髓系细胞触发受体-1在人卵巢癌组织中的表达及其与淋巴结转移的相关性研究

目的:通过检测髓系细胞触发受体-1(TREM-1)在人卵巢癌组织中的表达及其与淋巴转移的相关性,探讨其参与调控肿瘤相关性炎症的可能机制。方法:选择2010年10至2011年10月南昌大学第一附属医院收治的卵巢癌患者30例与卵巢良性肿瘤患者20例。免疫组织化学法测定TREM-1在卵巢癌和卵巢良性肿瘤组织中的表达;用CD163标记M2型肿瘤相关巨噬细胞(TAMs);用D2-40标记微淋巴管,计算微淋巴管密度(LMVD)。分析TREM-1表达与卵巢癌临床病理资料的相关性。结果:卵巢癌组织中TREM-1蛋白的阳性表达率为100%,强阳性表达率为70%(21/30),阳性率显著高于卵巢良性肿瘤的10.0%(2/20)(χ2=42.19,P=0.000)。卵巢良性肿瘤组织中TREM-1和CD163很少表达。TREM-1定位于TAMs。TREM-1表达强度与淋巴转移存在相关性(P=0.01)。Logistic回归分析示,TREM-1评分是淋巴结转移的危险因素(P=0.009)。结论:TREM-1表达于卵巢癌组织的TAMs,其调控的炎症可能在促进卵巢癌淋巴转移中起着重要作用。     

肿瘤浸润淋巴细胞在浆液性卵巢癌的临床病理分析

目的:探讨浆液性卵巢癌中肿瘤浸润性淋巴细胞(TIL)的临床病理和免疫组织化学特征及临床意义。方法:利用免疫组织化学法对68例浆液性卵巢癌中TIL进行组织病理学观察,并分析其与各临床病理因素的关系。结果:68例浆液性卵巢癌中有大量TIL浸润者(≥50 TIL/100肿瘤细胞)43例,占63.24%。有无大量TIL浸润在不同肿瘤细胞分化程度、临床分期、CA125水平中差异有统计学意义(P0.05)。浆液性卵巢癌组织癌巢内CD3~+、CD4~+、CD8~+细胞数显著低于间质内(P0.05);癌巢内CD4~+/CD8~+比值也明显低于间质内(P0.05)。Ⅲ期、低分化组癌巢内及间质内CD4+/CD8~+比值分别低于Ⅰ~Ⅱ期与高-中分化组(P0.05)。癌巢内CD8+/FoxP3~+Treg比值显著低于间质(P0.05);Ⅲ期、低分化组肿瘤癌巢内的CD8+/FoxP3+Treg比值显著降低(P0.05)。Ⅲ期、低分化组患者癌巢中GzmB表达分别低于Ⅰ~Ⅱ期和高-中分化组(P0.05)。结论:有无大量TIL浸润与浆液性卵巢癌肿瘤分化程度、临床分期、CA_(125)水平有关。     

卵巢癌相关成纤维细胞与卵巢癌淋巴结转移的关系

目的:探讨肿瘤相关成纤维细胞(CAFs)与卵巢癌临床病理学特征特别是淋巴结转移的关系,研究CAFs在卵巢癌淋巴管生成和淋巴管内皮细胞(LEC)增殖迁移中的作用。方法:免疫组化法检测、计算机图像处理软件分析71例卵巢癌组织间质中α-平滑肌肌动蛋白(α-SMA)阳性面积百分比,以此代表卵巢癌CAFs的数量。用D2-40标记淋巴管内皮细胞,检测淋巴管密度(LVD)。EdU标记法和Transwell迁移实验检测与CAFs共培养前后淋巴管内皮细胞增殖和迁移情况。结果:卵巢癌有淋巴结转移组间质中CAFs百分比明显高于无淋巴结转移组(P=0.024),分别为(29.39±4.32)%和(22.56±6.78)%。卵巢癌间质CAFs数量与淋巴管密度呈正相关(r=0.504,P=0.0003)。与卵巢癌成纤维细胞共培养后,淋巴管内皮细胞增殖增多2.8倍(P<0.0001),迁移增多5.2倍(P<0.0001)。结论:卵巢癌间质成纤维细胞可能通过促进淋巴管内皮细胞增殖、迁移和淋巴管生成,参与卵巢癌的进展和淋巴结的转移。     

