Clinicopathological study of metallothionein immunohistochemical expression, in benign, borderline and malignant ovarian epithelial tumors

Metallothioneins (MTs) are a family of cystein-rich metal-binding proteins, which are expressed in normal cells during fetal and postnatal life but also in a variety of human neoplasms. MT expression in human tumors has been linked to resistance to anticancer drugs and differentiation and progression in some types of tumors. This study examined the immunohistochemical expression of MTs in benign, borderline and malignant tumors of ovarian surface epithelium and the possible correlations with clinicopathological parameters and survival. A total of 87 cases with diagnosis of ovarian surface epithelial tumors were included. Specifically, 21 cases of benign cystadenomas (11 serous and 10 mucinous), 14 borderline (low malignant potential tumors, 8 mucinous and 6 serous) and 52 cases of ovarian cancer were analysed. Immunohistochemical expression of MT (cut-off level > 10% of tumor cells) was clearly associated with malignancy. A statistically significant correlation was found between the expression of MT in cancer cases and benign tumors (p < 0.0001) and cancer cases and borderline tumors p = 0.003. In cancer cases a difference was observed between grade I and III (p = 0.002). There was no correlation of MT overexpression with survival in the small number of ovarian carcinoma patients where it was analysed. MT constitutes a marker that characterizes aggressiveness and a high malignant potential in ovarian epithelial tumors. In diagnostic problems MT may help distinguish between benign, borderline and malignant tumors.     

Nuclear morphometry and AgNOR quantification: computerized image analysis on ovarian mucinous tumor imprints

OBJECTIVE: To determine the morphometric characteristics of nuclei and silver-stained nucleolar organizer regions (AgNORs) on cytologic imprints and their value in differential cytodiagnosis of benign, atypical proliferative (borderline) and malignant ovarian mucinous tumors. STUDY DESIGN: Forty-six mucinous ovarian tumor imprints (16 benign, 15 borderline, 15 malignant), were analyzed. Nuclear area, outline, "shape factor" and "form factor" were measured on Papanicolaou-stained smears. AgNOR quantification included 7 variables related to the number and area of single, cluster, total and relative AgNOR content per nucleus and the size distribution of AgNORs. RESULTS: Nuclear area and shape factor allowed distinguishing borderline and malignant tumors. The nuclear area in benign tumors was larger than that in borderline tumors; malignant tumors had the highest values. Single and cluster AgNORs were statistically significantly different in borderline tumors compared with malignant tumors, except for the cluster AgNOR area. The total AgNOR area, number and relative area increased from benign through malignant tumors, with statistically significant differences among all groups. By AgNOR size distribution, small AgNORs discriminate malignant from borderline and benign tumors. CONCLUSION: Combining nuclear morphometry and AgNOR analysis on cytologic imprints could be a diagnostically useful method in the assessment of mucinous ovarian tumors.     

卵巢上皮肿瘤淋巴转移与血管内皮生长因子C的表达

The aim of the present study was to explore the role of vascular endothelial growth factor-C (VEGF-C) in the process of angiogenesis, lymphangiogenesis and lymphatic metastasis in epithelial ovarian tumors. In situ hybridization and immunohistochemical staining for VEGF-C were performed in 30 epithelial ovarian carcinomas, 9 borderline tumors and 26 benign cystadenomas. Endothelial cells were immunostained with anti-VEGFR-3 pAb and anti-CD31 mAb, and VEGFR-3 positive vessels and microvessel density (MVD) were assessed by image analysis. VEGF-C mRNA and protein expression in ovarian epithelial carcinomas were significantly higher than that in borderline tumors and benign cystadenomas (p < 0.05 or p < 0.01). In ovarian epithelial carcinomas, VEGF-C protein expression, VEGFR-3 positive vessels and MVD were significantly higher in the cases of clinical stage III-IV and with lymphatic metastasis than those of clinical stage I-II and without lymphatic metastasis respectively (p < 0.05 or p < 0.01), VEGFR-3 positive vessels and MVD was significantly higher in the VEGF-C protein positive tumors than negative tumors (p < 0.05), VEGFR-3 positive vessels was significantly correlated with MVD(p < 0.01). These data suggest that VEGF-C might play a role in lymphatic metastasis via lymphangiogenesis and angiogenesis in epithelial ovarian carcinomas, and VEGF-C could be used as a biologic marker of metastasis in ovarian epithelial carcinomas.     

