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.     

Expression profiling of serous low malignant potential, low-grade, and high-grade tumors of the ovary

Papillary serous low malignant potential (LMP) tumors are characterized by malignant features and metastatic potential yet display a benign clinical course. The role of LMP tumors in the development of invasive epithelial cancer of the ovary is not clearly defined. The aim of this study is to determine the relationships among LMP tumors and invasive ovarian cancers and identify genes contributing to their phenotypes. Affymetrix U133 Plus 2.0 microarrays (Santa Clara, CA) were used to interrogate 80 microdissected serous LMP tumors and invasive ovarian malignancies along with 10 ovarian surface epithelium (OSE) brushings. Gene expression profiles for each tumor class were used to complete unsupervised hierarchical clustering analyses and identify differentially expressed genes contributing to these associations. Unsupervised hierarchical clustering analysis revealed a distinct separation between clusters containing borderline and high-grade lesions. The majority of low-grade tumors clustered with LMP tumors. Comparing OSE with high-grade and LMP expression profiles revealed enhanced expression of genes linked to cell proliferation, chromosomal instability, and epigenetic silencing in high-grade cancers, whereas LMP tumors displayed activated p53 signaling. The expression profiles of LMP, low-grade, and high-grade papillary serous ovarian carcinomas suggest that LMP tumors are distinct from high-grade cancers; however, they are remarkably similar to low-grade cancers. Prominent expression of p53 pathway members may play an important role in the LMP tumor phenotype.     

Overexpression and diffuse expression pattern of IQGAP1 at invasion fronts are independent prognostic parameters in ovarian carcinomas

IQGAP1 is a multifunctional protein involved in actin cytoskeleton assembly and E-cadherin-mediated cell adhesion. To determine the role of IQGAP1 in ovarian tumors, we evaluated IQGAP1 expression by immunohistochemistry in 17 adenomas, 30 borderline tumors and 80 adenocarcinomas and its relation with patient survival. IQGAP1 was overexpressed in adenocarcinomas compared with adenomas and borderline tumors. Enhanced immunostaining in invasive tumor fronts was categorized as focal or diffuse. The diffuse expression pattern correlated with high histological grade and clinicopathological stages. IQGAP1 overexpression and diffuse invasion pattern were significantly associated with poor prognosis by multivariate analysis. Our findings suggest the involvement of IQGAP1 in the progression and spread of ovarian adenocarcinomas. Overexpression and diffuse expression pattern of IQGAP1 are potentially useful independent molecular predictors of highly aggressive ovarian carcinomas.     

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。     

卵巢浆液性癌发生过程中ARHI STAT3和E2F1蛋白表达的变化及意义

目的 研究卵巢浆液性癌由增生到癌变过程中,ARHI、STAT3和E2F1蛋白表达的变化规律及意义.方法 采用免疫组化法,检测25例正常卵巢上皮组织、35例卵巢浆液性囊腺瘤、18例卵巢交界性浆液性囊腺瘤和56例卵巢浆液性囊腺癌的石蜡包埋组织中,ARHI、STAT3和E2F1蛋白的表达,分析3种蛋白表达与卵巢浆液性癌临床病理特征的关系.结果 在25例正常卵巢上皮和35例浆液性囊腺瘤组织中,分别有22例和30例ARHI蛋白阳性表达,而在18例交界性囊腺瘤和56例浆液性囊腺癌组织中,只有10例和22例阳性表达,ARHI在浆液性癌和交界性囊腺瘤中的阳性表达率(39.3%和55.6%)明显低于其在正常卵巢和浆液性囊腺瘤中的表达(P<0.05).浆液性囊腺癌和交界性囊腺瘤组织中,STAl3蛋白的表达增强,其阳性表达率分别为87.5%(49/56)和77.8%(14/18),明显高于其在正常卵巢和卵巢浆液性囊腺瘤中的表达率(P<0.05).与正常卵巢、卵巢浆液性囊腺瘤和交界性囊腺瘤比较,卵巢浆液性癌中E2F1蛋白表达升高,阳性表达率为82.1%(46/56),明显高于前三者(P<0.05).统计分析显示,ARHI与STAT3和E2F1在卵巢浆液性癌中的蛋白表达呈显著的负相关关系.结论 抑癌印迹基因ARHI的蛋白表达在卵巢浆液性癌中存在不同程度的降低或缺失,而STAT3和E2F1蛋白的表达明显增强,三者可能相互协同,在卵巢浆液性肿瘤的发生中发挥重要作用.     