卵巢癌组织中肿瘤浸润淋巴细胞分布特征的研究

目的探讨卵巢癌组织中肿瘤浸润淋巴细胞(TIL)的分布及临床意义。方法1999年1月至2000年12月浙江大学医学院附属妇产科医院应用免疫组化方法检测卵巢癌、良性卵巢上皮性肿瘤和正常卵巢组织中的CD4 、CD8 细胞数,及它们与临床、病理特征的相关性。结果卵巢癌组织中CD4 、CD8 中位数分别为10.6/HPF和25.4/HPF,与良性和正常对照组相比差异有显著性意义。卵巢癌组织癌巢内CD4 、CD8 细胞数显著低于间质内;癌巢内CD4 /CD8 值也明显低于间质内。不同组织类型之间癌巢内CD4 、CD8 和间质内CD8 细胞差异存在显著性意义。Ⅲ期患者癌巢内CD8 和间质内CD4 细胞显著高于Ⅰ～Ⅱ期,而癌巢内的CD4 /CD8 比值显著低于Ⅰ～Ⅱ期;血清CA125≥60kU/L患者间质内CD4 、癌巢内CD8 细胞显著高于<60kU/L者;腹水量≥350mL患者癌巢内CD8 细胞均显著高于腹水量<350mL者;低分化患者间质内CD8 细胞显著高于高分化者,而癌巢内的CD4 /CD8 比值显著低于高分化者。结论卵巢癌组织中TIL数量增加,但主要分布于间质内,且与细胞分化、临床分期等参数有关。     

TAMs与CAFs联合预测子宫颈癌淋巴结转移研究

目的 探讨肿瘤相关巨噬细胞(TAMs)与肿瘤相关成纤维细胞(CAFs)在子宫颈癌组织中的表达分布及其与临床病理参数的相关性,以及二者联合分析对子宫颈癌淋巴结转移的预测意义.方法 从广州医科大学附属第一医院病理科组织样本库中收集55例子宫颈癌组织临床样本,利用免疫组织化学法检测子宫颈癌组织病理切片中CD163+ TAMs...     

巨噬细胞对卵巢癌细胞SKOV3生物学功能的影响

目的:研究巨噬细胞对卵巢癌细胞株SKOV3生物学功能的影响。方法:(1)体外采用IL-4和佛波醇酯(PMA)分别诱导M2和M1型巨噬细胞,流式细胞仪鉴定分型;(2)Tranwell小室建立巨噬细胞与卵巢癌细胞SKOV3体外非接触式共培养模型。比较共培养后,SKOV3的增殖和凋亡、迁移和侵袭的变化。MTT法检测增殖;流式细胞仪Annexin V-FITC/PI双染检测凋亡;Transwell检测侵袭和迁移。结果:(1)IL-4诱导的巨噬细胞高表达CD163,为M2型,PMA诱导组高表达HLA-DR,为M1型。SKOV3和普通巨噬细胞共培养后,巨噬细胞CD163高表达。(2)SKOV3的增殖和凋亡:M2共培养组SK-OV3的增殖活性显著高于M1共培养组和普通共培养组(P<0.05)。M2共培养组SKOV3的凋亡率显著低于M1共培养组和普通共培养组(P<0.05)。(3)SKOV3的迁移和侵袭:M2共培养组SKOV3的侵袭能力显著强于M1共培养组和普通共培养组(P<0.01)。M2共培养组SKOV3的迁移能力显著强于M1共培养组和普通共培养组(P<0.05)。结论:共培养卵巢癌细胞使巨噬细胞M2表型极化。M2型巨噬细胞促进卵巢癌细胞增殖,提高侵袭、迁移能力,减少凋亡,而M1型起相反作用。     

