蛋白酪氨酸激酶PTK7在卵巢浆液性肿瘤中的表达及意义

背景与目的：新近发现的蛋白酪氨酸激酶-7(protein tyrosine kinase-7,PTK7)基因与多种肿瘤的发生、发展和浸润有关。本研究旨在探讨PTK7在卵巢浆液性肿瘤中的表达及其与临床分期、组织学分级、转移和预后等指标的关系,分析PTK7表达在卵巢浆液性肿瘤中的诊断及预后价值。方法：制备3株卵巢癌细胞系(HO8910、SKOV3、A2780)爬片,并收集14例正常输卵管上皮组织,6例良性浆液性卵巢肿瘤,51例交界性浆液性卵巢肿瘤和97例卵巢浆液性癌组织蜡块,采用免疫组化EliVision两步法检测PTK7蛋白的表达,结合相关病理指标,采用χ²检验、Fisher确切概率法、Kaplan-Meier法进行统计分析。结果：PTK7在卵巢癌细胞株HO8910及A2780中呈阴性表达,在SKOV3中成弱阳性表达。PTK7在92.86%(13/14)的正常输卵管上皮、83.33%(5/6)的良性浆液性卵巢肿瘤、45.10%(23/51)的交界性浆液性卵巢肿瘤和28.87%(28/97)的浆液性卵巢癌中阳性表达。正常输卵管上皮与良性浆液性肿瘤、良性浆液性肿瘤与交界性浆液性肿瘤之间PTK7表达差异无统计学意义(P=0.521,P=0.102)。浆液性卵巢癌与正常输卵管上皮、良性浆液性肿瘤以及交界性浆液性肿瘤之间PTK7表达差异有统计学意义(P=0.000,P=0.012,P=0.048)。PTK7在交界性浆液性卵巢肿瘤中的表达与其临床分期、淋巴结和(或)腹膜转移情况有关(P=0.038,P=0.038),与其发生部位、年龄无关(P=0.088,P=0.896)。PTK7在卵巢浆液癌中的表达与其临床分期、WHO分级、MDACC病理分级有关(P=0.011,P=0.004,P=0.000),与其发生部位、转移情况、肿瘤直径、年龄无关(P=0.326,P=0.524,P=0.588,P=0.584)。卵巢浆液癌中PTK7阳性组的生存率显著高于阴性组(P=0.017)。结论：PTK7在输卵管正常上皮、良性浆液性卵巢肿瘤、交界性浆液性卵巢肿瘤和浆液性癌中表达呈逐步下调趋势。PTK7表达与卵巢上皮性浆液性肿瘤的较晚临床分期、高组织分级、预后差呈正相关,可能成为卵巢浆液性肿瘤辅助诊断及临床预后的新指标。     

E-cadherin、VEGF蛋白在卵巢浆液性交界性肿瘤中的表达及其生物学意义

目的:探讨卵巢浆液性交界性肿瘤(sBOT)中E-钙黏附素(E-cadherin)和血管内皮生长因子(VEGF)的表达特点及临床病理意义.方法:采用免疫组化技术检测E-cadherin和VEGF在良性卵巢浆液性肿瘤、卵巢浆液性交界性肿瘤和卵巢浆液性恶性肿瘤中的表达特点,分析与sBOT临床病理指标的相关性.结果:E-cadherin在良性卵巢、交界性卵巢和恶性卵巢组织中表达呈下降趋势(P＜0.01),而VEGF在各组表达呈明显上升趋势(P＜0.01),两者存在负相关性.E-cadherin和VEGF在sBOT和低级别卵巢恶性肿瘤中表达无明显差异(P＞0.05).VEGF高表达与sBOT病理亚型、浸润性病灶和sBOT临床分期有关(P＜0.05).E-cadherin低表达与sBOT病理亚型、浸润性病灶有关(P＜0.05).结论:E-cadherin低表达或缺失和VEGF高表达与卵巢浆液性肿瘤的良恶性有关,联合检测可为卵巢交界性肿瘤预后判断提供依据.VEGF表达与sBOT的预后、转移关系密切.     