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.     

Pathology of ovarian carcinoma

Serous carcinoma is the most common type of ovarian cancer and usually is associated with peritoneal metastases and poor survival except for meticulously staged patients with tumors confined to the ovaries. Endometrioid and clear cell carcinomas account for most nonserous carcinomas and more often present with low-stage disease; survival for the various cell types is similar when stratified by stage. Borderline ovarian tumors can be subdivided into benign and malignant neoplasms, and in the view of some experts, this renders the borderline category obsolete. Women with typical serous borderline tumors (atypical proliferative serous tumors) constitute most of these patients and have virtually 100% survival, unless invasive peritoneal implants are present. Micropapillary serous carcinomas (a less common variant, also called serous borderline tumor with a micropapillary pattern) and tumors with invasive implants behave similar to low-grade invasive carcinomas.     

Alteration of the p53 Tumor Suppressor Gene Occurs Independently of K-ras Activation and More Frequently in Serous Adenocarcinomas than in Other Common Epithelial Tumors of the Human Ovary

To clarify the role of the p53 tumor suppressor gene in the development of human ovarian epithelial tumors and to study the association of p53 alterations with K-ras activation, a series of 70 common epithelial ovarian tumors from Japanese patients was studied. These included 31 serous adenocarcinomas, 12 mucinous adenocarcinomas, 5 mutinous tumors of borderline malignancy, 13 endometrioid adenocarcinomas, and 9 clear cell carcinomas. Allelic loss, recognized at the polymorphic site in codon 72 of the p53 gene, was detected in 14 of 36 (39%) informative cases by restriction fragment length polymorphism analysis and by single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction(PCR)-amplified DNA fragments. Mutations in the highly conserved regions of the p53 gene were detected by SSCP analysis of PCR-amplifled fragments. Mutations were found in 22 of 70 (31%) ovarian tumors, including 1 of 5 mucinous tumors of borderline malignancy. Mutations were subsequently characterized by direct sequencing. Single missense base substitutions were detected in 13 ovarian carcinomas and in one case of mucinous tumor of borderline malignancy. Short (1-8 bp) deletions and insertions were found in 8 cases. Mutations in the p53 gene occurred more frequently in serous adenocarcinomas (14/31, 45%) than in all nonserous types of malignant epithelial tumors combined (7/34, 21%;P=0.032). Point mutations in K-ras were identified by dot blot hybridization analysis of PCR-amplified fragments with mutation-specific oligonucleotides and by direct sequencing. The overall frequency of K-ras mutations was 19/70 (27%).K-ras mutations were found in 12 of 17 (71%) mucinous tumors (8/12 mucinous carcinomas [67%] and 4/5 mucinous tumors of borderline malignancy [80%]), and occurred more frequently than in serous carcinomas (4/31, 13%;P=0.00009) or in all nonmucinous types of ovarian epithelial tumors combined (7/53, 13%; p=0.00002). These data suggest that different combinations of oncogenes and/or tumor suppressor genes may be involved in the genesis and development of histologically distinct categories of common epithelial tumors of the human ovary.     

间皮素mRNA及蛋白在卵巢癌中的表达及分析

目的 研究间皮素(MESO)在卵巢癌中的表达及意义.方法 用逆转录聚合酶链反应(RT-PCR)技术和免疫组化方法分别检测卵巢肿瘤和正常卵巢组织中MESO mRNA及其蛋白水平.结果MESO mRNA和蛋白在上皮性卵巢癌(1.4005 ±0.4646,2.7857±2.2712)和交界性卵巢肿瘤(1.0650 ±0.3100,2.9167 ±2.391)中的表达水平高于良性卵巢肿瘤(0.6463±0.2419,1.2500 ±1.6125)和正常卵巢组织(0.6439 ±0.2729,0.9167 ±1.2401),差异有统计学意义(P＜0.05);MESOmRNA和蛋白在浆液性卵巢癌(1.5255 ±0.4151,3.3036 ±2.6141)和子宫内膜样癌(1.5250 ±0.5419,3.0000 ±2.3094)中的表达水平高于黏液样癌(1.0675±0.3149,1.0556 ±1.9242),差异有统计学意义(P＜0.05);临床Ⅲ、Ⅳ期MESO表达水平(1.5100 ±0.4142,3.6087 ±3.3959)高于Ⅰ、Ⅱ期(1.1190 ±0.4909,1.7895 ±2.6320),差异有统计学意义(P＜0.05).MESO表达水平与病理分级有关(P＜0.05),而与患者年龄和血清CA125水平无关(P＞0.05).结论 MESO mRNA及蛋白在卵巢癌和交界性肿瘤组表达增高,MESO可能参与卵巢癌的黏附转移.     

