VEGF-C表达和微淋巴管密度与胃癌淋巴转移的关系及意义

目的探讨胃癌组织血管内皮生长因子C(VEGF-C)表达和微淋巴管密度(MLVD)及两者与胃癌淋巴转移的关系。方法应用免疫组织化学方法检测208例人胃癌组织、40例癌浸润前缘组织及139例人胃正常粘膜组织中VEGF-C、D2-40的表达,对D2-40阳性脉管进行MLVD计数,并结合病理资料进行统计学分析。结果胃癌组织VEGF-C的表达明显高于正常胃粘膜组织(χ2=109.199,P<0.01);胃癌组织中有淋巴结转移(χ2=14.496,P<0.01)或浸润透浆膜(χ2=11.586,P<0.01)组VEGF-C表达水平分别较无转移或浸润未及浆膜组增高。癌浸润前缘组织中MLVD(18.36±15.60个/mm2)明显高于胃癌组(9.41±9.32个/mm2,t=-3.681,P<0.01)和胃正常粘膜组织(7.70±7.69个/mm2,t=-4.180,P<0.01);胃癌淋巴结转移组MLVD(9.81±9.97个/mm2)高于无转移组(6.41±7.85个/mm2,t=2.516,P<0.01),而在浸润透浆膜组(11.20±10.55个/mm2)和未及浆膜组(8.54±9.36个/mm2)MLVD无差别(t=1.467,P=0.472)。另外,在胃癌组织中VEGF-C表达与MLVD呈正相关(F=2.910,P<0.05)。结论VEGF-C在胃癌中的高表达与胃癌浸润深度、淋巴转移密切相关。     

Expression,Localization, and Phosphorylation of Akt1 in Benign and Malignant Thyroid Lesions

The serine/threonine protein kinase Akt is a key molecule in the phosphatidyl inositol 3-kinase pathway that is often overactivated in human cancers. Three Akt isoforms (Akt1, Akt2, Akt3) have been identified in human cells and they show different distribution and have non-redundant functions. The aim of this study was to determine whether the expression, phosphorylation, and localization of Akt1 isoform in human thyroid malignant lesions are different from those in benign lesions. Nuclear and cytoplasmic fractions were isolated from tissue samples and Western blot method was used to detect Akt1 presence in both cellular fractions. Akt1 expression was also assessed by ELISA method. To estimate Akt1 phosphorylation, kinase was immunoprecipitated from cell lysates and tested with anti-phospho-Akt antibodies. The Akt1 expression in majority of thyroid cancer samples was significantly higher than in benign lesions (p < 0.05). Akt1 both in differentiated cancers (follicular and papillary) and benign lesions was localized mainly in cytoplasmic fraction. In two of three anaplastic cancer samples Akt1 was predominantly localized in nucleus. The ratio of phosphorylated Akt1 to total Akt1 was lower in cancers than in non-neoplastic lesions and adenomas. Thus, although Akt1 seems to be overexpressed in thyroid neoplasms, its high phosphorylation is not characteristic for thyroid cancers.     

An Immunohistochemical Study of Cytokeratin and Vimentin in Benign and Malignant Thyroid Lesions

Intermediate filaments in benign and malignant thyroid lesions were immunohistochemically studied using polyclonal and monoclonal anti-cytokeratin (CK), and monoclonal anti-vimentin antibodies. Antigenicity of CK and vimentin was almost completely destroyed during formalin fixation in normal thyroid and all thyroid lesions except for some cases of papillary and squamous cell carcinoma, although the latter showed negative immunostaining with anti-vimentin antibody. In sections fixed with Carnoy's fixative, most cases of papillary carcinoma showed an intense reaction product for polyclonal anti-CK, monoclonal anti-CK-7, CK-19 and anti-vimentin antibodies. The reaction product for anti-CK antibodies was located mainly in the apical cytoplasm and that for anti-vimentin antibody in the basal cytoplasm. However antigenicity was still destroyed by the fixative in many specimens of normal thyroid, benign thyroid lesions and follicular carcinoma. In frozen sections, all specimens showed preserved antigenicity for both antigens with an intense reaction product in papillary carcinoma, but this was weaker in normal thyroid, benign thyroid lesions and follicular carcinoma. Therefore, follicular cells under normal and pathological conditions contain intermediate filaments of CK and vimentin in their cytoplasm and co-expression of the antigens is significantly increased in papillary carcinoma.     

