67例颅内星形细胞肿瘤临床病理分析

目的：探讨颅内星形细胞肿瘤的组织类型、分级与复发、预后的关系。方法：对６７例颅内星形细胞肿瘤的临床和病理资源进行统计分析。结果：免疫组织化学标记能帮助鉴定组织类型和颅内星形细胞肿瘤的分化程度。间质性星形细胞瘤和胶质母细胞瘤其术后２年、５年的生存率偏低（Ｐ〈０．００５）。结论：间变性星形细胞瘤和肥胖细胞星形细胞瘤更具恶性,易复发。胶质母细胞瘤在颅内肿瘤中恶性程度最高,预后差。     

核转录因子FOXP3蛋白在人脑星形细胞肿瘤组织中的表达及临床意义

目的:检测星形细胞肿瘤组织中FOXP3蛋白的表达,探讨星形细胞肿瘤组织中FOXP3的表达与临床病理特征以及预后的关系。方法:应用免疫组织化学技术检测121例星形细胞肿瘤和5例脑膜瘤,5例正常脑组织中FOXP3的表达。分析FOXP3的表达与星形细胞肿瘤各临床病理参数及预后的关系。结果:FOXP3蛋白在人脑星形细胞肿瘤组织中有表达,在脑膜瘤和正常脑组织中均未见表达,FOXP3蛋白主要表达于间质淋巴细胞的细胞核。在星形细胞肿瘤中,FOXP3的表达在各级别星形细胞肿瘤中表达差异显著(P0.05)。Kaplan-Meier生存分析提示FOXP3阳性组和阴性组生存时间差异显著(P0.01),但COX多因素变量分析结果显示,FOXP3不是影响星形细胞肿瘤患者术后生存时间的独立预后因素(P0.05)。结论:FOXP3在星形细胞肿瘤间质淋巴细胞中的表达与星形细胞肿瘤的恶性程度以及病人的年龄相关。FOXP3阳性的星形细胞肿瘤的预后较FOXP3阴性的星形细胞肿瘤差,但不能作为影响星形细胞肿瘤生存时间的独立预后因素。FOXP3可能成为星形细胞肿瘤免疫调节的新靶点。     

肠道恶性淋巴瘤CT和MRI诊断

目的 探讨肠道恶性淋巴瘤的CT和MRI特征表现及其诊断价值。方法 分析12例肠道恶性淋巴瘤的CT和MRI检查资料。全部病例经手术或活检病理证实，均为非何杰金恶性淋巴瘤。结果 本组12例共发现不连续肠道病变16个。浸润型病灶10个，其中“动脉瘤样扩张征”5个；肠壁非均匀性增厚型病灶2个；肿块型病灶4个。腹腔淋巴结肿大12例。脾受侵犯4例。结论 肠道恶性淋巴瘤的CT和MRI表现具有一定特征性，CT和MRI在显示肠管壁增厚的程度、形态、范围，浆膜面的改变，肠外器官的侵犯，淋巴结增大等方面能提供更详细的影像学资料。有助于肿瘤的定性、分期及疗效评价。     

血管内皮生长因子与脑星形细胞肿瘤血管形成及预后的相关性

目的：探讨血管内皮生长因子（VEGF）与脑星形细胞肿瘤的病理分级,微血管密度（MVD）及预后的关系。方法：应用免疫组化S-P法检测48例脑星形细胞肿瘤标本中VEGF蛋白的表达。结果：在正常脑组织中未见VEGF阳性染色,而在脑星形细胞肿瘤中VEGF阳性率为45.83%,在低级别（Ⅰ、Ⅱ）与高级别（Ⅲ、Ⅳ）,以及术后不同生存情况的患者,其表达差异具有统计学意义,并且其阳性程度与MVD具有相关性。结论：VEGF在脑呈形细胞肿瘤的形成与发燕尾服过程中起一定作用。它可促进瘤组织内微血管的发生,并对其预后判断有指导意义。     