卵巢癌中EIF-5A2 基因表达与临床意义*

目的:探讨真核翻译起始因子5A2（EIF-5A2）基因在卵巢上皮性肿瘤中的表达及其临床意义。方法:运用免疫组化和荧光原位杂交方法,结合组织芯片技术,检测EIF-5A2 基因在50例卵巢腺瘤、50例卵巢交界性肿瘤和150 例卵巢癌中的表达,分析其与肿瘤临床病理学参数之间的相关性。结果:免疫组化检测结果,分别有6.4% 的卵巢良性腺瘤、28.3% 的交界性肿瘤和56.6% 的卵巢癌出现EIF-5A2 蛋白的过度表达。在卵巢癌中,EIF-5A2 蛋白表达与肿瘤的组织学Silverberg 氏分级和临床FIGO分期均有显著的相关性（P<0.05）,其中70.0% 的高级别（G3 级）的卵巢癌出现EIF-5A2 蛋白的过度表达,明显高于G1/G2 级的卵巢癌（49.5%）;在FIGO分期中,65.6% 的临床晚期（Ⅲ/Ⅳ期）卵巢癌呈EIF-5A2 蛋白过度表达,明显高于Ⅰ/Ⅱ期的肿瘤（38.3%）。 另外,EIF-5A2 蛋白过度表达与卵巢癌细胞增殖（Ki-67的表达水平）显著正相关（P<0.01）,大多数（72.8%）EIF-5A2 蛋白过度表达的卵巢癌中出现Ki-67蛋白高表达,而多数（66.1%）EIF-5A2 蛋白正常表达的卵巢癌则呈Ki-67蛋白低表达。荧光原位杂交结果显示,只有13.8% 的卵巢癌出现EIF-5A2 基因扩增;卵巢交界性肿瘤和良性腺瘤中均未观察到EIF-5A2 基因的扩增。结论:EIF-5A2 蛋白过度表达可能通过促进肿瘤细胞增殖的效应,在卵巢上皮性肿瘤的发生发展中起重要作用,而且与卵巢癌的恶性组织学表型和浸润转移密切相关。      

Second primary or recurrence? Comparative patterns of p53 and K-ras mutations suggest that serous borderline ovarian tumors and subsequent serous carcinomas are unrelated tumors

The role of serous borderline ovarian tumors (BOTs) in the pathogenesis of serous ovarian carcinomas is unclear. Some authors have compared mutations in serous BOTs to those in serous ovarian carcinomas, but the data on two common oncogenes, p53 and K-ras, remain inconclusive. To further clarify the relationship between the two tumors, we performed mutational analysis on tumors from a set of eight patients who first presented with advanced-stage serous BOTs and later developed grade 1 serous carcinomas. Epithelium from eight advanced-stage serous BOTs and subsequent grade 1 papillary serous carcinomas was microdissected and retrieved using a PixCell laser-capture microscope. Stroma was dissected as an internal control. The DNA was extracted with proteinase K and analyzed by single-strand conformational polymorphism-PCR for p53 and K-ras mutations. Bands with altered motility were analyzed by direct cycle sequencing. Seven of eight patients demonstrated different mutations in the secondary tumor compared with the primary tumor. For three patients, p53 mutations were identified in the BOTs that were absent from the carcinomas, suggesting a nonclonal origin for the carcinomas. These findings are consistent with the hypothesis that advanced-stage serous BOTs represent a distinct pathological entity compared with grade 1 serous epithelial ovarian carcinoma.     

Expression of the MAGE-A4 and NY-ESO-1 cancer-testis antigens in serous ovarian neoplasms.

