肾癌常见病理类型与CT强化特征的相关性研究

目的:探讨肾癌常见病理类型与CT强化特征的相关性。方法:回顾性分析2010年5月至2015年4月82例肾癌患者,以病理组织为标准,均进行动态增强CT检查,观察不同亚型肾癌CT表现和强化特点情况。结果:透明细胞癌以坏死囊变最明显,占91.49%,和其他病理类型比较差异显著（P<0.05）,嫌色细胞癌在坏死囊变、钙化、均匀上均表现不明显,和透明细胞癌、乳头状癌比较差异显著（P<0.05）;平扫时以透明细胞癌水平最低,而在增强CT皮质期、实质期、排泄期时水平最高,和其他两种比较差异显著（P<0.05）;乳头状癌和透明细胞癌在以上指标上相反,嫌色细胞癌则无明显特异性;肿瘤-皮质增强指数上以透明细胞癌水平最高,以乳头状癌最低,嫌色细胞癌介于两者之间,以上比较差异显著（P均<0.05）。结论:透明细胞癌、乳头状癌、嫌色细胞癌CT强化特征有不同表现。     

乳腺小细胞神经内分泌癌胸壁复发一例

乳腺神经内分泌癌是一种少见的乳腺癌。2003年世界卫生组织（WHO）乳腺及女性生殖器官肿瘤组织分类将乳腺神经内分泌癌正式命名,并按其细胞形态学特点分为实性神经内分泌癌、非典型类癌、小细胞或燕麦细胞癌和大细胞神经内分泌癌四类,其中小细胞癌非常罕见。本文结合本院1例乳腺小细胞神经内分泌癌进行文献复习,探讨其临床病理特点、诊断、鉴别诊断供临床参考。     

肺小细胞癌支气管镜活检的陷阱——附64例免疫组化研究

背景与目的通过支气管镜获得的小细胞肺癌组织,极易造成组织挤压,形态不清,仅凭HE切片进行诊断容易误诊,因此充分应用免疫组化可以进行支气管镜活检小标本的小细胞癌、低分化鳞状细胞癌、非典型类癌、淋巴瘤的诊断和鉴别诊断。方法经支气管镜活检标本,在HE切片染色上诊断为肺癌,倾向小细胞癌的病例64例,进行免疫组化Ki-67、CD56、TTF-1、CgA、Syn、P63、CK5/6、LCA、34βE12的染色。结果64例中小细胞癌61例,非典型类癌2例,低分化鳞状细胞癌1例。结论小细胞癌、低分化鳞状细胞癌、非典型类癌、淋巴瘤在治疗方法不同,充分应用免疫组化可以进行诊断和鉴别诊断,从而可以减少误诊,规避医疗风险。     

肾癌的CT表现及其病理新分型21例分析

[目的]提高基于新病理分型的肾细胞癌的CT诊断认识。[方法]回顾性分析经病理证实的21例肾细胞癌CT表现和病理结果。[结果]11例透明细胞癌,1例颗粒细胞癌,4例混合细胞癌,1例多房囊性肾细胞癌,1例乳头状癌,2例嫌色细胞癌,1例集合管癌。新分型中颗粒细胞癌和多房囊性肾细胞癌均归于透明细胞癌,此型血供丰富,增强扫描后强化明显,不复杂性囊变为其特征;而乳头状癌和嫌色细胞癌相对少血供,易于坏死囊性变,强化程度低于透明细胞癌;集合管癌较少见,CT表现缺乏特异性。[结论]各型肾细胞癌CT表现特异性不强,组织学类型确诊仍依靠病理。了解其CT表现与病理之间的关系有助于CT诊断与鉴别诊断。     

45例原发女性生殖器透明细胞癌临床分析

目的:了解原发女性生殖器透明细胞癌的临床特征、治疗及预后.方法:对我院1962年1月～2000年12月收治的45例原发女性生殖器透明细胞癌患者进行回顾性分析.结果:45例原发女性生殖器透明细胞癌中阴道透明细胞癌3例,宫颈透明细胞癌11例,子宫体透明细胞癌6例,卵巢透明细胞癌25例.平均年龄50岁,其中阴道透明细胞癌患者最小,为33.7岁;宫体透明细胞癌患者最大,为58.3岁.原发女性生殖器透明细胞癌的临床症状与普通腺癌相似,但局部肿瘤较大;以早期肿瘤多见,其中Ⅰ Ⅱ期患者占68.9%,其5年生存率分别为77.3%和77.8%,明显高于Ⅳ期和Ⅳ期患者的5年生存率27.3%和0%(P＜0.01):阴道和卵巢透明细胞癌的5年生存率分别为66.7%和68.0%;明显高于宫颈、宫体透明细胞癌的5年生存率54.6%和16.7%,但统计学检验,均无显著性差异(P＞0.05).结论:原发女性生殖器透明细胞癌早期占多数,分期是影响预后的主要因素,肿瘤易出现腹膜后淋巴结转移和肺转移.     