24例卵巢交界性上皮性肿瘤的临床及病理分析

目的：探讨卵巢上皮性交界性肿瘤的病理学改变、临床分期及手术范围对预后的影响、方法：分析1975年至1992年卵巢交界性上皮性肿瘤24例的临床资料、病理及随访结果。结果：24例中浆液性8例.粘液性15例,混合性1例。临床Ⅰ期14例、Ⅱ期5例、Ⅲ期5例。现22例存活（占92％）,2例死了肿瘤并发症肠梗阻。结论：提示细致的病理分析是诊断交界性上皮性肿瘤的关键预后与手术方式及化疗关系不密切而与肿瘤分期及术后有无肿瘤残存有关;对肿瘤复发的病例多次手术治疗是必要的。     

卵巢交界性肿瘤的治疗（附21例临床分析）

本研究分析２０年间，我院２１例卵巢交界性肿瘤的临床、病理特，点及治疗与预后的关系。其中粘液性交界性上皮肿瘤１１例（４７．６２％），浆液性交界性上皮瘤８例（３８。１％），其他类型３例（１４．２８％）。卵巢浆液性交界性肿瘤患者的平均年龄低于粘液性肿瘤。并发现前者双侧发生率较高。Ⅱ期、Ⅲ期病人的５年存活率明显低于Ⅰ期。手术治疗是最重要的方法，并且术后应长期随访。     

核转录因子E2F2在卵巢浆液性肿瘤组织中的表达及其临床意义

目的:探讨核转录因子E2F2在卵巢浆液性肿瘤组织中的表达及其临床意义.方法:采用免疫组化SP法检测33例卵巢浆液性囊腺癌、11例卵巢交界性浆液性囊腺瘤、13例卵巢浆液性囊腺瘤以及12例正常卵巢组织中E2F2蛋白的表达.结果:E2F2蛋白在卵巢浆液性囊腺癌、交界性浆液性囊腺瘤、浆液性囊腺瘤以及正常卵巢组织中的阳性表达率分别为72.73%(24/33)、54.55%(6/11)、15.38(2/13)%和8.3%(1/11),E2F2蛋白在卵巢浆液性囊腺癌组织、交界性浆液性囊腺瘤组织中的阳性表达率明显高于在浆液性囊腺瘤、正常卵巢组织中的阳性表达率(P均＜0.05),卵巢浆液性囊腺癌组的阳性表达率值虽然高于交界性浆液性囊腺瘤组,但是两组之间差异无统计学意义(P＞0.05),浆液性囊腺瘤的阳性表达率接近正常卵巢组的2倍,但是两组之间的阳性表达率差异也无统计学意义(P＞0.05);在卵巢浆液性囊腺癌组织中,E2F2蛋白的阳性表达率随手术病理分期的增加而增加(P＜0.05), 但与病理分级以及有无淋巴结转移无关( P均＞0.05);在卵巢浆液性囊腺癌组织中,E2F2蛋白的表达水平随手术病理分期的增加、病理分级降低而增加(P均＜0.05),与有无淋巴结转移无关(P＞0.05).结论:在卵巢浆液性囊腺癌组织、交界性浆液性囊腺瘤组织中核转录因子E2F2呈现明显的高表达,且其表达水平与手术分期、病理分级相关,提示E2F2在卵巢癌的发生发展中起到促进作用.     