PURPOSE: The cancer-testis (CT) family of antigens is expressed in a variety of malignant neoplasms and is silent in normal tissues, except for the testis. Expression of two members of this family, MAGE-A4 and NY-ESO-1, has been described in melanomas, germ cell tumors, certain carcinomas and sarcomas, and more recently in uterine neoplasms. The objective of this study was to evaluate the extent and prognostic significance of CT antigen expression in ovarian serous neoplasms. EXPERIMENTAL DESIGN: Seventy-four patients with ovarian neoplasms, including 10 with serous cystadenomas, 11 with serous tumors of borderline malignancy, and 53 with serous carcinomas, were studied. Immunohistochemistry was performed with the 57B monoclonal antibody, which recognizes predominantly the MAGE-A4 antigen and the D8.38 antibody that recognizes NY-ESO-1. RESULTS: MAGE-A4 expression was found to be present in 57% of the serous carcinomas and only in 9% of the serous tumors of borderline malignancy. No staining was detected in serous cystadenomas or in the normal ovary. In 8 of 30 positively stained serous carcinomas, >50% of the tumor cells expressed MAGE-A4. NY-ESO-1 expression was seen in 19% of the serous carcinomas, whereas serous tumors of borderline malignancy and cystadenomas were negative. A significant inverse correlation was found between MAGE-A4 expression and patient survival (P = 0.016). Multivariate analysis revealed that both tumor stage and MAGE-A4 expression were independent predictors of patient survival (P = 0.022 and P = 0.013, respectively). CONCLUSIONS: Cancer-testis antigen expression in ovarian serous neoplasms correlates directly with their degree of malignancy. MAGE-A4 expression, and to a lesser degree NY-ESO-1 expression, is characteristic of the majority of serous carcinomas. Determining the degree of MAGE-A4 expression in these tumors may provide important prognostic information. Finally, MAGE-A4 may represent a novel target for immunotherapy in serous ovarian neoplasms.     

Quantitative analysis of follicle-stimulating hormone receptor in ovarian epithelial tumors: a novel approach to explain the field effect of ovarian cancer development in secondary mullerian systems

The role of FSHR expression in ovarian cancer development is not clear. We examined quantitative expression of FSHR in different types of OET, presumed precursor lesions and peritoneal implants and further discussed FSH as a key growth-promotion factor for the process of ovarian epithelial tumorigenesis. Thirty-five primary OET specimens, including 5 serous cystadenomas, 4 papillary serous cystadenomas, 9 SBTs and 17 serous carcinomas, were examined for quantitative FSHR expression. Ten paired samples (3 benign cystadenomas, 5 SBTs and 2 carcinomas) were obtained from several morphologically different areas, including benign-looking, borderline and cancerous areas in the same OETs, and from the remaining ovarian tissue and contralateral ovaries. Competitive RT-PCR was performed to measure the quantitative expression of FSHR in each tissue sample. FSHR expression levels were compared among nonpaired samples and within paired samples. We found that OSE had the lowest FSHR expression, whereas antral follicles had the highest level. Within benign OETs, papillary serous cystadenomas have 4.9-fold higher FSHR levels than nonpapillary serous cystadenomas. SBTs had the highest level of FSHR expression, which was 12.8-fold, 2.7-fold and 2.4-fold higher than that of serous cystadenomas, papillary serous cystadenomas and grade 1 carcinomas, respectively. A similarly high level of FSHR mRNA was found in peritoneal implants, which were associated with SBTs. FSHR levels among serous carcinomas decreased with an increase in carcinoma grade. Grade 3 carcinomas had the lowest FSHR level, which was similar to that of serous cystadenomas, while grade 1 carcinomas had 6.5-fold higher FSHR levels than those in serous cystadenomas. Our results suggest that not only serum FSH but also FSHR in ovarian epithelium may play important roles in ovarian OET development. Both the receptor and ligand may act in a synergistic way to promote tumor growth. The observation that high FSHR levels are present in peritoneal implants suggests that FSH may also play a similar role in the development of peritoneal serous tumors. From this perspective, circulating FSH may be considered a driving force in the field effect theory for the development of both ovarian neoplasms and their associated peritoneal implants. However, the exact role of FSH and/or FSHR in the development of epithelial tumors arising in both the ovary and peritoneum needs further investigation.     