Alpha(v)beta(6) integrin-A marker for the malignant potential of epithelial ovarian cancer.

The mechanism(s) responsible for the progression of non-metastatic or borderline ovarian cancer to invasive Grade I/III ovarian cancer is still unknown. An epithelium-restricted integrin, alpha(v)beta(6), is present in malignant epithelia but not in normal epithelia. We studied the relative expression and distribution of alpha(v)beta(6) integrin in early and late-stage invasive (Grade I and Grade III) and non-invasive (benign and borderline) ovarian tumors of serous, mucinous, endometrioid, and clear-cell carcinoma subtypes, to assess its potential as a marker for epithelial ovarian cancer progression. Sixty-six specimens, including eight normal, 13 benign, 14 borderline, 13 Grade I, and 18 Grade III tumors were evaluated by immunohistochemistry (IHC) using a monoclonal antibody (MAb) against alpha(v)beta(6) integrin. Normal ovarian surface epithelium was negative for alpha(v)beta(6) integrin expression. All 45 carcinomas studied were positive, and the staining intensity significantly correlated with the grade of the tumor. The Grade III carcinomas of all types showed strong staining intensity. Only mucinous benign tissues were positive, and no reactivity was observed in benign serous neoplasms. On the basis of these observations, we hypothesize that the expression of alpha(v)beta(6) integrin is associated with epithelial ovarian cancer and that a gradual increase in the expression of the molecule may be a correlative index of the progression of this disease.     

Diagnostic utility of GLUT-1 expression in the cytologic evaluation of serous fluids

OBJECTIVE: To evaluate the extent to which adenocarcinomas in body cavity fluids express GLUT-1 in comparison to currently available markers for adenocarcinomas. STUDY DESIGN: Archival paraffin-embedded cell blocks of serous fluids from 25 cases of benign effusions containing reactive mesothelial cells and 39 cases of malignant effusions with metastatic adenocarcinoma (11 ovarian, 11 pulmonary, 9 gastrointestinal and 8 breast) were retrieved from the surgical pathology files. All cases were stained with antibodies for GLUT-1, Ber-Ep4, B72.3 and CEA. Positive staining was defined as distinct linear membrane staining for GLUT-1 and Ber-EP4, cytoplasmic staining for CEA, and cytoplasmic or membrane staining for B72.3. Strong staining in at least 10% of the tumor cells was required in order to consider the case positive for the particular marker. RESULTS: GLUT-1 was expressed in 72% (28 of 39) of cases of malignant effusions: 100% (11 of 11) from the ovary, 91% (10 of 11) from the lung, 67% (6 of 9) from the gastrointestinal tract and 12% (1 of 8) from the breast. None (0 of 25) of the benign effusions expressed GLUT-1. Malignant effusions expressed CEA in 74% (29 of 39), Ber-Ep4 in 85% (33 of 39), and B72.3 in 62% (24 of 39). Benign effusions expressed CEA in 3 cases and B72.3 in 2 cases. CONCLUSION: GLUT-1 is a useful marker that can be applied to cytologic specimens. It can be used as a reliable component of an antibody panel to distinguish reactive mesothelial cells from metastatic adenocarcinoma in particular adenocarcinomas of body cavity effusions, in particular adenocarcinomas of ovarian and pulmonary origin.     