卵巢浆液性肿瘤PTTG的表达与MMP-2 及VEGF的关系*

目的:研究垂体肿瘤转化基因（PTTG）蛋白、基质金属蛋白酶-2（MMP-2）、血管内皮生长因子（VEGF）在卵巢浆液性肿瘤中的表达及其相关性,探讨PTTG在卵巢浆液性肿瘤恶性转化中的作用及与肿瘤侵袭性的关系。方法:运用免疫组织化学的方法检测30例卵巢浆液性囊腺瘤、21例卵巢交界性浆液性囊腺瘤、30例卵巢浆液性囊腺癌原发灶和网膜转移灶中PTTG、MMP-2及VEGF的表达水平。结果:1）PTTG在卵巢浆液性肿瘤各分组中表达差异有统计学意义（P<0.01）,其中交界性浆液性囊腺瘤组的表达高于浆液性囊腺瘤组（P<0.01）,浆液性囊腺癌原发灶组表达高于交界性组（P<0.01）,浆液性囊腺癌网膜转移灶组表达高于原发灶组（P<0.05）;2）MMP-2 在浆液性囊腺癌原发灶组及交界性浆液性囊腺瘤组中的表达高于浆液性囊腺瘤组（P<0.01）,在浆液性囊腺癌网膜转移灶中的表达高于原发灶组（P<0.05）;3）VEGF在浆液性囊腺癌原发灶组及交界性浆液性囊腺瘤组中的表达高于浆液性囊腺瘤组（P<0.05）,在浆液性囊腺癌网膜转移灶组与原发灶组间表达差异无统计学意义（P>0.05）;4）PTTG、MMP-2和VEGF三者的表达水平呈正相关（P<0.01）。 结论:PTTG表达程度随卵巢浆液性肿瘤恶性程度及侵袭性的增加而升高,PTTG可能参与了卵巢浆液性肿瘤恶性转化过程并且通过上调MMP-2 及VEGF的表达在肿瘤侵袭转移中发挥重要作用。      

TMEFF1在卵巢上皮性浆液性肿瘤中的表达及其临床意义

目的:检测TMEFF1(tomoregulin-1)在卵巢上皮性浆液性肿瘤中的表达,探讨其临床意义.方法:采用免疫组化SP法检测卵巢上皮性浆液性囊腺癌、卵巢上皮性交界性肿瘤、卵巢上皮性良性肿瘤以及正常卵巢组织中TMEFF1的表达情况,分析其与卵巢上皮性浆液性囊腺癌临床病理参数及预后的关系.结果:TMEFF1以胞膜着色为主,亦有胞浆着色.TMEFF1在卵巢上皮性浆液性囊腺癌中的表达率(90.24%)明显高于卵巢上皮性交界性肿瘤(45.45%)、卵巢上皮性良性肿瘤(33.33%)及正常卵巢(26.67%) (P均<0.05).在卵巢上皮性浆液性囊腺癌中,TMEFF1表达随FIGO分期增加而逐渐增加(P<0.05),TMEFF1为影响卵巢上皮性浆液性癌预后的独立危险因素(P<0.05).结论:TMEFF1的表达与卵巢癌的发生、发展及预后相关.     

B7-H4在卵巢浆液性癌组织中的表达及其临床意义

目的探讨B7-H4在卵巢上皮性肿瘤浆液性癌中的表达情况及其临床意义。方法应用逆转录聚合酶链反应(RT-PCR)技术及采用免疫组织化学PV-9000二步法,检测40例卵巢浆液性癌、20例交界性卵巢浆液性肿瘤和15例卵巢浆液性囊腺瘤组织中B7-H4mRNA及B7-H4蛋白表达情况。结果 B7-H4mRNA在卵巢浆液性癌、交界性卵巢浆液性肿瘤和卵巢浆液性囊腺瘤组织中均有表达;B7-H4蛋白表达于卵巢浆液性肿瘤细胞胞质和(或)胞膜,卵巢浆液性癌、交界性卵巢浆液性肿瘤和卵巢浆液性囊腺瘤组织中其阳性表达率分别为75.0%(30/40)、50.0%(10/20)和13.3%(2/15),阳性率逐级下降,差异均有统计学意义(P<0.05)。B7-H4蛋白表达与卵巢浆液性癌临床分期、病理分级、患者年龄、腹腔积液细胞学和淋巴结转移无相关性(P>0.05)。结论 B7-H4在卵巢浆液性癌组织中高表达,提示其可能与肿瘤的发生发展有关,可为卵巢恶性肿瘤的诊断及治疗提供新策略。     