An Immunohistochemical Study of Calcitonin–containing Cells in Benign and Malignant Thyroid Lesions

Parafollicular cells (C-cells) in benign and malignant thyroid lesions were studied immunohistochemically with a polyclonal anti-calcitonin (CT) antibody. The C-cells were seen most frequently in the middle third of the lateral lobes in the thyroid gland of normal individuals and patients with Graves' disease and chronic thyroiditis, although in the latter the number of such cells was significantly decreased (p< 0.05). In adenomatous goiter, C-cells were present in nodular lesions from an early stage of nodule development (frequency about 19%), whereas in the later stage these cells were rarely observed inside type 1 nodules, which were generally characterized by an admixture of follicles with considerably different sizes. However, C-cells were not observed inside type 2 nodules, which were composed of similar-sized follicles, or in the parenchyma of 56 cases of benign and malignant thyroid tumors. These findings suggest that since C-cells are present in nodular lesions, the histogenesis of adenomatous goiter is quite different from that of follicular adenoma; thyroid neoplasms generally contain no C-cells in the parenchyma. Acta Pathol Jpn 40: 187-192, 1990.     

三阴乳腺癌组织表皮生长因子受体表达及其与微血管密度和微淋巴管密度的相关性

目的:检测表皮生长因子受体(EGFR)在三阴乳腺癌(TNBC)患者癌组织中的表达及与癌组织中微血管密度(MVD)和微淋巴管密度(MLVD的相关性。方法:应用免疫组化法检测48例TNBC癌组织EGFR表达及MVD和MLVD,分析EGFR的表达程度与MVD和MLVD的相关性。结果:TNBC患者癌组织中的EGFR阳性表达率为66.67%(32/48),其中(+)和(++)者各4例(8.33%),(+++)者9例(18.75%),(++++)者15例(31.25%),EGFR阳性表达与其MVD和MLVD呈显著正相关(P0.01)。结论:TNBC癌组织高表达EGFR及高MVD和高MLVD,从而影响肿瘤生物学行为及患者预后;抗EGFR靶向治疗可能使患者获益。     

AKT-1在乳腺良恶性病变中的表达及其临床意义

目的通过研究AKT-1在乳腺癌、癌旁正常组织、乳腺纤维腺瘤中的表达情况,探讨其在乳腺癌评估预后及治疗方面的价值。方法采用免疫组化SP法,检测61例乳腺癌、20例癌旁正常组织、20例乳腺纤维腺瘤中AKT-1的表达情况。结果 AKT-1在乳腺癌旁正常组织中无表达,在纤维腺瘤中低表达(阳性率为15%),在乳腺癌组织中高表达(阳性率为49.2%),差异具有统计学意义(P<0.05)。在乳腺癌组中,AKT-1的阳性表达率与HER-2表达情况呈正相关;在原发灶大小不同、腋窝淋巴结有无转移和TNM分期不同组中,AKT-1的阳性表达率差异有统计学意义(P<0.05);在不同年龄、不同雌孕激素受体情况和不同组织学类型中,差异无统计学意义(P>0.05)。结论 AKT-1可能是导致乳腺癌发生、发展的因素之一,在乳腺癌细胞向周围组织浸润,远处转移中起一定作用,对判断乳腺癌的恶性程度及预后有重要意义。     

Giant Mitochondria and Intramitochondrial Inclusions in Benign Thyroid Lesions

Enlarged mitochondria and intramitochondrial dense structures have been reported to occur in a great variety of animal and human cells under normal, pathologic, and experimental conditions. Three cases of benign thyroid lesions are described in which large cytoplasmic inclusions were seen on light microscopy. These inclusions were stained with toluidine blue but not with Sudan black B, as was seen in consecutive sections. Ultrastructural observation showed that they corresponded to giant mitochondria. Bundles of dense filaments and round, electron-dense bodies were observed in the matrix of the enlarged mitochondria. Incubation of ultrathin sections with proteolytic enzymes (pepsin, trypsin, and type XVI-protease) led to a striking decrease in the electron density of both types of intramitochondrial matrical structures. These observations demonstrate that a major proteic component exists in intramitochondrial filamentous bundles and in dense bodies.     

