Nucleostemin mRNA is expressed in both normal and malignant renal tissues

Nucleostemin (NS), a p53-binding protein, has been shown essential for stem and cancer cell proliferation and implicated in oncogenesis. To explore potential contributions of NS to the development of clear cell renal cell carcinomas (ccRCCs), we determined NS expression in ccRCC cell lines, and in paired normal and malignant renal tissues from 31 patients with ccRCC. Nucleostemin mRNA and/or protein expression was observed in all four cell lines and 27 of 31 (87%) tumour specimens. Surprisingly, 16 of 31 (52%) adjacent normal renal samples also expressed NS mRNA and its levels in four of them were comparable with those in paired tumour tissues. Three of the patients had detectable NS mRNA in their normal renal tissues whereas lacked its expression in the matched tumours. Compared to the oncogene c-MYC expression in these same samples, NS expression showed a much less specificity for ccRCC. We further demonstrated that NS mRNA expression was closely associated with cellular proliferation in normal fibroblasts or T lymphocytes and renal cell carcinoma cell lines. Collectively, NS expression widely occurs in normal and malignant renal tissues, and is likely a proliferation marker rather than a unique regulator of cell proliferation and survival in stem and cancer cells.     

Histone H1x is highly expressed in human neuroendocrine cells and tumours

Background  

Histone H1x is a ubiquitously expressed member of the H1 histone family. H1 histones, also called linker histones, stabilize compact, higher order structures of chromatin. In addition to their role as structural proteins, they actively regulate gene expression and participate in chromatin-based processes like DNA replication and repair. The epigenetic contribution of H1 histones to these mechanisms makes it conceivable that they also take part in malignant transformation.     

Primary thymic carcinoma: A clinicopathological and immunohistochemical study

During the treatment of five cases of thymic carcinoma, we conducted a clinicopathological and immunohistochemical study. The patients included four males and one female, whose ages ranged from 50 to 69 years. The histologic breakdown was squamous cell carcinoma in four and small cell carcinoma in one. Immunohistochemically, the squamous cell carcinomas were positive for cytokeratin (intermediate molecular weight) and keratin. However, staining was negative for Leu-7 and chromogranin. A complete resection was achieved in only one case. In all four of the remaining cases, the resection was incomplete due to invasion into adjacent organs and disseminated lesions. Thymic carcinoma is a tumor for which a higher response rate can be expected from multidisciplinary therapy than that for lung cancer. Therefore, it is desirable, from the clinical view, to determine clinical staging and to establish standard operative procedures comprising mediastinal lymph node dissection as well as effective chemotherapy. With respect to pathology, it is hoped that an improved histologic classification will be developed. © 1994 Wiley-Liss, Inc.     

MAD2蛋白在人正常组织和胃癌组织中的表达

目的：研究MAD2蛋白在人正常组织和胃癌中的表达及其临床意义。方法：用免疫组织化学方法检测23例人正常组织及102例胃癌及癌旁组织中MAD2蛋白的表达。结果：MAD2蛋白在23例正常组织中主要定位在胞核和胞浆中,在正常胃组织主要定位在胞浆,在胃癌组织中主要定位在胞核和胞浆。MAD2在胃癌中和癌旁组织的表达阳性率分别为70．59％（72／102）和38．24％（39／102）,两者差异具有统计学意义（P〈0．001）。MAD2蛋白表达与肿瘤组织分化程度呈负相关,与淋巴结转移呈正相关（P〈0．001）。结论：MAD2蛋白在细胞有丝分裂监测点中发挥重要作用,其亚细胞定位在胃癌形成中发生变化,MAD2表达在胃癌发生过程中具有重要作用,对其检测有助于胃癌恶性程度评价和预后判断。     