Expression of Serum Amyloid A in Human Ovarian Epithelial Tumors: Implication for a Role in Ovarian Tumorigenesis

Serum amyloid A (SAA) is an acute phase protein which is expressed primarily in the liver as a part of the systemic response to various injuries and inflammatory stimuli; its expression in ovarian tumors has not been described. Here, we investigated the expression of SAA in human benign and malignant ovarian epithelial tumors. Non-radioactive in situ hybridization applied on ovarian paraffin tissue sections revealed mostly negative SAA mRNA expression in normal surface epithelium. Expression was increased gradually as epithelial cells progressed through benign and borderline adenomas to primary and metastatic adenocarcinomas. Similar expression pattern of the SAA protein was observed by immunohistochemical staining. RT-PCR analysis confirmed the overexpression of the SAA1 and SAA4 genes in ovarian carcinomas compared with normal ovarian tissues. In addition, strong expression of SAA mRNA and protein was found in the ovarian carcinoma cell line OVCAR-3. Finally, patients with ovarian carcinoma had high SAA serum levels, which strongly correlated with high levels of CA-125 and C-reactive protein. Enhanced expression of SAA in ovarian carcinomas may play a role in ovarian tumorigenesis and may have therapeutic application. (J Histochem Cytochem 58:1015–1023, 2010)     

Expression of PTEN in ovarian epithelial tumors and its relation to tumor behavior and growth

OBJECTIVE: To evaluate the expression of tumor suppressor gene phosphatase and tensin homologue on chromosome 10 (PTEN) in ovarian epithelial tumors and its correlation with tumor growth and clinicopathologic features in ovarian adenocarcinomas. STUDY DESIGN: Immunohistochemical staining with anti-PTEN antibody was performed in 54 adenocarcinomas and 23 borderline tumors of the ovary. The apoptotic cells were visualized by terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling, and proliferative cells were visualized by staining with Ki-67 antibody. RESULTS: Reduced PTEN expression was significantly higher among the adenocarcinomas than the borderline tumors (p < 0.001). Reduced PTEN expression in adenocarcinomas did not correlate with International Federation of Obstetrics and Gynecology (FIGO) stage. The Ki-67 index (KI) and apoptotic index were significantly higher in adenocarcinomas as compared with borderline tumors (p < 0.001). Tumors with reduced PTEN expression in ovarian adenocarcinomas had a significantly higher KI than those with normal PTEN expression (p < 0.01). By univariate analysis, FIGO stage and histologic type correlated with survival. However, FIGO stage was the only independent prognostic factor by multivariate analysis. CONCLUSION: Our results suggest that alteration of the PTEN gene may be associated with malignant transformation of ovarian epithelial tumors. The PTEN gene seems to be a negative regulator of cell proliferation in ovarian adenocarcinomas.     

Decreased expression of autophagy-related proteins in malignant epithelial ovarian cancer

Some studies have shown that the change of autophagic capacity may correlate with malignant transformation. Our study was designed to investigate the expression and significance of two autophagy-related proteins, microtubule-associated protein 1 light chain 3 (LC3) and Beclin 1 in the tumorigenesis and development of epithelial ovarian carcinoma. We observed that the positive expression of LC3 and Beclin 1 was significantly higher in the samples of benign and borderline ovarian tumors than those in malignant epithelial ovarian cancers. The expression of LC3 and Beclin 1 was associated with FIGO stage and histological grade. No significant relationship was observed between age and histological grade. However, we observed that the expression of LC3 was not related to Beclin 1. Therefore, the decrease of autophagic capacity may be related to tumorigenesis and development of epithelial ovarian cancer.     

Copper content in ascitic fluid is associated with angiogenesis and progression in ovarian cancer