卵巢肿瘤的MRI诊断与鉴别诊断

目的 分析和总结良恶性卵巢肿瘤的MRI表现，提出良恶性卵巢肿瘤的诊断和鉴别诊断价值。方法 分析了39例经手术和病理证实的卵巢肿瘤的MRI资料，包括良性肿瘤22例，恶性肿瘤17例，并与病理结果对照。结果 术前MRI诊断的39例卵巢肿瘤中单侧病灶25例，双侧病灶14例，卵巢病灶共53个。术前诊断卵巢良性肿瘤38个，恶性肿瘤15个。术后病理诊断良性肿瘤36个，恶性肿瘤17个。结论 ①MRI有良好的组织对比分辨率，对畸胎瘤、卵巢子宫内膜异位囊肿、卵巢囊肿、囊腺瘤等病变可以作出定性诊断。②MRI能准确显示卵巢肿块的大小、形态和侵及范围，有助于定性诊断和区分肿瘤的良恶性。     

脑星形细胞瘤微血管密度与临床病理的关系

目的：探讨星形细胞瘤微血管密度与其临床病理的关系。方法：采用免疫组织化学S－P法，对血管内皮细胞行第八因子相关抗原（FⅧRAg）染色，然后测定微血管密度（MVD）。结果：MVD与患者性别、肿瘤生长部位、大小无明显相关；不同病理组织学级别间MVD差异有显著性（P＜0.05)，病理级别越高，MVD越大；瘤周水肿程度不同的星形细胞瘤之间，MVD差异有显著性（P＜0.01)；复发患者MVD高于未复发患者（P＜0.01)。结论：星形细胞瘤MVD与病理级别、术后复发及瘤周组织水肿关系密切，可作为一项有意义的预后指标。     

星形细胞瘤中HMGN5的表达及与临床病理因素的关系

目的探讨高迁移率族蛋白N5(high mobility group N5,HMGN5)在星形细胞瘤中的表达及其与星形细胞瘤患者临床病理因素的关系。方法选取2007-2011年间星形细胞瘤术后石蜡标本117例,WHO组织学分级I-IV级,通过免疫组织化学染色检测HMGN5在星形细胞瘤中的表达水平。应用卡方检验统计HMGN5的表达与患者临床病理因素的关系,Kaplan-Meier分析HMGN5的表达与患者预后的关系。收集6例星形细胞瘤和2例正常脑组织标本,用Western blot检测HMGN5的表达。结果 HMGN5在部分星形细胞瘤中异常高表达(58/117),并且其高表达与肿瘤体积、WHO分级及Ki-67指数呈正相关(P0.001),而与年龄、性别和肿瘤的发生部位没有明显关系(P0.05)。Kaplan-Meier曲线表明HMGN5的高表达与星形细胞瘤患者不良预后正相关(P0.001),Western blot结果显示HMGN5在肿瘤组织中的表达水平与WHO分级正相关。结论 HMGN5可能在星形细胞瘤的发生发展中发挥作用。     

267例子宫内膜癌的预后因素分析

目的探讨影响子宫内膜癌患者生存及预后的因素。方法回顾性总结中山大学肿瘤医院妇科自2000年1月至2004年1月收治的经手术治疗的267例子宫内膜癌患者的临床病理资料和随访结果,进行生存分析及预后的影响因素分析。结果267例患者3年生存率、5年生存率分别为90．8％、88．1％,单因素分析显示：手术-病理分期、病理分级、组织学类型、肌层浸润深度、淋巴结转移、附件转移、术后是否治疗、ER和PR表达与预后有显著性相关（P〈0．05）。经多因素分析后得出,手术-病理分期、病理分级、组织学类型、PR表达4个因素对子宫内膜癌患者的总生存率均产生显著性影响（P〈0．05）。结论子宫内膜癌的5年生存率较高。手术-病理分期、病理分级、组织学类型、PR表达情况是影响预后的独立因素。     

星形细胞肿瘤p53蛋白和PCNA免疫组化及其临床病理意义

应用免疫组化和图象分析技术对人脑星形细胞肿瘤中抑癌基因ｐ５３蛋白（４７例）和增殖细胞核抗原（ＰＣＮＡ）（９７例）的定位、分布及反应强度与分级和预后的关系进行了研究。结果显示；３种ｐ５３蛋白抗体的阳性率为２３．４％～６６．７％，其中ＣＭ－１抗体阳性率高于ｐＡｂ１８０１和ｐＡｂ２４０；ｐ５３表达水平在Ⅱ～Ⅳ级高于１级，并与ＰＣＮＡ标记指数之间相关。ＰＣＮＡ反应强度既与分级相关，又与预后相关，对于分析星形细胞瘤增殖活性和恶性程度有重要意义。     