宫颈癌VEGF-C表达和淋巴管、血管生成关系的探讨

目的:检测宫颈癌组织中血管内皮生长因子-C(VEGF-C)、受体VEGFR-3和CD34的表达,探讨VEGF-C与癌周淋巴管、血管生成和肿瘤转移的关系。方法:采用免疫组化法检测55例宫颈癌组织中VEGF-C、VEGFR-3和CD34的表达。结果:55例宫颈癌组织VEGF-C阳性率为69.1%(38/55),VEGFR-3阳性率为61.8%(34/55),二者表达高度一致(P<0.01)。淋巴结转移组中VEGF-C与VEGFR-3阳性表达明显高于无转移组(P<0.05)。低分化组VEGF-C和VEGFR-3的表达明显高于高、中分化组(P<0.05)。随着临床分期增加,VEGFR-3表达的阳性率增高(P<0.01)。淋巴结转移组中淋巴管密度(LMVD)明显高于无转移组(P<0.01)。VEGF-C表达阳性的组织中血管密度(MVD)明显升高(P<0.05)。VEGF-C和VEGFR-3表达阳性的患者生存率有降低的趋势。结论:宫颈癌中VEGF-C通过受体VEGFR-3促进组织生长、抑制分化,促进肿瘤细胞间质淋巴管和血管生成,是促使宫颈癌发生扩散和转移的重要原因。二者阳性表达可预示预后不良。     

靶向肿瘤相关巨噬细胞治疗卵巢癌的研究进展

卵巢癌是致死率最高的妇科恶性肿瘤,免疫因素在卵巢癌的发生、发展中起重要作用。肿瘤相关巨噬细胞（tumor-associated macrophages,TAMs）是卵巢癌肿瘤微环境中重要的免疫细胞,可分泌多种细胞因子促进癌细胞增殖及血管生成并抑制肿瘤免疫,在卵巢癌进展中发挥重要作用。因此,靶向TAMs治疗卵巢癌成为目前的研究热点之一。其具体治疗策略包括：抑制TAMs的募集、增强TAMs的吞噬能力、消耗TAMs、将M2型TAMs去极化为M1型TAMs或抑制TAMs向M2型极化以及阻断TAMs与肿瘤细胞的相互作用。目前,已有诸多基础研究证实化疗药物、免疫检查点阻断剂、纳米药物和中药调节TAMs治疗或协同治疗对卵巢癌具有一定疗效。综述靶向TAMs治疗卵巢癌的原理及相关进展,以期为其进一步研究及临床应用提供参考。     

卵巢上皮癌细胞SKOV3通过分泌外泌体促进单核巨噬细胞分化为肿瘤相关巨噬细胞的研究

目的:研究上皮性卵巢癌细胞SKOV3分泌的外泌体(exosomes)能否调控单核巨噬细胞分化为M2型肿瘤相关巨噬细胞(TAMs),并进一步参与肿瘤的转移。方法:分离SKOV3细胞外泌体,透射电镜观察形态。卵巢癌细胞外泌体、M-CSF+IL-4和空培养基分别与人外周血CD14+单核细胞共培养3天,观察细胞形态。结晶紫计数单核细胞贴壁率;流式细胞仪检测共培养后单核细胞CD206、HLA-DR的表达情况;ELISA法检测共培养后上清中IL-10和IL-12的含量;体外迁移实验检测肿瘤细胞迁移能力的变化。结果:透射电镜显示,外泌体近似圆形,直径30~80nm。结晶紫计数显示,外泌体共培养组和M-CSF+IL-4组的OD值(分别为0.13±0.06,0.16±0.04)较空培养基组(0.04±0.01)增加,差异有统计学意义(P0.05)。倒置显微镜发现,细胞贴壁,形态类似巨噬细胞。流式结果显示,外泌体共培养组和M-CSF+IL-4组的单核细胞CD206(分别为71.86±5.62、99.27±0.32)表达水平升高,HLA-DR(分别为12.71±7.22、3.55±0.27)表达水平降低,与空培养基组比较,差异均有统计学意义(P0.05)。ELISA检测结果显示,外泌体共培养组和M-CSF+IL-4组的上清IL-10含量(分别为71.72±0.81、82.13±2.11)增加,IL-12含量(分别为34.88±4.75、19.71±4.28)减少,与空培养基组比较,差异有统计学意义(P0.05)。体外迁移实验显示,外泌体刺激单核细胞上清组的肿瘤细胞迁移数(121.58±2.25)明显增加,分别与空培养基对照组、单核细胞上清组比较,差异有统计学意义(P0.05)。结论:卵巢上皮癌细胞SKOV3的外泌体可诱导单核巨噬细胞分化极化为卵巢癌腹膜内TAMs表型,从而促进卵巢癌细胞的迁移能力。     

