher FIGO grade and p53 overexpression.     

Gross genomic alterations differ between serous borderline tumors and serous adenocarcinomas—an image cytometric DNA ploidy analysis of 307 cases with histogenetic implications

Our objective was to study the gross genomic alterations in serous borderline tumors and serous adenocarcinomas of the ovary. A retrospective analysis of 245 serous borderline tumors and 62 serous adenocarcinomas from 249 patients was performed using high-resolution image cytometric DNA ploidy analysis. DNA ploidy status, S-phase fraction, and DNA index were evaluated. The majority of serous borderline tumors were diploid (225/245 cases, 92%). The remaining 8% showed an aneuploid peak predominantly with DNA index of less than 1.4. Grades 2 and 3 serous adenocarcinomas were more often (80%) nondiploid, mostly with DNA index exceeding 1.4. Grade 1 serous adenocarcinomas were an intermediate group, more similar to serous borderline tumors. The S-phase fraction increased from serous borderline tumors (mean = 0.6%) through grade 1 serous adenocarcinomas (mean = 2.8%), being highest in grades 2 and 3 adenocarcinomas (mean = 6.8%). Our findings support the hypothesis that serous borderline tumors and grades 2 and 3 serous adenocarcinomas are genomically different lesions, with grade 1 serous adenocarcinomas being an intermediate group more close to borderline tumors.     

Human papilloma virus (HPV) status, p16INK4a, and p53 overexpression in epithelial malignant and borderline ovarian neoplasms

This investigation is the first to evaluate simultaneously human papilloma virus (HPV) status, p16(INK4a), and p53 immunoreactivity in epithelial ovarian neoplasms. The results were analyzed and correlated with histological type, histological grade, and survival of patients. Subtypes considered are papillary serous and mucinous. Polymerase chain reaction (PCR) analysis, performed in our previous study, had already demonstrated a small number of HPV-positive epithelial ovarian neoplasms. No significant correlation was found between the presence of HPV DNA and subtypes of ovarian neoplasms; thus, HPV cannot be considered responsible for epithelial ovarian neoplasm. Since p16 immunoreactivity was present in many other HPV-negative cases of epithelial ovarian neoplasms, this study suggests that p16 overexpression in some neoplasms of the female genital tract is not related to HPV carcinogenesis. A higher p53 expression rate observed between borderline and malignant serous tumors and between serous and mucinous neoplasms can confirm a recent dualistic model of ovarian carcinogenesis. According to this theory, low-grade serous carcinomas (serous intraepithelial carcinomas, serous borderline neoplasm, and ovarian mucinous neoplasms) (type I tumors) develop from mutations of KAS and BRAF, while high-grade serous carcinomas (type II tumors) develop from mutation of p53. In malignant neoplasms, for univariate analysis, patient survival seems to be related to p53, strong and diffuse p16 overexpression, and the stage of development of neoplasms at the diagnosis. In multinomial logistic regression, used to evaluate the role of staging, grading, p16 and p53 immunopositivity as predictor variables of unfavorable outcome of the disease, only p16 positivity was significantly related to the poor prognosis of the cancer.     

DNA fragmentation factor (DFF45): expression and prognostic value in serous ovarian cancer

This study investigated the expression of DNA fragmentation factor (DFF45), MIB-1, and p53 in formalin-fixed, paraffin-embedded archival tissues of 50 ovarian serous carcinomas. In addition, 10 benign serous cystadenomas and 10 serous neoplasms of low malignant potential (LMP) were included in this DFF45 immunostudy. With regard to quantity and intensity of positively stained cells, immunostaining for DFF45 was scored as low or strong. MIB-1 labeling indexes (LIs) were quantitated as the percentage of positively stained nuclei in 1000 nuclei. For p53, at least 10% of tumor cells had to display nuclear staining to consider a case positive. DFF45 staining was noted predominantly in the nucleus. Low DFF45 expression was identified in all serous cystadenomas and in LMPs, as well as in 18 (36%) ovarian serous carcinomas. The latter displayed strong expression in 32 cases (64%). DFF45 immunoreactivity increased with FIGO stage and with grade (P=0.0213 and 0.0084, respectively), as well as with p53 positivity (P=0.04), but not with MIB-1 LIs (P=0.076). A trend towards poor outcome was observed in patients whose tumors displayed high levels of DFF45 immunoexpression (P=0.0187). Apoptotic bodies were consistently DFF45-negative. This study indicates that DFF45 expression is frequently upregulated in ovarian serous carcinomas and may serve as a marker of aggressive behavior with prognostic value.     

Immunohistochemical profile of endometrial adenocarcinoma: a study of 61 cases and review of the literature.

The differences in immunohistochemical expression of p53, bcl-2, bax, estrogen receptor (ER), and progesterone receptor (PR) were evaluated in 40 endometrioid and 21 papillary serous carcinomas of endometrium and correlated with known predictors of survival, such as grade and stage. Uterine papillary serous adenocarcinomas (UPSA) showed significantly higher p53 expression than did uterine endometrioid adenocarcinomas (UEA) (76.2% versus 35%), whereas both ER and PR were more often positive in endometrioid than in serous tumors (p = .005 and .0005). No significant difference was found in bcl-2 and bax expression between both histologic types. However, there was definite decrease in intensity of bcl-2 in UPSA compared with UEA. In endometrioid carcinoma, p53 overexpression was associated with high-grade and advanced-stage tumors (p = .0006 and .006), whereas ER and PR expression was associated with low-grade and early-stage tumors (p = .0006 and .0001; p = .003 and .0006). Bcl-2 immunopositivity was more common in low-grade, early-stage rather than in high-grade, advanced-stage adenocarcinomas, but the difference was not statistically significant (p = .24 and .07). Bax immunopositivity was associated with well-differentiated (p = .04) and early-stage tumors. Furthermore, a significant inverse relationship between bax and p53 reactivity was defined (p = .05), especially in tumors of endometrioid type. Bax and PR immunoexpression correlated near the limit of statistical significance (p = .08), whereas no relationship was found among bax, bcl-2, and ER immunopositivity. Our results indicate that the differences in immunohistochemical profiles of endometrioid and serous carcinomas support the existence of different molecular pathways of their development. The correlation of immunohistochemical findings with histologic grade and clinical stage could help in predicting biologic behavior and planning treatment in patients who are diagnosed as having these tumors.