FAM83A在肺腺癌组织中高表达且促进肺腺癌细胞的侵袭和转移

背景与目的：越来越多的研究表明,序列相似性为83的家族成员A（family with sequence similarity 83 member A,FAM83A）与肿瘤的侵袭和转移相关,但FAM83A在肺腺癌中的作用尚不清楚。探讨FAM83A在肺腺癌组织中的表达情况,与肺腺癌患者预后的关系以及对肺腺癌细胞增殖、侵袭转移能力的影响。方法：运用人类蛋白质图谱（Human Protein Atlas,HPA）和基因表达谱动态分析（Gene Expression Profiling Interactive Analysis,GEPIA）数据库分析并选取与肺腺癌预后相关的基因;运用UALCAN和GEPIA数据库研究FAM83A的表达量对肺腺癌生存率的影响;采用UALCAN数据库分析FAM83A在肺腺癌组织中的表达及其与肺腺癌患者的性别、淋巴结的分期和转移的关系;采用蛋白质印迹法（Western blot）检测人正常肺上皮细胞BEAS-2B和肺腺癌细胞A549中FAM83A蛋白的表达情况及FAM83A的转染效率;采用细胞计数试剂盒（cell counting kit-8,CCK-8）检测转染后敲减FAM83A对肺腺癌细胞增殖能力的影响;采用transwell侵袭实验检测FAM83A对肺腺癌细胞侵袭能力的影响。结果：采用HPA、GEPIA和UALCAN数据库分析发现高表达的FAM83A与肺腺癌不良预后相关且FAM83A在肺腺癌组织中高表达,差异有统计学意义（P<0.05）;FAM83A的表达与肺腺癌的临床分期和淋巴结转移相关;Western blot检测结果显示,FAM83A在肺腺癌细胞中高表达且敲减质粒转染成功;CCK-8细胞增殖实验结果提示FAM83A可促进细胞的增殖能力（P<0.05）;Transwell侵袭实验提示FAM83A促进A549的侵袭能力（P<0.05）。结论：FAM83A在肺腺癌组织和细胞中高表达且促进肺腺癌细胞的增殖、侵袭和转移。     

间变性大细胞淋巴瘤的临床病理与免疫组化研究(附3例报告及文献复习)

目的　研究间变性大细胞淋巴瘤 (ALCL)的临床病理和免疫组化特征。方法　应用免疫组化染色 (SP法 )对 3例ALCL进行免疫表型标记 ,采用了一种新的间变性大细胞淋巴瘤的特异性抗体ALKp80 (间变性淋巴瘤激酶 )。 结果　 3例ALCL的ALKp80均呈强阳性 ,2例CD30 阳性 ,2例LCA阳性 ,2例EMA阳性 ,1例CD685 0 %以上细胞阳性。 3例T、B细胞标记均不表达 ,CD15均呈阴性。结论　ALKp80不仅是ALCL的一个特异性标记物 ,而且对判断ALCL的预后有重要的意义。     

脑内胶质肉瘤1例临床病理及免疫组化研究报道

目的脑内胶质肉瘤为中枢神经系统极为罕见的肿瘤,其恶性程度高,易复发,危害大,临床需与恶性胶质瘤、恶性脑膜瘤相鉴别,本文报道1例发生于68岁女性的病例,通过临床、病理组织学及免疫组织化学染色等技术观察了胶质肉瘤的特点,并探讨其与恶性胶质瘤、恶性脑膜瘤鉴别要点.方法在对该病例手术标本进行病理组织学观察和免疫组织化学、组织化学染色的基础上,结合临床资料并复习文献,探讨胶质肉瘤的组织学特征及标志性蛋白的表达情况.结果在病理形态上,肿瘤组织主要表现为多形性胶质母细胞瘤及肉瘤的共同特征,其中肉瘤区瘤组织排列紧密,瘤细胞呈大小不一的梭形;胶质瘤区瘤组织排列较前者疏松,细胞呈类园形或多角形,瘤组织局部常有坏死、出血.免疫组织化学染色及组织化学染色胶质瘤区GFAP(+)、S-100(±),胶质瘤及肉瘤区Vimintin(+),肉瘤区desmin(-)、actin(±)、CD68(+);网状纤维染色肉瘤区的瘤细胞间有丰富的网状纤维穿插,胶质瘤区未显示明显网状纤维;Masson染色肉瘤区富含胶原纤维.结论胶质肉瘤具有多形性胶质母细胞瘤和肉瘤的特点,通过病理组织学、组织化学及免疫组织化学染色结果可与恶性胶质瘤、恶性脑膜瘤相鉴别,从而为临床诊治提供指导.     

胃肠道间质瘤22例临床病理及免疫组织化学特征

目的探讨胃肠道间质瘤（GIST）的临床表现，病理组织形态学和免疫组织化学特点。方法对22例确诊的胃肠道间质瘤的临床病理资料进行回顾性分析并采用免疫组织化学SP法检测CD117，CD34等抗体的表达。结果本组GIST均为成年人（年龄34～76a）。发生于胃12例，小肠7例，直肠1例，腹膜后2例。常见症状为腹部肿块和腹胀不适，2例胃GIST术后1a有肝转移。镜下观察，基本类型为梭形细胞和上皮样细胞。CD117、CD34及Vimentin多为弥漫阳性，阳性率分别为95．5％、72．7％和68．2％。平滑肌肌动蛋白（SMA）及S-100阳性率分别为27．2％和36．4％。结蛋白及NSE均阴性。恶性组中瘤体与周围组织有粘连，直径〉5cm，核分裂像〉10／50HPF,肿瘤性坏死及细胞密集与交界性良性组有显著差异。结论GIST好发于中老年人，细胞形态结构多样，免疫组织化学特征为CD34和CD117阳性。瘤体直径，核分裂像，肿瘤性坏死及细胞密集程度可作为判断良恶性的参考指标。     