子宫颈鳞状细胞癌VEGF表达和MVD测定的临床病理意义研究

目的 :探讨血管内皮生长因子 (vas cularendothelialgrowthfactor ,VEGF)表达和微血管密度 (microvesseldensity ,MVD)在子宫颈鳞状细胞癌中的临床病理意义。方法 :应用EnVision二步法检测 92例子宫颈鳞状细胞癌VEGF的表达和MVD。结果 :正常子宫颈鳞状细胞有 2 /10表达VEGF ,92例子宫颈鳞状细胞癌中VEGF表达率为71 7% ( 66/92 ) ,宫颈原位鳞状细胞癌、高、中、低分化鳞状细胞癌VEGF表达分别为6/10、65 0 % ( 13 /2 0 )、75 0 ( 15 /2 0 )、80 0 %( 3 4/4 2 )。且VEGF表达在正常子宫颈鳞状细胞和宫颈原位鳞状细胞癌间差异有统计学意义 ,P =0 0 0 5 7。宫颈原位鳞状细胞癌、高、中、低分化鳞状细胞癌MVD值分别为 2 2 4± 7 9,2 7 9± 9 1,3 0 7± 11 8,3 4 6± 14 3 ,VEGF表达和MVD皆与宫颈鳞状细胞癌的病理分级和临床分期密切相关 ,P<0 0 5。结论 :检测VEGF的表达对宫颈早期鳞状细胞癌的判断可能是有用的指标 ,且对宫颈鳞状细胞癌的病理分级和临床分期具有一定指导意义     

促泌素在小细胞癌中的表达及其临床意义

目的:比较促泌素（secretagogin ，SCGN）与传统神经内分泌标记物在小细胞癌中的表达差异。方法:收集诊断为小细胞癌的标本共39例，其中包括26例小细胞肺癌，13例食管小细胞癌。同时选取肺非典型类癌10例、鳞状细胞癌和腺癌各5 例，食管非典型类癌3 例、鳞状细胞癌和腺癌各5 例作为对照。所有标本均使用SCGN、PGP 9.5、CD56、NSE 、Syn 及CgA 进行SP两步法免疫组织化学染色。结果:97.4%（38/39）小细胞癌表达SCGN，在所有标记中的表达率最高，与NSE 、PGP 9.5 及CgA 比较有显著性差异（P<0.01）；其中SCGN 在肺和食管小细胞癌中的阳性表达率分别为100%（26/26）、92.3%（12/13），两者差异统计学意义（P>0.05）；余标记在肺和食管小细胞癌的表达率也无器官差异性（P>0.05）。 SCGN 在肺和食管非典型类癌中的阳性表达率分别为80.0%（8/10）33.3%（1/3），与相应部位小细胞癌表达率无统计学差异（P>0.05）；余标记在肺非典型类癌与小细胞癌、食管非典型类癌与小细胞癌中的表达率也均无统计差异（P>0.05）。 所有肺和食管的鳞状细胞癌、腺癌均不表达SCGN。结论:SCGN 可作为一种新型的神经内分泌标记物应用于小细胞癌的临床病理诊断，推荐选择SCGN、CD56和Syn 免疫标记组合。同时需要注意的是，SCGN 在肺和食管小细胞癌中的表达无器官差异性，且对小细胞癌与非典型类癌无鉴别诊断价值。      

胃印戒细胞癌临床病理特点的分析

目的：通过对胃印戒细胞癌和非印戒细胞癌患者病例资料的对比,了解胃印戒细胞癌的临床病理特点。方法：回顾性分析2000年1月至2014年12月间第四军医大学附属西京医院经术后病理确诊的5481例胃癌患者的病例资料,根据组织学分型将其分为印戒细胞癌组和非印戒细胞癌组,对两组患者的临床病理资料进行对比分析。结果：印戒细胞癌与非印戒细胞癌在年龄、性别、肿瘤位置及大小、TNM分期、浸润深度、淋巴结转移情况上存在差异（P＜0．05）,在远处转移方面无显著差异（P＞0．05）。早期胃印戒细胞癌的淋巴结转移率高于非印戒细胞癌。结论：胃印戒细胞癌多发生于年轻女性患者,好发部位以胃中下1／3部位多见,早期即可出现较高的淋巴结转移率。     