原发性腹膜浆液性交界性肿瘤1例报道及文献复习

目的:探讨原发性腹膜浆液性交界性肿瘤（primary peritoneal serous borderline tumor,PPSBT）的临床表现、鉴别诊断、临床诊治方法和预后。方法:报道1例原发性盆底腹膜浆液性交界性肿瘤（低度恶性）的临床诊治经过、术中发现、病理学特征及免疫组化特点,复习相关文献。结果:术中探查见盆底腹膜表面、直肠前壁浆膜面、子宫表面及卵巢表面见弥漫粟粒样小结节,较大者直经约0.3cm,灰白色。术后证实为盆底腹膜浆液性交界性肿瘤伴腹膜、子宫外膜及卵巢表面广泛种植（低度恶性）。结论:原发性腹膜浆液性交界性肿瘤为低度恶性肿瘤,预后较好。首选手术治疗,对年轻的患者,建议保留子宫及卵巢。术后放化疗被认为不可取。     

WT1与P53在卵巢浆液性癌中的表达及意义

目的 检测WT1和P53在卵巢浆液性肿瘤中的表达,探讨其临床病理学意义及二者的关系.方法 采用免疫组化Envision二步法检测在卵巢良性浆液性肿瘤、交界性浆液性肿瘤和浆液性癌各40例中的WT1和P65表达情况,分析其表达水平与卵巢浆液性癌中临床病理特征的关系.结果 WT1在卵巢良性浆液性肿瘤、交界性肿瘤和浆液性癌中阳...     

Common epithelial tumors of borderline malignancy (carcinomas of low malignant potential)

The creation of the category of ovarian borderline tumors has been a step forward in classification because it has segregated from the general group of common epithelial cancers a subgroup with an unusually good prognosis. Of all borderline tumors, the serous variety is the least difficult for the pathologist to diagnose. The mucinous borderline tumor is not as easy to recognize when an absence of invasion is used as the sole diagnostic criterion, but evaluation of other architectural as well as cytological features is helpful in making the diagnosis. Although the treatment of the majority of serous and mucinous borderline tumors is well standardized, therapy of residual serous borderline tumor is highly controversial and the treatment for pseudomyxoma peritonei, unsatisfactory. Borderline tumors exist in the endometrioid, clear cell, Brenner, and mixed common epithelial categories, but these tumors have been too rare to date in order to clearly characterize their clinical and pathological features. It is hoped that more can be learned about this general group of tumors by a more widespread recognition of their distinctive clinico-pathologic features and by their acceptance as a special subgroup of ovarian cancer. Their behavior differs strikingly from that of other types of malignant ovarian tumors and it is clear that their management should differ accordingly.     

Association of Reproductive Factors, Oral Contraceptive Use and Selected Lifestyle Factors with the Risk of Ovarian Borderline Tumors: A Danish Case-control Study

Objective The aim was to examine risk factors for ovarian borderline tumors overall, and according to histological subtype (serous vs. mucinous), in a large Danish population-based case-control study. Methods Ovarian borderline cases and controls were recruited from 1995 to 1999, and personal interviews were conducted. In all, 202 cases and 1,564 randomly selected controls were included. The analysis was performed using multiple logistic regression models. Results The risk of ovarian borderline disease decreased with increasing parity (OR=0.79 per birth, 95% CI: 0.63–0.98) and older age at first birth (OR=0.67 per 5 years, 95% CI: 0.53–0.84). Both a history of breastfeeding and use of oral contraceptives reduced the risk of borderline tumor, the effect being most pronounced for serous tumors. Increasing body mass index (BMI) was associated with elevated risk of serous borderline tumor (OR=1.05 per BMI unit; 95% CI: 1.00–1.10), whereas current smoking was a strong risk factor only for mucinous tumors (OR=2.10; 95% CI: 1.22–3.60). Finally, increasing consumption of milk (all types) was found to increase the risk of borderline disease (OR=1.04 per glass milk per week; 95% CI: 1.02–1.06), and increasing intake of total lactose also increased the risk significantly (OR=1.16 per 50 gram lactose per week; 95% CI: 1.06–1.26). Conclusion The risk profile of ovarian borderline tumors is similar to that of ovarian carcinomas, and we observed significant etiological differences between serous and mucinous borderline tumors.     