BackgroundAscites is associated with the poor prognosis of malignant tumors. The biological importance of the changes in the content of trace elements in the ascitic fluid is unknown. Herein, we analyzed trace elements in the ascitic fluid of patients with ovarian tumors and used cultured cells to determine the copper (Cu)-induced changes in gene expression in ovarian cancer.MethodsInductively coupled plasma mass spectrometry (ICP-MS) was used to compare ascitic fluid trace element levels in patients with benign ovarian tumors (n = 22) and borderline/malignant tumors (n = 5) for primary screening. Cu levels were validated using atomic absorption spectrometry (AAS) in 88 benign, 11 borderline, and 25 malignant ovarian tumor patients. To confirm Cu-induced gene expression changes, microarray analysis was performed for Cu-treated OVCAR3, A2780, and Met5A cells. The vascular endothelial growth factor (VEGF) concentration in the cell supernatant or ascitic fluid (ovarian cancer samples) was measured using ELISA.ResultsICP-MS showed that Co, Ni, Cu, Zn, As, Se, and Mo levels significantly increased in patients with malignant/borderline ovarian tumors compared to those in patients with benign ovarian tumors. AAS showed that malignant ovarian tumors were independently associated with elevated levels of Cu in ascites adjusted for age, body mass index, alcohol, smoking, and supplement use (p < 0.001). Microarray analysis of both Cu-treated ovarian cancer cell lines OVCAR3 and A2780 and the mesothelial cell line Met-5A revealed the upregulation of the angiogenesis biological process. Real-time polymerase chain reaction and ELISA demonstrated that an increased Cu content significantly enhanced VEGF mRNA expression and protein secretion in OVCAR3, A2780, and Met-5A cells. VEGF levels and clinical stages of the tumors correlated with the ascitic fluid Cu content in patients with malignant ovarian tumors (correlation coefficient 0.445, 95 % confidence interval [CI]: 0.069–0.710, p = 0.023 and correlation coefficient 0.406, 95 % CI: 0.022–0.686, p = 0.040, respectively).ConclusionCu levels significantly increased in patients with malignant ovarian cancer. Cu induced angiogenic effects in ovarian cancer and mesothelial cells, which affected ascites fluid production. This study clarifies the link between elevated Cu in ascites and malignant ovarian tumor progression. Strategies to decrease Cu levels in the ascitic fluid may help downregulate VEGF expression, thereby improving the prognosis of ovarian malignancies.     

Protein expression changes in ovarian cancer during the transition from benign to malignant

Epithelial ovarian carcinoma has in general a poor prognosis since the vast majority of tumors are genomically unstable and clinically highly aggressive. This results in rapid progression of malignancy potential while still asymptomatic and thus in late diagnosis. It is therefore of critical importance to develop methods to diagnose epithelial ovarian carcinoma at its earliest developmental stage, that is, to differentiate between benign tissue and its early malignant transformed counterparts. Here we present a shotgun quantitative proteomic screen of benign and malignant epithelial ovarian tumors using iTRAQ technology with LC-MALDI-TOF/TOF and LC-ESI-QTOF MS/MS. Pathway analysis of the shotgun data pointed to the PI3K/Akt signaling pathway as a significant discriminatory pathway. Selected candidate proteins from the shotgun screen were further confirmed in 51 individual tissue samples of normal, benign, borderline or malignant origin using LC-MRM analysis. The MRM profile demonstrated significant differences between the four groups separating the normal tissue samples from all tumor groups as well as perfectly separating the benign and malignant tumors with a ROC-area of 1. This work demonstrates the utility of using a shotgun approach to filter out a signature of a few proteins only that discriminates between the different sample groups.     

Decreased expression of autophagy-related proteins in malignant epithelial ovarian cancer

Some studies have shown that the change of autophagic capacity may correlate with malignant transformation. Our study was designed to investigate the expression and significance of two autophagy-related proteins, microtubule-associated protein 1 light chain 3 (LC3) and Beclin 1 in the tumorigenesis and development of epithelial ovarian carcinoma. We observed that the positive expression of LC3 and Beclin 1 was significantly higher in the samples of benign and borderline ovarian tumors than those in malignant epithelial ovarian cancers. The expression of LC3 and Beclin 1 was associated with FIGO stage and histological grade. No significant relationship was observed between age and histological grade. However, we observed that the expression of LC3 was not related to Beclin 1. Therefore, the decrease of autophagic capacity may be related to tumorigenesis and development of epithelial ovarian cancer.

Addendum: Shen Y, Liang LZ, Hong MH, Xiong Y, Wei M, Zhu XF. Expression and clinical significance of microtubule-associated protein 1 light chain 3 (LC3) and Beclin1 in epithelial ovarian cancer. Ai Zheng 2008; 27:595-9.     