乳腺印戒细胞癌6例临床病理分析

[目的]探讨乳腺印戒细胞癌的临床病理特征.[方法]收集确诊的6例乳腺印戒细胞癌患者的临床、光镜、免疫组化资料.[结果]患者主要症状为局部肿块,镜下表现为与小叶癌相关和导管癌相关.印戒细胞胞质内黏液AB染色呈蓝色,黏液卡红染色呈红色.免疫组化CK7、GCDFP-15、MG、ER、PR均阳性,CK20为阴性,患者血清巾乳酸脱氢酶未见明显升高,而白细胞介素6和白细胞介素12的含量明显高于正常值.[结论]乳腺印戒细胞癌临床注意与分泌性癌、转移性印戒细胞癌和富于糖原的透明细胞癌进行鉴别.     

肾细胞癌相关分子标志物研究现状及进展

近年,有关肾细胞癌病理学、遗传性及分子生物学方面的研究取得显著进展,这对提高肾细胞癌早期诊断、预后判断及治疗水平有重要意义。目前研究的多个肾细胞癌相关分子标志物(如CAⅨ、B7-H1等)对于肾细胞癌患者的预后判断有一定意义。本文总结了近年来与肾细胞癌患者有关的肿瘤标志物,分析其与肾细胞癌的诊断、治疗和预后方面关系。     

肾癌免疫治疗进展

肾癌细胞特殊的生物学特性使大多数肾癌对化疗和放疗不敏感,随着基因技术、肿瘤免疫、分子生物技术的迅速发展,免疫治疗成为较有前景的一种方法。应用免疫细胞、肿瘤疫苗、免疫基因等方法治疗肾癌已取得了很大的进展。现综述肾癌尤其是晚期肾癌在免疫治疗方面的进展。     

Proliferative activity of intratumoral CD8(+) T-lymphocytes as a prognostic factor in human renal cell carcinoma: clinicopathologic demonstration of antitumor immunity.

Tumor-infiltrating lymphocytes, particularly CD8(+) T cells, could be a manifestation of antitumor immunity. We clinicopathologically analyzed the biological significance of tumor-infiltrating lymphocytes in 221 patients with renal cell carcinoma without preoperative treatments. More abundant infiltration of tumor tissue not only by CD8(+) but also CD4(+) T cells was associated with shorter survival of the patients, because of the positive correlation between the number of lymphocytes and representative tumor grade factors. This suggests that immune cell reactions are more pronounced as the tumor grade/biological malignancy progresses, probably because of increased antigenicity of tumor cells. We next analyzed the proliferative activity of CD8(+) T cells that infiltrated in tumor cell nests, which could also reflect antitumor immunity. Higher labeling index of Ki-67, a proliferation-associated antigen, among CD8(+) T cells in contact to tumor cells was associated with a longer survival by both uni- and multivariate analyses. Our data in human renal cell carcinoma suggest that infiltration of tumor tissue by T cells itself does not denote the efficacy of antitumor immunity because of its dependence on the biological malignancy of tumor cells, but infiltration of tumor tissue by CD8(+) T cells bearing more pronounced proliferative activity could reflect effective antitumor immunity. This concept would be important for future immunotherapy of human cancer.     

The role of vascular cell adhesion molecule-1 in tumor immune evasion

Tumor immune escape is a critical trait of cancer but the mechanisms involved have yet to fully emerge. One recent study has shown that tumor cells can escape T-cell immunity by overexpressing the endothelial cell adhesion molecule vascular cell adhesion molecule-1 (VCAM-1), which normally mediates leukocyte extravasion to sites of tissue inflammation. Renal cell carcinoma (RCC) was identified as one tumor type where VCAM-1 is commonly highly overexpressed. Together, our findings suggest that RCCs might exploit VCAM-1 overexpression for immune escape.     