乳腺良,恶性病变Ki67单克隆抗体标记观察

本文用Ｋｉ６７单克隆抗体对１１例乳腺浸润性导管癌、１０例乳腺良性病变做了研究。结果显示乳癌Ｋｉ６７标记阳性率较高（Ｍ１２．５），良性病变较低（Ｍ８．１５），两者间差异有显著性（Ｐ＝０．０５）。乳癌Ｋｉ６７ 记阳性率与核分裂计数和核面积呈显著正相关（相关系数分别为０．８４９，Ｐ＜０．０１和０．７４０，Ｐ＜０．０１）。未发现与淋巴结转移，肿物大小和年龄之间的相关性（Ｐ＞０．０５）。     

Expression of Simple Mucin Type Antigens and Lewis Type 1 and Type 2 Chain Antigens in the Thyroid Gland: An Immunohistochemical Study of Normal Thyroid Tissues,Benign Lesions,and Malignant Tumors

In order to characterize the pattern of expression of carbohydrate structures in several types of thyroid tissues and to evaluate the putative usefulness of the detection of such antigens in diagnostic surgical pathology, we undertook the immunohistochemical study of simple mucin type antigens (T, Tn, and sialyl Tn), Lewis type I antigens (Lewis a, sialyl Lewis a, and Lewis b), and Lewis type 2 related antigens (precursor type 2, H type 2, Lewis x, sialyl Lewis x, and Lewis y) in thyroid samples obtained from 65 patients. The material consisted on paraffin sections of normal thyroid (n = 43), benign lesions (13 goiters/ hyperplastic lesions and 15 adenomas), and malignant tumors (12 follicular carcinomas and 27 papillary carcinomas, 5 of which had lymph node metastases) of the thyroid follicular epithelium. Tn, T, and precursor type 2 antigens were the only antigens that were detected—and very rarely—in normal thyroid. Benign lesions were similar to normal thyroid despite displaying a higher prevalence of immunoreactivity for severa antigens of the three groups. Thyroid carcinomas presented a significantly higher level of expression of all types of simple mucin, Lewis type 1, and Lewis type 2 antigens than the normal thyroid and benign lesions. The expression of sialyl Tn was restricted to malignant tumors, and the expression of sialyl Lewis x was closely associated, though not exclusively, to papillary carcinomas. The immunoreactivity was stronger and the number of positive cases was higher in papillary than in follicular carcinomas. No differences were found between primary tumors and the respective metastases. The existence of distinct patterns of expression of carbohydrate antigens in different types of thyroid lesions points to the usefulness of the detection of some of these antigens in thyroid surgical pathology. The putative role of such antigens in the peculiar metastatic properties of thyroid carcinomas remains unsettled.     

Isoantigens A, B and H in Benign and Malignant Lesions of Breast

Eighty-five specimens of breast tissue were grouped and investigated by the technic of mixed cell agglutination reation (MCAR) for studying isoantigens A, B and H (O). MCAR was found to be strongly positive at the epithelium of acini in all the 25 subjects with benign lesions (10 fibroadenomas, 10 cystic mastitis and 5 gynecomastias). On the other hand, all the subjects with diagnosis of primary carcinomas in breast (45 subjects) and their metastases (15 subjects) were found to be uniformly negative for any agglutination reaction. In view of these findings, it seemed that the isoantigens in primary and metastatic malignancies of breast are always lost, while in the benign lesions isoantigens are always present. Although the exact mechanism is not understood, it seems that, in malignancies with a glandular differentiation, some differences exist when these are compared to malignancies with a squamous differentiation. The various possibilities are discussed in the light of previous studies.     

直肠腺癌VEGF-C及VEGFR-3的表达与淋巴转移的关系

目的为探讨癌细胞淋巴管转移机理,观察血管内皮生长因子-C(VEGF-C)和血管内皮生长因子受体-3(VEGFR-3)在直肠腺癌组织及淋巴管的表达。方法取人直肠腺癌手术材料30例,用免疫组化方法检测癌区和癌周正常区VEGF-C和VEGFR-3的表达情况。结果VEGF-C主要表达在直肠腺癌的癌细胞胞浆,VEGFR-3主要在淋巴管内皮细胞有阳性表达,两者在癌区的表达率均高于正常区直肠组织;癌区淋巴管的平均面密度(33.81±5.67)高于正常区平均面密度(20.13±3.27)。结论VEGF-C和VEGFR-3在人直肠腺癌中的过表达,可能与淋巴管增生和扩张,促进癌细胞的淋巴转移有关。     