中国人卵巢上皮性肿瘤nm23H1基因遗传不稳定性的研究

The aim of this study was to examine microsatellite instability (MSI) and loss of heterozygosity (LOH) of locus D17S396 on chromosome 17 and their influence on the expression of nm23H1 in the epithelial ovarian tumors, which may provide experimental basis for the mechanism of nm23H1 gene and tumor metastasis. Techniques such as DNA extraction from formalin-fixed paraffin-embedded tissues, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), ordinary silver stain were used to study MSI and LOH of locus D17S396. Envision immunohistochemistry and Leica-Qwin computer imaging techniques were used to assess the expression of nm23H1 gene. In our experiments, the frequency of heredity instability of malignant ovarian tumors was 40%, which is higher than that of borderline ovarian tumors, while there were no heredity instability occurred in benign ovarian tumors and normal ovarian tissue. Among 25 epithelial ovarian carcinomas, the frequency of LOH in lymph node metastasis cases (66.67%) was significantly higher than those without metastasis (10.53%). Moreover, the frequency of LOH was higher in FIGO stage III and IV than in stage I and II. However, the frequency of MSI showed no correlation with any clinicopathologic characteristics. The positive frequency of nm23H1 protein in the ovarian epithelial carcinoma and borderline tumors were 56.00% and 57.14%, respectively. They were both higher than those of the benign tumors and normal ovarian tissue. In the epithelial ovarian carcinomas, the positive frequency of nm23H1 protein in lymph node metastasis case was significantly lower than those without metastasis. FIGO stage III and IV also exhibited lower positive frequency of nm23H1 protein compared with stage I and II. Furthermore, there was no difference in nm23H1 protein expression intensity analyzed by computer imaging. In the epithelial ovarian carcinomas, the positive frequency of nm23H1 protein in LOH positive group was 0.00%, which is lower than that of LOH negative group (P < 0.01). The results indicated that the heredity instability of nm23H1 gene might be implicated in pathogenesis and progression of epithelial ovarian tumor. The occurrence of LOH might be the molecule marker of the deteriorism of ovarian tissue. Both MSI and LOH of nm23H1 gene controlled development of the epithelial ovarian tumor independently in different paths. LOH could inhibit the expression of nm23H1 in local tissue of the epithelial ovarian carcinoma, which endowed it with high aggressive and poor prognosis. Increasing the amount of nm23H1 protein expression could effectively restrain metastasis of the ovarian epithelial carcinoma and improve prognosis of patients.     

HE4、NF-κBp65和MMP-9在卵巢上皮性肿瘤中的表达及其临床意义

目的探讨HE4、NF-κBp65以及MMP-9的表达与上皮性卵巢肿瘤临床病理生物学行为的关系以及对患者预后的影响。方法应用免疫组化对80例卵巢上皮性癌、10例交界性上皮性肿瘤及10例良性上皮性肿瘤组织进行HE4、NF-κB p65及MMP-9蛋白的检测。结果 HE4、NF-κBp65及MMP-9蛋白的阳性表达率在卵巢癌组均高于交界性及良性肿瘤组（P〈0.05）。三个指标的表达与EOC的组织学分级、腹腔脏器及淋巴结转移以及PTNM临床分期有关（P〈0.05）;在EOC中,NF-κBp65分别与HE4、MMP-9的表达呈正相关（r1=0.673,P〈0.05;r2=0.775,P〈0.05）。多因素分析,PTNM分期、MMP-9的表达是影响卵巢癌术后患者预后的独立因素（P〈0.05）;HE4阳性组与阴性组5年生存率分别为12.7%和84.0%,MMP-9阳性组与阴性组5年生存率分别为8.7%和70.6%,差异均有统计学意义（P〈0.05）。结论 NF-κBp65可能通过上调HE4、MMP-9的表达促进EOC的浸润和转移,联合检测HE4、NF-κBp65以及MMP-9的表达可能作为预测和评价患者预后的生物学指标。     