卵巢癌微环境及长链非编码RNA调节巨噬细胞极化的研究进展

肿瘤相关巨噬细胞（TAMs）是肿瘤微环境中最常见的免疫细胞,其在肿瘤组织、远处转移前微环境和转移阳性的淋巴结中均有分布,与肿瘤的进展和预后有关。卵巢癌组织和卵巢癌患者腹水中存在大量的TAMs,然而TAMs浸润、极化和促进肿瘤进展的机制尚不完全清楚。近年长链非编码RNA（lncRNA）在细胞功能调控中的作用逐渐受到重视,其可通过竞争性结合微小RNA（miRNA）、直接与染色质或蛋白质结合而对编码基因进行调控,从而影响细胞的功能。lncRNA与巨噬细胞的极化也有关系,M1型和M2型巨噬细胞的多个lncRNA表达水平具有显著差异。此外,lncRNA也与巨噬细胞的抗原呈递和吞噬功能的调节有关。抑制TAMs的靶向治疗有利于控制卵巢癌的生长和减少腹水量,而以lncRNA为靶点的肿瘤治疗的实验研究也已取得一定的进展。     

Phenotypic characteristics of mononuclear cells in human ovarian tumors — with special reference to cystic and ascitic fluid

The occurrence of mononuclear cells and their cell-surface phenotype was studied in cryo- and paraffin sections in 26 untreated ovarian tumors and in normal ovarian tissue. T cells (positive for CD4 or CD8 markers) were sparsely represented in all sections of normal ovarian tissue and benign ovarian tumors, and in most ovarian cancer sections. B cells were found in three malignant tumors, CD57-positive (natural killer) cells in two, and CD25 (interleukin-2 receptor)-positive cells in one. Macrophages occurred sparsely both in normal ovarian tissue and in benign and malignant ovarian tumors. One endometrioid ovarian cancer, however, manifested rich infiltration of T cells (predominantly positive for CD8 marker). Cystic fluid from malignancies manifested higher prostaglandin concentrations and total cell counts than did benign cystic fluid, but sparse lymphocytes as a rule (5–10% of the total cell count). As compared to cystic fluid, ascitic fluid had higher concentrations both of prostaglandins and cells, with up to 25% lymphocytes in connection with malignancies. Immunogenic activity thus would appear to be weak in ovarian cancer. The harvest of tumor-infiltrating lymphocytes (TIL) from cystic fluid in ovarian cancers is moderate, compared to that of tumor-associated lymphocytes (TAL) from corresponding ascitic fluid samples.     

Expression of aminopeptidase N/CD13 in human ovarian cancers

Aminopeptidase N/CD13 (EC 3.4.11.2) is suggested to play a role in cancer cells invasion, and its activity can be inhibited using specific inhibitors. CD13 inhibitors evoke apoptosis of CD13-positive cancer cells. However, expression of CD13 has not been described in specimens obtained from ovarian carcinomas. Thus, in the present study, the expression of CD13 and its significance was examined in samples of ovarian cancers. The analyses were performed on sections originating from 73 tumor samples (43 from primary laparotomies [PL] and 30 from secondary cytoreductions [SCRs]). Immunohistochemical reactions were performed on paraffin sections of studied tumors, using monoclonal antibodies against CD13. The analysis demonstrated no relationships between the expression of CD13 on one hand and clinical variables and pathologic variables of the patients on the other hand. Expression of CD13 was demonstrated to be significantly more pronounced in samples obtained in PLs as compared to samples from SCRs (P < 0.001). Thus, the data indicate that a potential treatment of ovarian carcinoma with CD13 inhibitors should be performed before chemotherapy or in parallel to first-lapse chemotherapy.     