乳腺癌淋巴管LYVE-1和PROX-1表达程度与肿瘤淋巴转移的关联性分析

目的观察乳腺浸润性导管癌患者肿瘤组织中乳腺癌淋巴管LYVE-1和PROX-1的表达程度与肿瘤淋巴转移的关联性。方法选择乳腺浸润性导管癌患者90例为实验组,以60例乳腺良性病变患者为对照组,检测实验组患者肿瘤组织LYVE-1和PROX-1的水平,与对照组患者组织的LYVE-1和PROX-1的水平进行比较;将实验组患者按转移、复发情况进行分类,观察LYVE-1和PROX-1表达与肿瘤淋巴转移的关系。结果实验组患者肿瘤组织的LYVE-1和PROX-1阳性淋巴管密度(LVD)明显高于对照组,实验组患者中有淋巴转移患者的LYVE-1和PROX-1阳性LVD明显高于无淋巴转移患者,差异具有统计学意义(P<0.05);LYVE-1和PROX-1阳性LVD之间无相关性;logistic回归分析,LYVE-1和PROX-1是肿瘤转移的相关因素,对LYVE-1、PROX-1与转移的关系绘制ROC曲线,AUC分别为0.716、0.672;按ROC曲线分析所得诊断临界值进行分组,随访观察一年,LYVE-1、PROX-1阳性LVD升高患者,淋巴转移率较高。结论乳腺浸润性导管癌患者肿瘤组织LYVE-1和PROX-1表达与淋巴管生成有关,表达程度高的患者更易发生淋巴转移。     

促甲状腺激素、甲状腺球蛋白浓度在甲状腺良、恶性结节诊断中的价值

目的 探讨血清促甲状腺激素（TSH）、甲状腺球蛋白（Tg）浓度变化在甲状腺良、恶性结节诊断中临床价值.方法 选取96例因甲状腺结节病住院患者,比较甲状腺良、恶性结节患者血清TSH、Tg浓度差异,分析血清TSH、Tg浓度与甲状腺良、恶性结节的关系.结果 甲状腺恶性结节组血清TSH浓度（2.55±1.46mIU/L）与甲状腺良性结节组（1.15±1.10mIU/L）比较,差异有统计学意义（P＜0.05）;随血清TSH浓度的升高,甲状腺恶变结节比例升高;甲状腺恶性结节组血清Tg浓度（255.0±60.6ng/mL）高于甲状腺良性结节组（115.0±32.4ng/mL） （P ＜0.05）,不同血清Tg浓度组间甲状腺恶性结节数比例差异无统计学意义（P＞0.05）.结论 血清TSH、Tg浓度检测对甲状腺良、恶性结节诊断中有一定临床意义,血清TSH浓度是预测甲状腺结节恶变的危险因子.     

大肠良,恶性病变细胞核DNA含量及AgNORs定量研究

本文对83例大肠良、恶性病变细胞核DNA含量及核仁组成区嗜银蛋白(AgNORs)的定量研究,结果显示:非肿瘤性息肉核DNA含量接近正常粘膜,均为二倍体,腺瘤及腺癌DNA含量依次增高,均明显高于正常粘膜,分别有33.33％(10/30)和69.70％(23/33)的异倍体率。各组AgNORs计数结果也遵循类似的规律,且正常肠粘膜、非肿瘤性息肉、腺瘤及腺癌各组间AgNORs计数无重叠。表明DNA含量分析结合AgNORs计数及形态学观察对大肠肿瘤的早期诊断及良、恶性病变的鉴别有重要的价值。     

血清CEA、 Tg联合检测在甲状腺良、恶性肿瘤中的临床价值

目的 探索血清CEA、Tg联合检测在甲状腺良、恶性肿瘤中的临床价值.方法 采用化学发光法分别检测经病理证实的68例分化型甲状腺癌(DTC)术前和手术联合131I清甲治疗后、65例甲状腺腺瘤、55例正常对照的CEA、Tg水平,并将结果应用SPSS13.0软件进行统计学分析.结果 术前DTC组的CEA水平明显高于腺瘤组(P＜0.05)、Tg水平与腺瘤组差异无统计意义(P ＞0.05);DTC组患者手术联合131I清甲治疗后的Tg水平有显著性下降(P＜0.05);术后Ⅰ和Ⅱ期DTC患者的Tg、CEA水平明显低于Ⅲ和Ⅳ期的(P＜0.05).结论 血清CEA、Tg联合检测对手术及131I清甲治疗后DTC患者的治疗效果及预后判断有较大价值,CEA检测对确诊中晚期的DTC患者有辅助诊断作用.     