联合检测E-cadherin, VEGF表达水平在卵巢良恶性肿瘤诊断中的临床价值

目的:探讨联合检测E-钙粘素(E-cadherin)、血管内皮生长因子(VEGF)表达水平在卵巢良恶性肿瘤诊断中的临床价值。方法:收取2012年1月至2016年1月间我院收治的卵巢良恶性肿瘤患者共83例,使用免疫组化方法检测对E-cadherin及VEGF表达情况进行分析与比较。结果:E-cadherin在卵巢良性肿瘤、卵巢交界性肿瘤及卵巢恶性肿瘤中的阳性表达率分别为64.71%、44.44%及25.00%,VEGF在卵巢良性肿瘤、卵巢交界性肿瘤及卵巢恶性肿瘤中的阳性表达率分别为11.76%、33.33%及83.33%,上述差异均具有统计学意义(P0.05)。E-cadherin及VEGF在卵巢恶性肿瘤中的表达与分化程度、FIGO分期有关(P0.05)。VEGF表达与淋巴结转移有关(P0.05),但E-cadherin与淋巴结转移关系不大(P0.05)。E-cadherin及VEGF表达呈负相关(r=-0.472,P0.05)。结论:E-cadherin低表达及VEGF高表达与卵巢恶性肿瘤发生、发展及侵袭有密切关系。     

Selenium as a modulator of membrane stability parameters and surface changes during the initiation phase of 1,2-dimethylhydrazine induced colorectal carcinogenesis

Epithelial ovarian cancer (EOC) represents the most challenging of gynecological malignancies. Defective apoptosis is a major causative factor in the development and progression of cancer. The two important pathways of apoptosis are extrinsic death receptor pathway (Fas family) and intrinsic mitochondrial pathway (Bcl-2 family). In this study, differential protein expression of the major Fas family members (Fas, FasL, and FAP-1) and Bcl-2 family members (Bax, Bcl-2, and Bcl-X(L)) in benign versus malignant surface epithelial ovarian tumors was evaluated at the protein level by immunohistochemistry. The expression of these molecules was compared in 30 benign versus 35 malignant surface epithelial ovarian tumors. The findings of the present study showed that there was no significant difference in the expression of the Fas family members in benign and malignant ovarian tumors. However, benign tumors showed higher levels of anti-apoptotic Bcl-2 protein levels (p < 0.009), whereas malignant tumors showed higher levels of pro-apoptotic Bax (p < 0.001). In general, there was no significant difference in Bcl-X(L) protein levels. The observations made in the present study suggest that alterations in expression of the Fas family and the Bcl-2 family members occur and play a key role in the deregulated growth of epithelial ovarian cancer.     

Morphometry and digital AgNOR analysis in cytological imprints of benign, borderline and malignant serous ovarian tumours

AIM: The aim of the study was to determine values of a quantitative morphometry analysis of nuclear characteristics and argyrophilic nucleolar organizer regions (AgNORs) in differential cytodiagnosis of benign, atypically proliferating (borderline) and malignant serous ovarian tumours. METHODS: Cytological imprints of benign (n = 20), borderline (n = 19) and malignant (n = 20) ovarian serous tumours were analysed. A computerized, digital analysis was used to determine morphometric nuclear features, the number and characteristics of single AgNORs, cluster AgNORs, total AgNOR and AgNOR area/nucleus (relative area) ratio. According to their size AgNORs were classified in three categories. A one-way variance analysis and post hoc test (Scheffé) were used for statistical analysis. RESULTS: The morphometric nuclear analysis showed that benign, borderline and malignant serous ovarian tumours are statistically different (P < 0.001) according to the area and outline, the values being highest in malignant tumours and lowest in the borderline group. Digital analysis of AgNORs in benign, borderline and malignant groups showed that the total AgNOR number increases with progression of the lesion (meaning tumour malignancy) significantly (P < 0.001) between benign and malignant as well as between borderline and malignant serous ovarian tumours (P < 0.001). The progression of the lesion malignancy was accompanied by a significant (P < 0.001) progressive increase of the total and relative AgNOR area per nucleus. The AgNOR size increases from benign to malignant tumours and a statistically significant difference (P < 0.001) was observed in all three groups regarding small and large AgNORs. CONCLUSION: Combining different markers of morphometric nuclear characteristics and AgNOR values could improve differential cytodiagnosis of benign, borderline and malignant serous ovarian tumours.     