Chemokines as therapeutic targets in renal cell carcinoma

Targeting novel pathways associated with tumor angiogenesis, invasion and immunity, may lead to improvement in patient outcomes for renal cell carcinoma. Chemokines potentiate tumor growth, metastasis, angiogenesis and immune evasion through interactions with stromal cells and neoplastic cells. Further understanding of the mechanisms involved in chemokine-mediated angiogenesis and metastasis may lead to improved therapeutic strategies in this disease. Interactions between chemokine expression and signaling, and the VEGF and hypoxia-inducible factor pathways offer important opportunities to intervene in the process of renal cell carcinoma proliferation, angiogenesis and invasion. Modulation of the CXCR3/CXCR3-ligand or the CXCR4/CXCL12 biologic axis may be potential therapeutic targets for the treatment of renal cell carcinoma. Furthermore, combination treatment with agents targeting chemokine signaling with therapies directed at angiogenesis and tumor immunity may lead to improved outcomes in this disease.     

AIM2在肿瘤中的研究进展

黑色素瘤缺乏因子(Absent in melanoma 2,AIM2),作为一种细胞内DNA感受器,能够感受到DNA病毒或细菌感染时释放到细胞浆的dsDNA,经ASC产生炎症复合体,进而活化Caspase-1,引起炎症因子IL-1β和IL-18的成熟和分泌,或引起Pyroptosis样细胞死亡,因此AIM2在固有免疫应答中发挥重要作用。近年的研究显示,AIM2能影响肿瘤的发生与发展,在肝癌、乳腺癌中表现为抑癌因子,抑制肿瘤的进展;在宫颈癌、口腔鳞状细胞癌中却表现出致癌效应,促进肿瘤的发展。这些研究结果对恶性肿瘤的诊断及预后起到帮助作用。     

CD+4CD+25调节性T细胞与肿瘤免疫

 近期研究发现一个有独特免疫调节功能的T细胞亚群：CD+4 CD+25调节性T细胞,不仅能抑制自身免疫性疾病发生,还参与肿瘤免疫的调节。这群细胞具有免疫无能和免疫抑制特性,与肿瘤免疫逃逸有密切的关系。肿瘤环境中CD+4 CD+25调节性T细胞增加,导致肿瘤免疫失调,去除这群细胞可有效诱导肿瘤免疫,为肿瘤治疗提供了一种新的思路。     

Nano‐pulse stimulation induces potent immune responses,eradicating local breast cancer while reducing distant metastases

Nano‐pulse stimulation (NPS) as a developing technology has been studied for minimally invasive, nonthermal local cancer elimination for more than a decade. Here we show that a single NPS treatment results in complete regression of the poorly immunogenic, metastatic 4T1‐Luc mouse mammary carcinoma. Impressively, spontaneous distant organ metastases were largely prevented, even in those animals with incomplete tumor regression. All tumor‐free mice were protected from secondary tumor cell challenge, demonstrating a vaccine‐like effect. NPS treatment induced antitumor immunity, long‐term memory T cells, destruction of tumor microenvironment and reversal of the massive increase of immune suppressor cells in the tumor microenvironment and blood. NPS‐treated 4T1 cells exhibited release of damage‐associated molecular patterns (DAMPs), including calreticulin, HMGB1 and ATP, and activated dendritic cells. Those findings suggest that NPS is a potent immunogenic cell death inducer that elicits antitumor immunity to prevent distant metastases in addition to local tumor eradication.     

An Immunogram for the Cancer-Immunity Cycle: Towards Personalized Immunotherapy of Lung Cancer

IntroductionThe interaction of immune cells and cancer cells shapes the immunosuppressive tumor microenvironment. For successful cancer immunotherapy, comprehensive knowledge of antitumor immunity as a dynamic spatiotemporal process is required for each individual patient. To this end, we developed an immunogram for the cancer-immunity cycle by using next-generation sequencing.MethodsWhole exome sequencing and RNA sequencing were performed in 20 patients with NSCLC (12 with adenocarcinoma, seven with squamous cell carcinoma, and one with large cell neuroendocrine carcinoma). Mutated neoantigens and cancer germline antigens expressed in the tumor were assessed for predicted binding to patients’ human leukocyte antigen molecules. The expression of genes related to cancer immunity was assessed and normalized to construct a radar chart composed of eight axes reflecting seven steps in the cancer-immunity cycle.ResultsThree immunogram patterns were observed in patients with lung cancer: T-cell–rich, T-cell–poor, and intermediate. The T-cell–rich pattern was characterized by gene signatures of abundant T cells, regulatory T cells, myeloid-derived suppressor cells, checkpoint molecules, and immune-inhibitory molecules in the tumor, suggesting the presence of antitumor immunity dampened by an immunosuppressive microenvironment. The T-cell–poor phenotype reflected lack of antitumor immunity, inadequate dendritic cell activation, and insufficient antigen presentation in the tumor. Immunograms for both the patients with adenocarcinoma and the patients with nonadenocarcinoma tumors included both T-cell–rich and T-cell–poor phenotypes, suggesting that histologic type does not necessarily reflect the cancer immunity status of the tumor.ConclusionsThe patient-specific landscape of the tumor microenvironment can be appreciated by using immunograms as integrated biomarkers, which may thus become a valuable resource for optimal personalized immunotherapy.     