联合血液学指标和超声建立甲状腺结节术前良恶性鉴别模型

目的 结合大量临床诊断病例的验证分析,寻找术前甲状腺结节相关指标,建立甲状腺结节良恶性鉴别早期辅助诊断模型.方法 研究解放军总医院收治甲状腺结节住院患者并及时收集其术前血液样本用于生化、甲功、血常规等相关指标测定.回顾性验证分析术前病人一般资料、临床血液学数据、超声结果与术后病理诊断的相关性.结果 入选Logistic回归方程指标包括年龄(Age)、血清促甲状腺激素(TSH)、血清高密度脂蛋白(HDL)、中性粒细胞计数(N)、超声结果(Ult)5项,建模方程为Logit(P)=1.673-0.069X1+0.301X3-1.499X8+5.335X10+ 21.182X12,模型组联合ROC曲线下面积为0.882;验证组为0.812.结论 通过模型分析初步建立甲状腺结节术前良恶性鉴别的血液学指标应用基础,联合超声为手术选择提供客观依据.     

高频超声结合BI-RADS分级在乳腺良恶性病变中的应用价值

目的 探讨高频超声结合BI-RADS分级在乳腺良恶性病变诊断的应用价值。方法 选取2016年3月~2017年10月东莞市石碣镇参与“两癌”筛查乳腺体检者2874例,应用超声检查双乳情况。对2874例乳腺体检者进行随访,其中经穿刺检查或手术切除肿物组织病理检查发现,恶性肿瘤17例。以病理诊断结果为对照,评估高频超声结合BI-RADS分级在乳腺良恶性病变诊断的应用价值。结果 乳腺恶性病变的高频超声高评分的例数高于良性病变,差异有统计学意义（P＜0.05）;乳腺恶性病变BI-RADS评分Ⅳ级例数高于良性病变,差异有统计学意义（P＜0.05）;高频超声评分与BI-RADS分级诊断乳腺病变的灵敏度、特异度、准确率、阳性预测值及阴性预测值之间比较,差异无统计学意义（P＞0.05）;两种方法联合诊断时,其灵敏度、特异度、准确率、阳性预测值及阴性预测值均较单独高频超声评分诊断、单独BI-RADS分级诊断有不同程度的提高,其中两种方法联合诊断时灵敏度和阳性预测值与两种方法单独诊断比较,差异有统计学意义（P＜0.05）。结论 高频超声检查与BI-RADS评分分级在鉴别诊断乳腺肿块良恶性上具有较高的临床价值,但仍存在一定局限性,两者联合应用在一定程度上能提高乳腺良恶性病变的诊断准确率,是较为理想的检查手段。     

Expression of Human Herpesvirus-6 Antigens in Benign and Malignant Lymphoproliferative Diseases

Immunohistochemistry was used to look for the expression of human herpesvirus-6 (HHV-6) antigens in a well characterized series of benign, atypical, and malignant lymphoid lesions, which tested positive for the presence of HHV-6 DNA. A panel of specific antibodies against HHV-6 antigens, characteristic either of the early (p41) or late (p101K, gp106, and gp116) phases of the viral cycle, was applied to the lymphoid tissues from 15 non-Hodgkin’s lymphomas, 14 Hodgkin’s disease cases, 5 angioimmunoblastic lymphadenopathies with dysproteinemia, 14 reactive lymphadenopathies, and 2 cases of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). In lymphomatous tissues, the expression of late antigens was documented only in reactive cells, and mainly in plasma cells. Of interest, the expression of the early p41 antigen was detected in the so-called “mummified” Reed-Sternberg cells, in two Hodgkin’s disease cases. In reactive lymphadenopathies, the HHV-6 late antigen-expressing cells were plasma cells, histiocytes, and rare granulocytes distributed in interfollicular areas. In both cases of Rosai-Dorfman disease, the p101K showed an intense staining in follicular dendritic cells of germinal centers, whereas the gp106 exhibited an intense cytoplasmic reaction in the abnormal histiocytes, which represent the histological hallmark of the disease. The expression of HHV-6 antigens is tightly controlled in lymphoid tissues. The lack of HHV-6 antigen expression in neoplastic cells and the limited expression in degenerating Reed-Sternberg cells argue against a major pathogenetic role of the virus in human lymphomagenesis. The detection of a rather unique pattern of viral late antigen expression in Rosai-Dorfman disease suggests a possible pathogenetic involvement of HHV-6 in some cases of this rare lymphoproliferative disorder.