Nerve growth factor induces the expression of chaperone protein calreticulin in human epithelial ovarian cells

Epithelial ovarian cancer is highly angiogenic and high expression of Nerve Growth Factor (NGF), a proangiogenic protein. Calreticulin is a multifunctional protein with anti-angiogenic properties and its translocation to the tumor cell membrane promotes recognition and engulfment by dendritic cells. The aim of this work was to evaluate calreticulin expression in human normal ovaries, benign and borderline tumors, and epithelial ovarian cancer samples and to evaluate whether NGF regulates calreticulin expression in human ovarian surface epithelium and in epithelial ovarian cancer cell lines. Calreticulin mRNA and protein levels were analyzed using RT-PCR, Western blot and immunohistochemistry in 67 human ovarian samples obtained from our Institution. Calreticulin expression induced by NGF stimulation in cell lines was evaluated using RT-PCR, Western blot and immunocytochemistry. We found a significant increase of calreticulin mRNA levels in epithelial ovarian cancer samples as compared to normal ovaries, benign tumors, and borderline tumors. Calreticulin protein levels, evaluated by Western blot, were also increased in epithelial ovarian cancer with respect to benign and borderline tumors. When HOSE and A2780 cell lines were stimulated with Nerve Growth Factor, we found an increase in calreticulin protein levels compared to controls. This effect was reverted by GW441756, a TRKA specific inhibitor. These results suggest that NGF regulates calreticulin protein levels in epithelial ovarian cells through TRKA receptor activation.     

Localisation and expression of aquaporin subtypes in epithelial ovarian tumours

To characterise AQP subtype localisation and expression in epithelial ovarian tumours, immunohistochemistry was used to assess the localisation and expression of AQP1-9 in 30 benign tumour cases, 30 borderline tumour cases, 50 malignant tumour cases and 20 normal ovarian tissue cases. Multiple AQP subtypes were expressed in epithelial ovarian tumours, with each AQP subtype displaying a different pattern of localisation and expression. AQP1 was mainly expressed in the microvascular endothelium, and AQP 2-9 were mainly expressed in tumour cells. Most AQP subtypes co-localised in the basolateral membranes of the epithelia of benign tumours and plasma membranes of malignant tumour cells. The positive rates for AQP1, 5, 6, 7, 8, and 9 were over 50%, but those for AQP2, 3 and 4 were only 10-40%. The expression of AQP1, 5 and 9 in malignant and borderline tumours was significantly higher than that in benign tumours (P<0.05) and normal ovarian tissue (P<0.05). However, AQP6 expression in ovarian malignant and borderline tumours was significantly lower than that in benign tumours (P<0.01) or normal ovarian tissue (P<0.01). AQP1 expression was increased in cases with ascites volumes greater than 1000 mL (P<0.05), AQP5 expression was greater in cases with lymph node metastasis (P<0.05), and more AQP9 expression was observed in G3 cases versus G1 and G2 cases (P<0.01). These results suggest that changes in the distribution and expression of AQP subtypes may be involved in ovarian carcinogenesis. This study presents a novel avenue of research that could illuminate the mechanism of ovarian carcinogenesis and treatment.     

上皮性卵巢癌患者组织P53、Ki67表达及其临床意义

摘要 目的：探讨上皮性卵巢癌患者组织P53、Ki67表达及其临床意义。方法：选择卵巢肿瘤102例,其中病理诊断为良性卵巢肿瘤40例(良性组)和上皮性卵巢癌62例(恶性组),采用免疫组化法检测组织P53、Ki67表达水平,调查患者的临床病理特征并进行相关性分析。结果：恶性组的P53、Ki67表达阳性率为80.6 %和72.6 %,显著高于良性组的10.0 %和12.5 %(P<0.05)。在恶性组中,不同浸润转移、分化程度、病理分期患者的P53、Ki67表达阳性率对比差异有统计学意义(P<0.05)。直线相关分析显示上皮性卵巢癌患者P53表达阳性率与Ki67表达阳性率呈现显著正相关性(r=0.872,P=0.000)。多因素logistic回归分析显示浸润转移、分化程度、病理分期都为影响P53、Ki67表达阳性率的主要因素(P<0.05)。结论：上皮性卵巢癌患者组织P53、Ki67都呈现高表达状况,与患者的临床病理特征显著相关,两者也可互相影响,共同参与上皮性卵巢癌的发生与发展。