非霍奇金淋巴瘤中的微血管密度及其临床病理意义

目的：探讨非霍奇金淋巴瘤(NHL)中的微血管密度(MVD)及其与NHL恶性程度、免疫学类型、预后的关系；方法：采用生物素标记的荆豆凝集素I(Bio-UEA-I)免疫组化ABC法对102例NHL的MVD进行原位观察和数量分析；结果：MVD随NHL恶性程度的增高而增高，高度恶性组和中度恶性组MVD显著高于低度恶性组MVD；T细胞性NHL中的MVD显著高于B细胞性NHL的MVD；短生存期组的MVD显著高于长生存期组的MVD；结论：NHL中的MVD可作为判断肿瘤恶性程度、免疫学类型及预后估计的有意义的指标，在临床病理中有实际应用价值。     

Vascular endothelial growth factor and neovascularization in astrocytic tumors

It has been widely recognized that the vascular structure is an important factor when making a histopathological diagnosis and assessing the malignancy potential, especially of astrocytic tumors. The vascular endothelial growth factor (VEGF), which is thought to be regulated by the p53 gene, is a regulation factor for tumor neovascularization. The relationship between VEGF distribution and neovasculature was studied in 42 cases of astrocytic tumors (grades 1–4), which were obtained from surgical material, and the St Anne-Mayo grading system was applied. The relationship between the labeling indices (LI) of VEGF and LI of p53 protein in tumor cells was also studied using immunohistochemistry. The VEGF LI in high-grade malignancy potential tumors, such as grade 3 and grade 4 tumors, was significantly higher than those that were low grade. In grade 4 tumors, a significant correlation between the VEGF LI and the proliferation indices of endothelial cells of neovasculatures was observed. No significant correlation was noted between p53 LI and VEGF LI, as well as p53 LI and histopathological grade. In astrocytic tumors, expression of VEGF may be correlated to tumor neovascularization, and can be considered as an indicator of malignancy potential in astrocytic tumors.     

Expression of mos in astrocytic tumors and its potential role in neoplastic progression

The c-mos gene and its protein product mos, components of the mitogen-activated protein kinase transduction pathway, are known to be involved in the control of meiosis and mitosis. Apart from a study on lung carcinomas, there is little information about its role in human neoplasia. The aim of this study was to investigate expression of mos in astrocytic tumors and to correlate it with accumulation of p53. We studied expression of mos in 62 cases of supratentorial astrocytic tumor. Intracytoplasmic immunostaining for mos was found in 28 (45%) cases: 3 of 20 (15%) grade 2 astrocytomas, 9 of 20 (45%) grade 3 anaplastic astrocytomas, and 16 of 22 (73%) glioblastomas. Immunopositivity for mos correlated significantly (P < 0.01) with tumor grade but not with p53 expression. In contrast to the findings in relation to lung tumors, immunopositivity for mos in astrocytic tumors did not predict recurrence-free or overall survival time. Cytoplasmic immunostaining was observed in scattered large cortical neurons adjacent to tumors, possibly due to stress-induced abortive entry into the cell cycle. The correlation of mos immunopositivity with tumor grade may reflect the expansion of more malignant mos-positive clones. This study provides evidence that mos may be involved in the neoplastic progression of a proportion of astrocytic tumors.     

p34cdc2 in invasive breast cancer: relationship to DNA content, Ki67 index and c-erbB-2 expression

Aims : One-hundred and eighty-eight cases of human mammary carcinoma were examined immunohistochemically for their expression of Ki67, p34^cdc2 and c-erbB-2. DNA image cytometry was performed to evaluate DNA ploidy, Auer type, S-phase fraction (SPF), 5c exceeding rate (5cER) and 2c deviation index (2cDI).  

Methods and results

One-hundred and sixty-eight cases were invasive ductal carcinomas, 20 were of invasive lobular type. Routinely assessed oestrogen and progesterone receptor scores were available. The results were analysed statistically in comparison to tumour type, histopathological grade, lymph node status, menopausal status, patient age and overall survival. Ki67 ( P  < 0.002) and c-erbB-2 ( P  < 0.0001) correlated well with overall survival ( P  < 0.0008) and grade ( P  < 0.038) but not with lymph node status and tumour type. p34^cdc2 showed a trend towards a positive correlation with Ki67 ( P  < 0.058) and a significant negative correlation with receptor status ( P  < 0.008) but with none of the other parameters examined.  