Expression of chemokine CXCL12 and its receptor CXCR4 in human epithelial ovarian cancer: an independent prognostic factor for tumor progression

OBJECTIVES: Chemokine CXCL12 and its unique receptor CXCR4 have been recently implicated in cancer metastasis. Our goal was to explore expression of CXCL12 and CXCR4 protein in normal ovarian surface epithelium, primary tumors and paired metastases of epithelial ovarian cancer as well as its association with clinicopathological features. We also wanted to test if expression of CXCR4 has prognostic value in epithelial ovarian cancer patients. METHOD: Sections from 6 normal ovarian surface epithelium, 44 primary epithelial ovarian tumors and 30 paired metastatic tumors in omentum were evaluated for CXCL12 and CXCR4 expression using immunohistochemistry (IHC). RESULTS: All samples of normal ovarian surface epithelium were negative for CXCL12 and CXCR4 protein. Ovarian cancer cells mainly showed cytoplasmic staining of CXCL12 and CXCR4. CXCL12 and CXCR4 staining were detected in 40/44 (91%) and 26/44 (59%) patients with primary epithelial ovarian tumors respectively. CXCR4 expression in primary tumors had no significant correlation with lymph nodes metastasis. However, if we combined CXCR4 expression in primary tumors with metastatic tumors, a significant correlation with lymph nodes metastasis was found (P = 0.018). The intensity of CXCL12 staining correlated with ascites (P = 0.014). The rate of CXCR4 expression in refractory and recurrent group (81% versus 28%, P = 0.0008) was significantly higher than that in no-recurrent group. After a median follow-up of 37 months, CXCR4 expression was found associated with an unfavorable prognosis with significantly reduced median disease progression-free survival and overall survival of 15 and 27 months (P = 0.0004, P = 0.017) respectively. Median time-to-event was not reached in patients with negative CXCR4 staining. In multivariate analysis, CXCR4 expression and residual tumor size emerged as independent prognostic factors in epithelial ovarian cancer patients. CONCLUSIONS: This article provides the first evidence that CXCR4 expression could be an independent prognostic factor for epithelial ovarian cancer patients.     

Cytoplasmic CD24 expression in advanced ovarian serous borderline tumors

OBJECTIVES: CD24, originally described as a B-cell marker, has been revealed as one of the candidate molecular markers of epithelial ovarian cancer. We aimed to determine the pattern and extent of CD24 expression in ovarian serous tumors and to clarify its relationship with pathological parameters, especially those associated with the early events of tumor progression in serous tumors of borderline malignancy. METHODS: A total of 114 ovarian serous tumors, including 9 adenomas, 34 borderline, and 71 carcinomas, were analyzed immunohistochemically using a CD24 monoclonal antibody on paraffin blocks. RESULTS: In normal epithelium and serous cystadenomas, the CD24 expression was localized to the apical membranous portion. In some of borderline tumors (26.4%), additional cytoplasmic expression was observed. The cytoplasmic expression of CD24 in borderline tumors was associated with microinvasion (P = 0.001) and omental implants (P = 0.033) with statistical significance. Serous adenocarcinomas showed strong diffuse cytoplasmic expression of CD24, which was significantly associated with shortened survival rate both in univariate (P = 0.011) and multivariate (P = 0.009) analysis. CONCLUSION: The loss of apical localization with the acquisition of the cytoplasmic staining of CD24 protein is a surrogate marker of stromal invasion in ovarian serous tumors of borderline malignancy. Furthermore, the increase in the cytoplasmic expression of CD24 protein is a strong independent molecular marker for shortened survival rate of patients with ovarian serous adenocarcinomas.     