GLUT-1和DNA-PKcs在卵巢浆液性肿瘤组织中的表达及其意义

背景与目的:已知肿瘤细胞生长所需能量是通过葡萄糖转运体蛋白1(glucose transporter protein 1,GLUT-1)完成的葡萄糖代谢来提供的.另外,参与基因损伤修复的催化亚单位--DNA蛋白激酶(DNA-dependent protein kinase catalytic subunit,DNA-PKcs)在肿瘤形成中也起着非常重要的作用.本研究旨在探讨GLUT-1和DNA-PKcs在卵巢浆液性肿瘤组织中的表达及其与肿瘤生物学行为的关系和意义.方法:免疫组化方法检测80例卵巢浆液性肿瘤组织中GLUT-1、DNA-PKcs的表达,分析其异常表达与临床病理参数之间的相关性.以正常卵巢组织20例为对照.结果:正常卵巢组织GLUT-1表达全阴性,DNA-PKcs表达全阳性.GLUT-1在良性、交界性、恶性卵巢浆液性肿瘤中的表达呈增高的趋势,与卵巢浆液性肿瘤的发生发展呈正相关(rs=0.943,P＜0.01);在恶性肿瘤中的阳性率(100%)明显高于交界性(55%).DNA-PKcs在良性、交界性和恶性卵巢浆液性肿瘤中的阳性率分别为95%、90%、60%,差异有统计学意义(P＜0.01).GLUT-1与DNA-PKcs的表达呈负相关(rs=-0.270,P＜0.01).GLUT-1表达与临床分期、腹腔种植、腹水、淋巴结转移均相关(P＜0.05);DNA-PKcs仅与临床分期和淋巴结转移相关(P＜0.05),与腹水、腹腔种植无关(P＞0.05).结论:GLUT-1的异常表达和DNA-PKcs的丢失与卵巢浆液性肿瘤恶变相关.     

Immunohistochemical Expression of Placental Alkaline Phosphatase and Vimentin in Epithelial Ovarian Neoplasms

The immunohistochemical expression of PLAP and vimentin was assessed in 23 benign, 6 borderline malignant and 31 malignant epithelial ovarian neoplasms. PLAP and vimentin were expressed in some benign (3/23 and 5/23 respectively) and borderline malignant (2/6 for both markers) tumours and they were often expressed in malignant tumours (16/31 and 17/31 respectively). There was a significantly increased expression of PLAP and vimentin in serous cystadenomas and serous carcinomas compared to their mucinous counterparts. Although there was no significant correlation between PLAP expression and histologic grade of carcinomas there was a trend towards increased expression in more differentiated carcinomas. No correlation was found between vimentin expression and degree of differentiation.     

Skp2 overexpression is a prognostic factor in patients with ovarian adenocarcinoma.

PURPOSE: The purpose of this study was to examine Skp2 expression in epithelial ovarian tumors and to identify the association of Skp2 expression levels with patient survival. EXPERIMENTAL DESIGN: Skp2 protein expression was examined by immunohistochemistry in 134 epithelial ovarian tumors [20 adenomas, 23 low malignant potential (LMP) tumors, and 91 adenocarcinomas]. Results of immunostaining were correlated with clinicopathological variables and overall survival. Skp2 mRNA expression was examined by semiquantitative PCR in 32 ovarian adenocarcinomas and in 3 ovarian cancer cell lines. RESULTS: Skp2 expression was detected in neither ovarian adenomas nor LMP tumors. In contrast, Skp2 expression was detected in 47.3% (43 of 91) of adenocarcinomas. Positive Skp2 expression was detected significantly more often in adenocarcinomas than in LMP tumors (P < 0.0001) or in adenomas (P < 0.0001). A significantly higher detection rate of Skp2 expression was observed in advanced-stage diseases compared with early-stage diseases (P = 0.010). Log-rank testing showed that Skp2 overexpression was significantly correlated with poor patient survival (P = 0.0035). Older age (P = 0.0026), advanced clinical stage (P < 0.0001), and high histological grades of the tumors (P = 0.0018) were also significantly associated with poor prognoses. In multivariate analysis, Skp2 overexpression (P = 0.0069) and clinical stage (P < 0.0001) remained significantly associated with overall survival, whereas age and histological grade lost their significance. Considerable levels of Skp2 mRNA expression were detected in all ovarian adenocarcinomas examined by semiquantitative PCR. CONCLUSIONS: Skp2 expression might play an important role in the development and progression of ovarian adenocarcinomas, and Skp2 overexpression is an independent prognostic marker of ovarian adenocarcinoma patients.