Immunohistochemical staining of GLUT1 in benign, borderline, and malignant ovarian epithelia

BACKGROUND: Aberrant expression of the facilitative glucose transporter GLUT1 is found in a wide spectrum of epithelial malignancies. The authors describe an immunohistochemical study of GLUT1 expression in benign, borderline, and malignant ovarian epithelia. METHODS: One hundred forty one formalin-fixed, paraffin-embedded sections were immunostained with rabbit anti-GLUT1 using the streptavidin-biotin method. The samples were as follows: 3 endometriotic cysts, 9 serous cystadenomas, 15 mucinous cystadenomas, 17 noninvasive borderline implants, 3 invasive borderline implants, and 3 endosalpingiosis. In addition, 35 borderline tumors (26 serous, 7 mucinous, 2 seromucinous) and 56 adenocarcinomas (50 serous, 4 endometrioid, 2 mucinous) were stained. RESULTS: Benign serous and mucinous cystadenomas and endosalpingiosis were non-staining with GLUT1 antiserum. Twenty-eight of 35 borderline tumors (80%) stained positively, with weak to moderate (1-2+ out of 3) staining intensity and focal or patchy distribution. Seventeen noninvasive serous borderline implants were negatively stained; however, three invasive serous borderline implants were positively stained with GLUT1 antiserum. Fifty four of 56 ovarian carcinomas (96%) stained positively, with moderate to strong (2-3+ out of 3) intensity and multifocal distribution. CONCLUSIONS: GLUT1 is a consistent marker of ovarian epithelial malignancy. GLUT1 staining is absent in benign ovarian epithelial tumors, and shows progressively more staining in invasive tumors as compared to borderline tumors. Anti-GLUT1 antibody may be useful in distinguishing invasive from noninvasive serous borderline implants.     

Borderline ovarian tumour: pathological diagnostic dilemma and risk factors for invasive or lethal recurrence

By comparison with ovarian carcinomas, borderline ovarian tumours are characterised clinically by superior overall survival, even in women with peritoneal spread. In this Review, we aimed to clarify the histological and clinical factors potentially defining a high-risk group in whom disease is likely to evolve to invasive disease. Invasive peritoneal implants (in serous borderline ovarian tumours) and residual disease after surgery were the two factors clearly identified. Other factors are controversial owing to increased risk of invasive recurrence: micropapillary patterns in serous borderline ovarian tumour, intraepithelial carcinoma in mucinous lesions, stromal microinvasion in serous lesions, and use of cystectomy in mucinous borderline ovarian tumours. The pathologist has a pivotal role in assessment of the borderline nature of ovarian tumours and in identification of high-risk criteria, most of which are histological. But, reproducibility of the histological interpretation of some of these potential criteria--eg, classification of peritoneal implants (particularly in desmoplastic subtype), stromal microinvasion, micropapillary patterns, and intraepithelial carcinoma in mucinous borderline ovarian tumours--remains unclear, and should be investigated.     

Expression of pro-apoptotic (p53, p21, bax, bak and fas) and anti-apoptotic (bcl-2 and bcl-x) proteins in serous versus mucinous borderline ovarian tumours