Melanotic schwannoma of the sympathetic ganglia: A histologic,immunohistochemical and ultrastructural study

We describe the case of a 46-year-old male patient who presented withpain in the left thigh, often accompanied by lumbar pain. These symptomswere sustained by a neoplasm, which was located in the sympathetic ganglia,at the level of the 3rd left lumbar spinal root and which was completelyexcised. Immunohistochemical positivity for S100, HMB45, and NSE antibodiessuggested that the lesion was a melanotic schwannoma (MS), with bothschwannian and melanocytic differentiations, the latter containingmelanosomes at ultrastructural examination. Non-recurrence after 16 monthsof follow-up further supports our diagnosis of MS.     

A comparative study of the localization of CEA and NCA2 in cancerous and normal gastrointestinal tissues.

The histological localization of CEA in gastrointestinal tissues was re-evaluated after absorption of anti-CEA antiserum with NCA2, another normal antigen cross-reacting with CEA. This absorbed antiserum showed clearly the presence of CEA in colonic tumors and some non-cancerous colonic mucosae, obtained even from non-cancerous patients. In contrast, some of the gastric adenocarcinomas we studied were strained very weakly by absorbed anti-CEA antiserum, although non-absorbed antiserum (or serum absorbed with NCA alone) labelled them strongly. The same difference in reactivity between both antisera was observed in intestinal metaplasia. The localization of NCA2 was studied with a specific antiserum, previously absorbed with CEA and NCA. NCA2 was found to be a noromal cytoplasmic and mucus-associated antigen of gastrointestinal tissues. It was present also in fetal stomach and colon. Sections of gastric and colonic tumors as well as intestinal metaplasia of gastric mucosae always reacted brilliantly with absorbed anti-NCA2 antiserum.     

慢性食管炎和食管癌旁粘膜上皮癌基因蛋白表达的比较

背景与目的:探讨慢性食管炎增生的粘膜上皮与食管癌旁粘膜上皮3种癌基因蛋白表达的关系.材料与方法:采用免疫组织化学EnVision二步法对47例慢性食管炎及85例食管癌和癌旁粘膜组织进行P53、P27和MDM2蛋白表达的检测.结果:P53蛋白在正常食管粘膜不表达,在食管炎、癌旁非典型增生,食管癌3组阳性率相似,高于正常食管上皮的阳性率;对于P27蛋白阳性反应,4组阳性率相似;MDM2在正常上皮、食管炎、癌旁非典型增生3组阳性率相似,低于食管癌的阳性率.慢性食管炎粘膜上皮P53、P27、和MDM2 3种蛋白表达与癌旁轻、中、重度非典型增生粘膜上皮相似.结论:慢性食管炎食管粘膜上皮P53、P27和MDM2 3种蛋白表达与癌旁粘膜上皮轻、中、重度非典型增生相似,提示慢性食管炎可能是一种癌前病变.     

Splice variants of the cell surface glycoprotein CD44 associated with metastatic tumour cells are expressed in normal tissues of humans and cynomolgus monkeys

Certain isoforms of the CD44 glycoprotein family play an essential role in the metastatic spread of tumour cells. Protein expression of such CD44 isoforms has also been observed in a variety of human malignancies. In this study, we compared the expression of exon v5- and v6-containing CD44 isoforms in normal human and cynomolgus monkey (Macacca fasciculata) tissues. Cloning and sequencing of cynomolgus CD44 exons v5 and v6 revealed a homology of 97% and 95%, respectively, between man and monkey. Two monoclonal antibodies (MAbs) directed against an epitope encoded by human exon v5 (VFF8) and an epitope encoded by exon v6 (VFF18) were used to determine expression of CD44 isoforms in man and monkey. Immunohistochemical screening of a representative profile of normal human and cynomolgus tissues revealed that expression of exon v5- and v6-containing CD44 isoforms was almost identical in the two species. Exon v6 staining was observed only in a subset of epithelial tissues, whereas v5 staining was additionally detected on certain non-epithelial tissues. These data suggest that cynomolgus monkey could serve as a system to test the usefulness of antivariant CD44 MAbs with regard to antibody-based tumour therapy.     