基于TCGA数据库免疫基因表达谱构建253例宫颈鳞状细胞癌免疫亚组

目的采用美国肿瘤基因组图谱(TCGA)数据库免疫基因表达谱构建宫颈鳞状细胞癌免疫亚型,并分析各免疫亚组特征,为宫颈鳞状细胞癌预后分析及治疗提供新指标。方法 TCGA数据库共下载253例宫颈鳞状细胞癌及3例癌旁正常组织的mRNA表达谱及临床数据。根据单样本基因集富集分析(ssGSEA)得分情况,将宫颈鳞状细胞癌分为高免疫组、中等免疫组及低免疫组3个免疫亚组。采用Kolmogorov-Smirnov检验分析各免疫亚组肿瘤微环境和免疫细胞亚群比例,运用单因素方差分析比较各组人类白细胞抗原(HLA)相关基因及程序性死亡配体1(PD-L1)基因表达情况,采用Log-rank检验及多因素Cox回归分析进行生存分析。对免疫亚组做基因富集分析,确定基因本体论(GO)及京都基因与基因组百科全书(KEGG)通路富集区域。结果 3个免疫亚组免疫评分(χ²=144.87)、基质评分(χ²=116.127)、总评分(χ²=37.941)及肿瘤纯净度(χ²=116.127)比较差异均有统计学意义,均P<0.001。高免疫组19个HLA相关基因表达高于中等免疫组及低免疫组,均P<0.001。PD-L1基因表达及CD8+T细胞比例在3个免疫亚组之间差异有统计学意义(F=39.048,P<0.001;χ²=46.654,P<0.001)。3个免疫亚组5年生存率差异有统计学意义,χ²=6.400,P=0.029。免疫分组是影响宫颈鳞状细胞癌患者预后的主要因素,P<0.05。高免疫组GO生物学过程富集区域及KEGG通路主要集中于免疫相关信号通路。低免疫组GO生物学过程富集区域和KEGG通路主要集中于癌症相关信号通路。结论基于TCGA数据库免疫基因表达谱将宫颈鳞状细胞癌分为3种免疫亚组,不同亚组具有不同的分子特征和临床预后,对分析宫颈鳞状细胞癌预后、指导宫颈鳞状细胞癌治疗具有临床意义。     

Clinical significance of MHC class II-associated invariant chain expression in human gastric carcinoma

MHC class II antigens serve as restricted elements for cell presenting antigens to CD4+ helper T cells. CD4+ T cells and CD8+ cytotoxic T cells, which are tumor-infiltrating lymphocytes (TILs), and play a major role in the survey and attack against tumor cells in primary lesions. Invariant chain (Ii) has several functions in MHC class II-restricted antigen presentation. In addition, Ii is found to be closely involved in the regulation of anti-tumor immunity in several tumor types. However, the significance of Ii expression in tumor cells is not fully illustrated. Immunohistochemical staining of Ii expression was performed in 58 cases of human gastric carcinoma specimens. The prognostic analysis of patients with gastric carcinoma was also performed. A total of 67.2% (39/58) gastric carcinomas were found to be Ii-positive, whereas only 20.7% (12/58) showed positive immunoreactivity with anti-MHC class II determinants. Furthermore, Ii expression showed significant correlation with the differentiation of gastric carcinoma (p<0.05). Ii expression also showed an inverse correlation with the frequency of TILs around carcinoma tissues, as well as with the prognosis of gastric carcinoma (p<0.01). Ii expression is closely correlated with anti-tumor immunity in human gastric carcinoma. Therefore, Ii may serve as an independent clinical marker for poor biological behavior and prognostic analysis in patients with gastric carcinoma.