BACKGROUND: We examined the expression of apoptosis-related proteins in serous versus mucinous borderline ovarian tumours, in comparison with benign and malignant ovarian tumours. MATERIALS AND METHODS: Immunohistochemical expression of pro-apoptotic (p53, p21, bax, bak, fas) and anti-apoptotic proteins (bcl-2, bcl-x) was determined in 34 borderline (19 mucinous, 15 serous), 20 benign (10 mucinous, 10 serous) and 28 malignant ovarian tumours (9 mucinous, 19 serous). RESULTS: A difference in semi-quantitative p53 expression was found between benign and borderline tumours (P = 0.01), but not between borderline and malignant tumours. Increased p21 expression was found in borderline versus benign tumours (P = 0.004). Bcl-2 expression was lower in borderline than in benign (P = 0.01) and malignant tumours (P = 0.02). No difference in bax, bak, fas or bcl-x expression was observed among the three tumour types. Higher percentage of p21 positive cells was found in serous than in mucinous borderline tumours (P < 0.001). Bcl-2 expression was higher in serous than in mucinous forms of benign (P < 0.001), borderline (P < 0.001), and malignant tumours (P < 0.003). No difference in p53, bax, bak, fas or bcl-x expression was observed between serous and mucinous borderline ovarian tumours. CONCLUSION: Although p53 overexpression was a common feature of both mucinous and serous borderline tumours, p21 and bcl-2 overexpression appeared specific to serous tumours.     

Molecular Characterization of 103 Ovarian Serous and Mucinous Tumors

The pathogenesis of ovarian carcinomas is heterogeneous, with even the same entities showing great variance. In our study we investigated the mutations of the BRAF, KRAS, and p53 genes in serous and mucinous borderline tumors and in low grade and high grade serous and mucinous tumors. The mutations of BRAF and KRAS genes have been shown in 60% of borderline and low grade (well differentiated) serous and mucinous tumors, but very rarely in high grade (moderately and poorly differentiated) carcinomas. However mutations of p53 are very common in high grade tumors and this indicates a "dualistic" model of ovarian tumorigenesis. A total of 80 serous tumors, including serous borderline, low grade and high grade tumors, and 23 mucinous tumors, including borderline and invasive tumors were analysed for BRAF and KRAS mutations using real time PCR method followed by melting point analysis. P53 mutation was investigated by immunohistochemistry. We assumed mutation of the p53 gene when 100% of tumor cells showed strong nuclear positivity. We observed differences in genetic alterations in the development of the low grade tumors and between low and high grade tumors too. In some bilateral or stage II-III cases we observed differences between the mutation status of the left and right ovarian tumors and between the primary tumor and its implants. In one case in a tumor with micropapillary pattern showing high grade nuclear atypia we could detect mutations in both KRAS and p53 genes. The majority of our mucinous ovarian tumor cases showed a KRAS mutation. We have not found mutations of the BRAF and p53 genes in these cases. We have found as have others, that there is a dualistic pathway of ovarian carcinogenesis. In the majority of cases, low grade epithelial tumors develop in a stepwise manner due to genetic alterations of the members of MAP-kinase pathway; however mutation of the p53 gene is the key event in the development of high grade tumors.     

端粒酶反转录酶与CA125在卵巢上皮性肿瘤组织中的原位表达及临床意义

目的:探讨端粒酶反转录酶(TRT)与CA125在卵巢上皮性肿瘤组织中的原位表达及临床意义。方法:收集93例卵巢上皮性肿瘤(良性47例、交界性15例、恶性31例),应用免疫组织化学S蛳P法检测肿瘤组织中TRT及CA125的原位表达,将结果进行统计学分析。结果:TRT的表达在良性(17.02%,8/47)和交界性(46.67%,7/15)以及恶性(90.32%,28/31)间的差异均有显著性意义(P<0.01);CA125的表达在良性(23.40%,11/47)和恶性(67.74%,21/31)间的差异有显著性意义(P<0.01),TRT的表达在浆液性肿瘤与黏液性肿瘤之间差异无显著性意义(P>0.05);CA125在各组浆液性肿瘤均明显高于黏液性肿瘤组,相比较差异有显著性意义(P<0.05);TRT和CA125在浆液性肿瘤的表达有一致性,相关性分析有显著性相关(P<0.01),在黏液性肿瘤中表达不相关(P>0.05)。结论:TRT和CA125的表达与卵巢上皮组织肿瘤的良恶性有关,尤其在卵巢浆液性肿瘤中TRT酶的活性与CA125呈正相关,二者的共同检测对诊断卵巢上皮组织肿瘤的类型和恶性程度有重要的临床意义。     