Conclusions

No association between the DNA measured parameters (Auer type, SPF, 5cER and 2cDI) and survival was found. Our results suggest that c-erbB-2 and Ki67 are parameters which might, in combination with receptor status, help to define subgroups with different outcomes.     

Clinical evidence of distinct subgroups of astrocytic tumors defined by comparative genomic hybridization

In astrocytic tumors, the relationship between genetic pathways and patients' prognoses has not been fully investigated. In our studies of astrocytic tumors using comparative genomic hybridization, the presence of 8q gain was mutually exclusive of 7p gain or amplification. In this study, 45 cases of astrocytic tumor were divided into 3 groups: those with 7p gain, cases with 8q gain, or those with neither; and their clinical course, p53, and epidermal growth factor receptor (EGFR) expressions and proliferative activity were then compared. Of the cases examined, 17 (12 glioblastomas and 5 anaplastic astrocytomas) showed 7p gain. Eleven cases (5 glioblastomas, 2 anaplastic, and 4 low-grade astrocytomas) showed 8q gain. p53 accumulation was observed more frequently in cases with 8q gain than in those with 7p gain. Astrocytic tumors with 8q gain occurred more frequently in younger patients than those with 7p gain. Kaplan-Meier survival rate analysis showed higher survival rates in patients with 8q gain than in those with 7p gain. This tendency also was observed when only patients with malignant glioma were included in the survival analysis. Our results provide evidence for distinct clinical manifestations in astrocytic tumors with 8q and 7p gain.     

Expression of the lysosomal-associated membrane protein-1 (LAMP-1) in astrocytomas

Targeting of lysosomes is a novel therapeutic anti-cancer strategy for killing the otherwise apoptosis-resistant cancer cells. Such strategies are urgently needed for treatment of brain tumors, especially the glioblastoma, which is the most frequent and most malignant type. The aim of the present study was to investigate the presence of lysosomes in astrocytic brain tumors focussing also on the therapy resistant tumor stem cells. Expression of the lysosomal marker LAMP-1 (lysosomal-associated membrane protein-1) was investigated by immunohistochemistry in 112 formalin fixed paraffin embedded astrocytomas and compared with tumor grade and overall patient survival. Moreover, double immunofluorescence stainings were performed with LAMP-1 and the astrocytic marker GFAP and the putative stem cell marker CD133 on ten glioblastomas. Most tumors expressed the LAMP-1 protein in the cytoplasm of the tumor cells, while the blood vessels were positive in all tumors. The percentage of LAMP-1 positive tumor cells and staining intensities increased with tumor grade but variations in tumors of the same grade were also found. No association was found between LAMP-1 expression and patient overall survival in the individual tumor grades. LAMP-1/GFAP showed pronounced co-expression and LAMP-1/CD133 was co-expressed as well suggesting that tumor cells including the proposed tumor stem cells contain lysosomes. The results suggest that high amounts of lysosomes are present in glioblastomas and in the proposed tumor stem cells. Targeting of lysosomes may be a promising novel therapeutic strategy against this highly malignant neoplasm.     

Supratentorial Pilocytic Astrocytomas, Astrocytomas, Anaplastic Astrocytomas and Glioblastomas are Characterized by a Differential Expression of S100 Proteins

The levels of expression of the S100A1, S100A2, S100A3, S100A4, S100A5, S100A6 and S100B proteins were immunohistochemically assayed and quantitatively determined in a series of 95 astrocytic tumors including 26 World Health Organization (WHO) grade I (pilocytic astrocytomas), 23 WHO grade II (astrocytomas), 25 WHO grade III (anaplastic astrocytomas) and 21 WHO grade IV (glioblastomas) cases. The level of the immunohistochemical expression of the S100 proteins was quantitatively determined in the solid tumor tissue (tumor mass). In addition twenty blood vessel walls and their corresponding perivascular tumor astrocytes were also immunohistochemically assayed for 10 cases chosen at random from each of the four histopathological groups. The data showed modifications in the level of S100A3 protein expression; these modifications clearly identified the pilocytic astrocytomas from WHO grade II-IV astrocytic tumors as a distinct biological group. Modifications in the level of S100A6 protein expression enabled a clear distinction to be made between low (WHO grade I and II) and high (WHO grade III and IV) grade astrocytic tumors. Very significant modifications occurred in the level of S100A1 protein expression (and, to a lesser extent, in their of the S100A4 and S100B proteins) in relation to the increasing levels of malignancy. While the S100A5 protein was significantly expressed in all the astrocytic tumors (but without any significant modifications in the levels of malignancy), the S100A2 protein was never expressed in these tumors. These data thus indicate that several S100 proteins play major biological roles in human astrocytic tumors.     