PD-L1 is highly expressed in lung lymphoepithelioma-like carcinoma: A potential rationale for immunotherapy

ObjectivesProgrammed cell death-ligand 1 (PD-L1) and driver mutations are found in non-small cell lung cancers (NSCLCs) and may be suitable targets for specific therapies, but their roles in lymphoepithelioma-like carcinoma (LELC) of the lung are unclear.Materials and methodsSixty-six patients with pulmonary LELCs were investigated. Paraffin-embedded tumor sections were stained with PD-L1 antibody. Tumors with moderate-to-strong membrane staining in ≥5% of tumor cells were positive for PD-L1 overexpression. The presence of driver mutations in the genes for epidermal growth factor receptor (EGFR), KRAS, and BRAF were examined by direct sequencing. Anaplastic lymphoma kinase (ALK) and ROS1 levels were determined by immunohistochemistry. Correlations of PD-L1 expression and driver mutations with clinicopathologic parameters were analyzed.ResultsThe overall frequency of PD-L1 overexpression and EGFR mutation was 75.8% and 12.1%, respectively. No KRAS, BRAF, ALK or ROS1 aberrations could be detected. PD-L1 expression was not associated with driver mutations. Multivariate analysis revealed that smoking and advanced stage were independent risk factors for poor overall survival, whereas PD-L1 positivity was not significantly associated with patient outcome.ConclusionThere are high PD-L1 expression and infrequent driver mutations in LELCs compared with conventional NSCLCs. The high expression of PD-L1 in EBV and inflammation associated LELC may provide a rationale for immunotherapy in this subtype of lung cancer.     

胃癌、癌旁粘膜中蛙皮素的免疫组化及图像分析研究

应用免疫组织化学技术对１６１例进展期胃癌行嗜铬粒蛋白Ａ（ＣｇＡ）抗体染色。将检出有ＣｇＡ阳性癌细胞的胃癌７３例，癌旁粘膜６３例行蛙皮素（Ｂｏｍｂｅｓｉｎ，ＢＯＭ）及胃泌素（Ｇａｓｔｒｉｎ，ＧＡＳＴ）抗体染色。应用图像分析系统对癌旁粘膜内分泌细胞进行定量测量。结果显示７３例ＣｇＡ阳性胃癌中１５例ＢＯＭ呈阳性表达，ＢＯＭ阳性胃癌均为低分化胃癌。癌旁胃窦粘膜无萎缩组，ＢＯＭ阳性细胞平均计数较正常对照组明显增多（Ｐ＜００１），且多为弥漫型癌（８５％）。蛙皮素在胃癌及癌旁粘膜中的表达与胃泌素相似。提示蛙皮素有刺激胃癌生长的作用，其作用可能部分是通过刺激胃泌素的释放，部分是直接作用于肿瘤细胞。     

PLC-beta2 is highly expressed in breast cancer and is associated with a poor outcome: a study on tissue microarrays

Despite the identification of many putative biomarkers in breast cancer, a specific pattern of proteins to be used as a prognosticator is not well defined. A growing body of evidence supports the role of phospholipase C (PLC) in the invasion and metastasis of different tumors, including breast cancer. To assess whether the expression of specific PLC isoforms correlates with malignancy-related features of human breast tumors and, hence, could have prognostic significance, an immunohistochemical analysis of PLC-beta2 was performed on tissue microarrays and the relationship between PLC-beta2 expression and biological and clinico-pathological factors was assessed. The analysis of 77 samples of breast tumors with different histotypes revealed that PLC-beta2 is highly expressed in a large majority of the analyzed cancer tissue, particularly ductal and lobular carcinomas, in comparison with normal breast. The expression of PLC-beta2 in primary tumors correlated with size, proliferation index and final grade, while no significant relationship was observed with nodal status or estrogen receptor levels, or with the expression of tumor suppressor p53. Remarkably, high PLC-beta2 levels in primary tumors predict an unfavourable prognosis, suggesting the contribution of this protein to the progression of human mammary carcinomas. Our data indicate that PLC-beta2 expression correlates highly with breast cancer malignancy and suggest that it can be included, as an independent marker, among the prognostic indicators in current use.     

血型抗原Lewis A和Lewis X在甲状腺乳头状癌中的表达

目的 :探讨血型抗原LewisA和LewisX在甲状腺乳头状癌中表达的意义。方法 :采用免疫组织化学EnVision方法 ,测定血型抗原LewisA和LewisX在 70例甲状腺乳头状癌和 70例癌旁正常甲状腺滤泡上皮 ,以及 16例甲状腺滤泡性腺瘤、17例结节性甲状腺肿和 14例桥本氏甲状腺炎中的表达。结果 :LewisA和LewisX在甲状腺乳头状癌中的表达阳性率分别为 94 3% ( 66/ 70 )和 85 7% ( 60 / 70 ) ,癌旁正常甲状腺滤泡上皮中的表达阳性率分别为 2 9% ( 2 / 70 )和 5 7% ( 4 / 70 )。肿瘤直径≥ 1cm组LewisX的表达强度较肿瘤直径 <1cm组明显增高 ,P <0 0 1。淋巴结转移组LewisX的表达强度较非转移组显著增高 ,P <0 0 1。结论 :LewisA和LewisX可作为诊断甲状腺乳头状癌的参考指标。LewisX的表达强度与肿瘤浸润及转移有关