Alteration of BRCA-1 tumor suppressor gene expression in serous and mucinous ovarian neoplasms in the benign-borderline-malignant pathway

Alteration of expression of the tumor suppressor gene BRCA-1 has been widely studied in breast and ovarian carcinoma. However, pattern of this alteration in the benign-borderline-carcinoma sequence in serous and mucinous ovarian neoplasms have not yet fully described. Tissue sections from 214 formalin-fixed paraffin-embedded ovarian specimens were stained immunohistochemically with BRCA-1 antibody. Specimens were 10 normal ovarian surface epithelium, 10 fallopian tube epithelium, 70 benign adenoma (50 serous and 20 mucinous), 28 borderline (13 serous and 15 mucinous), 78 carcinoma (58 serous and 20 mucinous), and 18 metastatic deposit (13 serous and 5 mucinous). Expression was evaluated into 0, +1, +2, and +3. Score +3 staining similar to normal tissues was considered normal and other scores were considered altered expression. Strong expression was seen in all normal epithelium specimens. Altered expression was seen in 34 serous neoplasms; 17 of 50 (34%) of benign cystadenomas, 6 of 13 (46%) of borderline tumors, 43 of 58 (74%) of primary carcinoma, and in 8 of 13 (62%) of metastatic carcinoma. This alteration was significantly associated with higher histopathologic grade (P = 0.049), presence of necrosis (P = 0.0001), and higher proliferation rate (P = 0.001). In mucinous neoplasms; altered BRCA-1 was detected in 25 specimens; 7 of 20 (41%) of benign cystadenomas, 5 of 15 (33%) of borderline neoplasms, 9 of 20 (45%) of primary carcinoma, and 4 of 5 (80%) of the metastatic deposits. This alteration was not associated with any of the clinicopathologic tumor characteristics. In conclusion, alteration of BRCA-1 expression is more frequent in serous than in mucinous carcinomas and is associated with tumors of higher grades and high proliferation rate.     

MDM2 Expression in Serous and Mucinous Epithelial Tumours of the Ovary

Background: Different types of cancer exhibit abnormalities in cell cycle regulators. The murine double minute2(MDM2) cell cycle regulator is a protooncogene that negatively regulates the P53 tumour suppressor gene. Surface epithelial tumours constitute approximately two thirds of ovarian neoplasms. Each histologic type can be classified as benign, borderline and malignant. This study aimed to examine immunohistochemical expression of the MDM2 protein in ovarian serous and mucinous epithelial tumours (benign, borderline and malignant). Materials and Methods: This study included forty five ovarian tumours, subdivided into fifteen cystadenomas (5 serous and 10 mucinous), fifteen borderline tumours (11 serous and 4 mucinous) and fifteen cystadenocarcinomas (9 serous and 6 mucinous). Paraffin sections were stained with haematoxylin and eosin for histopathologic study, and with mouse monoclonal antiMDM2 antibody for immunohistochemistry. Results: MDM2 positivity was detected in 28.9% of the studied ovarian tumours. All benign tumours were negative and positivity was significantly higher in malignant than borderline tumours (P value of chisquare test 0.000). Significantly, all MDM2 positive mucinous tumours were malignant with no positive mucinous borderline tumours. Malignant tumours showed positive MDM2 expression in 83.3% of mucinous type and in 55.6% of serous type. Borderline serous tumours showed negative MDM2 in 72.7% of cases (P value of Z test 0.04). Conclusions: Alterations in the expression of the cell cycle regulator (MDM2) occur early in the process of tumourigenesis in serous and mucinous ovarian tumours. We suggest that MDM2 may be used in those tumours as a marker for risk stratification and identification of cases with cancer development and progression. We recommend further studies on MDM2 immunohistochemistry, in conjunction with adjuvant methods as DNA ploidy and FISH gene amplification, focusing on the mucinous tumours and differentiating between the three tumour categories, benign, borderline and malignant.