Loss of expression and altered localization of KAI1 and CD9 protein are associated with epithelial ovarian cancer progression

OBJECTIVE: Impairment of cell adhesion plays a vital role in tumor progression. E- and N-cadherin, CD9, and KAI1 are all adhesion molecules that have been implicated in the progression of several different tumor types. To help explain the potential role these adhesion molecules have in ovarian cancer, comparisons were made between expression patterns in normal ovary and various grades of primary and metastatic epithelial ovarian cancers. METHODS: Thirty-two primary and 8 metastatic human ovarian epithelial carcinomas and 18 samples of normal ovarian tissue were examined for adhesion molecule expression using immunohistochemistry. RESULTS: KAI1 and CD9 revealed an inverse relationship between tumor grade and expression levels, characterized by high expression in low-grade tumors and low expression in high-grade tumors and metastases. KAI1 and CD9 also demonstrated a shift in cellular localization from the membrane in grade 1 tumors to the cytoplasm in grade 3 tumors. N-cadherin expression showed a positive trend between expression levels and tumor grade. E-cadherin expression varied little between different tumor grades and metastases. Inclusion cysts (n = 6) and surface invaginations often strongly expressed KAI1, CD9, and E-cadherin. KAI1 expression was variable in ovarian follicles and corpora lutea depending on their stage of development. CONCLUSIONS: Although sample size is limited, these findings suggest that progression of ovarian epithelial carcinomas is associated with down-regulation and altered cellular localization of KAI1 and CD9. In addition, variable KAI1 expression during follicular and luteal development suggests that it has a physiological function in the ovary. Further investigation will be needed to see if it is also regulated this way during progression of ovarian cancers.     

Upregulation of bikunin in tumor-infiltrating macrophages as a factor of favorable prognosis in ovarian cancer

OBJECTIVE: This study was carried out to clarify the localization of bikunin, a Kunitz-type protease inhibitor, and relation between expression of individual bikunin protein and ovarian cancer progression. METHODS: We performed a retrospective study on the immunohistochemical expression of bikunin, urokinase-type plasminogen activator (uPA) and macrophages (CD68) in surgical specimens derived from 89 ovarian cancer patients to investigate correlations between the expression of bikunin and the clinicopathologic features and the prognosis. Furthermore, bikunin and uPA levels were measured by immunoblot analysis. RESULTS: Immunohistochemical staining revealed that the localization of bikunin was similar to that of CD68 for macrophages. We identified high expression of bikunin in 40 (45%) of 89 ovarian cancers. The results of Western blot analysis showed a significant correlation with immunohistochemical data. There was a significant inverse correlation between bikunin levels and uPA levels in ovarian cancer tissues. High bikunin expression was an independent predictor for disease-free survival (P = 0.040) and overall survival (P = 0.042). The 5-year survival rate of the 49 patients with low bikunin expression in ovarian cancers was 39%, whereas that of the other 40 patients with high bikunin expression was 63%. In addition, macrophage-derived bikunin protein was induced by exogenous IL-6. CONCLUSION: Bikunin derived from tumor-infiltrating macrophages might be a prognostic indicator as an antiinvasive factor supplied from macrophages within and around the tumor possibly through down-regulation of tumor-associated uPA expression.     