4-1BBL分子在脑胶质瘤组织中的表达及其临床意义

目的:探讨共刺激分子4-1BBL(CD137L)在胶质瘤组织中的表达及其临床意义。方法:免疫组化方法检测4-1BBL在82例脑胶质瘤组织中的表达,并分析其与病理分级、患者年龄、性别及生存时间的关系。结果:正常3例脑组织标本未见4-1BBL表达。82例胶质瘤标本31例4-1BBL阳性,阳性表达率为37.8%。统计学提示组织标本中4-1BBL表达与病理级别无明显相关性,与年龄有关(P0.05),4-1BBL阳性患者生存期更长(P0.05)。结论:4-1BBL在部分胶质瘤组织中有表达,其表达对判断胶质瘤患者的预后有一定的参考价值。     

Mucoepidermoid tumors of salivary glands. A long term follow-up study

Mucoepidermoid tumors of salivary glands are relative rare and it has often been difficult to correlate the pathologic features and clinical aspects. The literature recommends long term follow-up studies. The object of the present study was therefore to follow this recommendation. The clinico-pathological features of 39 mucoepidermoid tumors are presented. The material was retrieved from the files of the pathological institute, Rigshospitalet, Copenhagen, during the period 1941-75. All patients, 24 males, 15 females, were followed for a minimum of 5 years. The lesions were classified into low grade (13 cases), intermediate grade (14 cases) and high grade (12 cases). The corresponding 5, 10 and 15 years cumulative survival rates were 92%, 92%, 92% for low grade, 47.4%, 47.4%, 35.5% for intermediate grade and 0%, 0%, 0% for high grade tumors. Thus we found a close correlation between pathology and clinical course. Furthermore, a 5 year observation period appeared an acceptable approach, because 17 of the 18 patients who succumbed of the disease, did so within 4 years following surgery. We consider all grades of mucoepidermoid tumors to be potential malignant. In our study one patient with a low grade tumor died of the disease.     

CD44s和CD44v6在宫颈鳞癌中表达及其临床意义

目的：探讨宫颈鳞癌中CD44s和CD44v6的表达及其与临床病理资料的关系。方法：应用免疫组化EnVision两步法对31例宫颈鳞标本中CD44s和CD44v6蛋白表达并进行分析。结果：肿瘤原发灶中CD44s阳性表达率为61．3％（19／31）。CD44v6阳性表达率为93．5％（29／31）,CD44v6阳性率高于CD44s,CD44s阳性表达与临床分期,病理分级和分类无关（P＞0．05）,CD44v6阳性表达与肿瘤细胞分化程度无关,但与浸润程度及分期有关（P＜0．05）,结论：CD44v6基因蛋白与宫颈鳞癌的侵袭,转移相关,可作为预测肿瘤进展和预后的一种有用指标。     

Correlation between grade and prognosis in metastatic gastroenteropancreatic neuroendocrine tumors

Three-tiered grading systems (low, intermediate, and high grade) have been proposed for neuroendocrine tumors. These classifications have not been rigorously evaluated in neuroendocrine malignancies of the digestive tract. We performed a retrospective chart analysis of 83 patients with metastatic gastroenteropancreatic neuroendocrine tumors, correlating tumor grade with overall survival. We also analyzed available biopsy specimens (on 40 patients), examining hematoxylin and eosin stains for mitotic rate and immunostaining for measurement of the Ki-67 index. Tumor grades were assigned based on the mitotic rate and the Ki-67 index, and the prognostic validity of each grading method was assessed. A highly significant correlation existed between the reported tumor grade and overall survival. Five-year survival rates for patients with low-, intermediate-, and high-grade tumors were 87%, 38%, and 0%, respectively. On biopsy specimen analysis, both mitotic rates and Ki-67 indexes correlated strongly with overall survival. We conclude that a 3-tiered grading classification for gastroenteropancreatic neuroendocrine tumors correlates with survival in the metastatic setting. Both mitotic rates and Ki-67 indexes are inversely associated with survival and can be analyzed independently for assignment of grade.