基于Oncomine数据库荟萃分析CD24在卵巢癌中的表达和临床意义

目的：探讨CD24在卵巢癌中的表达及意义。方法：收集Oncomine数据库中关于CD24的数据信息，并对目前数据库中资料进行二次分析，对其在卵巢癌中的作用进行统计分析。利用Kaplan-Meier Plotter进行患者生存周期分析。结果：从数据库中纳入不同肿瘤类型研究共计353项，其中64项研究存在CD24表达统计学差异（含高表达研究41项及低表达研究23项）。经过筛选，涉及CD24在正常卵巢组织和卵巢癌组织表达差异的研究共7项（包含5 149例样本），与对照组相比，CD24在367例卵巢癌标本中高表达（P＜0.05）。CD24表达量与卵巢癌总体生存率呈负相关，CD24表达水平越高则患者总体生存率越低（P＜0.05）。进一步亚组分析发现，卵巢子宫内膜样腺癌和卵巢浆液性囊腺癌患者中CD24高表达组的总体生存率较差，而低表达组的总体生存率较好。结论：CD24在卵巢癌组织中高表达，且与卵巢癌预后有关，可能为肿瘤药物的开发提供重要理论依据。     

Expression of platelet-derived growth factor and activated receptor in clinical specimens of epithelial ovarian cancer and ovarian carcinoma cell lines

OBJECTIVES: We determined the expression of platelet-derived growth factor (PDGF), PDGF-receptor (PDGF-R), and phosphorylated PDGF-R (p-PDGF-R) on tumor cells and tumor-associated endothelial cells in clinical specimens of human ovarian carcinoma and human ovarian cancer cells growing in culture and in the peritoneal cavity of nude mice. METHODS: Ten specimens of high-grade serous ovarian carcinoma were analyzed using immunohistochemistry (IHC). IHC was used to detect ligand and receptor expression in the human ovarian cancer cells from Hey A8 and SKOV3ip1 growing in culture. Cells from these lines were also implanted orthotopically into the peritoneal cavity of nude mice. IHC was used to determine ligand and receptor expression in tumors that formed in the peritoneal cavity. RESULTS: All 10 evaluable samples expressed both PDGF AA and BB on tumor cells. Tumor cells were positive for PDGF-Ralpha in 10/10 samples, PDGF-Rbeta in 8/10 samples, p-PDGF-Ralpha in 6/10 samples, and p-PDGF-Rbeta in 4/10 samples. p-PDGF-Ralpha was positive in 4/10 tumor-associated endothelial cell samples and p-PDGF-Rbeta was positive in 3/10 samples. Human ovarian cancer cells expressed PDGF, PDGF-R, and p-PDGF-R when growing in culture or in the peritoneal cavity of nude mice. PDGF-R and p-PDGF-R were also present on tumor-associated endothelial cells as demonstrated by simultaneous staining with CD31 antibody. CONCLUSIONS: PDGF and the corresponding receptors were expressed in autochthonous human ovarian cancer lesions on both tumor cells and tumor-associated endothelial cells. The ligand and receptor were also present on Hey A8 and SKOV3ip1 human ovarian cancer cells growing in vitro and in the peritoneal cavity of nude mice.     

Somatic mitochondrial DNA mutations in primary and metastatic ovarian cancer

OBJECTIVE: To date, most mtDNA mutations in cancer have been identified in the control region (D-loop) containing the major promoters. However, almost all studies used one sample per tumor and there is no clear evidence whether metastatic deposits harbor different mtDNA variants. To establish whether different mtDNA variants can be found in the same cancer but at different sites, we analyzed a series of unilateral and bilateral primary epithelial ovarian cancers as well as paired metastatic tumor deposits. METHODS: We sequenced the D-loop region in 52 different tumor samples of 35 ovarian cancer cases, as well as matched normal tissues. Seventeen of those 35 cases had bilateral ovarian cancer, with a sample from each tumor analyzed. RESULTS: Eighty-six polymorphisms (4 new in ovarian cancer) were detected, and 9 different somatic mtDNA mutations were found in 26% (9 of 35) of ovarian cancer cases; all were homoplasmic in nature. Six of the mutations were novel in ovarian cancer. In 24% (4 of 17) of cases with bilateral ovarian tumors, different mtDNA variants were found between paired tumors, suggesting the presence of different clonal populations of cancer cells. Metastatic tumor deposits showed identical mtDNA variants to those found in at least one of the ovarian tumors in cases with bilateral ovarian cancer. CONCLUSION: Our data demonstrate that multiple tumor samples from the same patient may harbor different mtDNA variants.