219例弥漫性大B细胞淋巴瘤免疫表型及遗传学特征分析

  目的  探讨国内弥漫性大B细胞淋巴瘤（DLBCL）免疫表型分型及BCL-2和BCL-6基因异常的分布情况。  方法  应用组织芯片和免疫组织化学法及FISH技术对219例DLBCL的免疫表型及BCL-2和BCL-6基因异常进行检测,根据Hans法进行分型;并收集国内7家相关研究报道,进行综合分析。  结果  本组研究结果:219例DLBCL中,非GCB型（165例,75.3%）显著高于GCB型（54例,24.7%）（P < 0.001）。BCL-2基因异常共49例（25.8%）,其中t （14;18）5例（2.6%）均为GCB型;BCL-2基因扩增44例（23.2%）,GCB型4例（8.5%）,非GCB型40例（28.0%）,有显著性差异（P=0.013）。BCL-6基因重排共42例（22.1%）,GCB型7例（14.9%）,非GCB型35例（24.5%）,差异无统计学意义（P=0.189）。BCL-2基因扩增和BCL-6基因重排呈显著负相关（r=-0.180,P=0.013）。8组综合分析:1 259例中非GCB型（879例,69.8%）明显高于GCB型（380例,30.2%）（P < 0.001）;免疫表型中CD10和MUM1阳性率组间差异较小（P=0.047和P=0.048）,而BCL-6及BCL-2阳性率组间存在明显差异（P < 0.001）。  结论  我国DLBCL患者在主要免疫表型和遗传学特征方面具有独特性,对此值得进行深入研究。      

乳腺包被性乳头状癌的临床病理分析

目的 探讨乳腺包被性乳头状癌（encapsulated papillary carcinoma, EPC）的临床病理学特征、诊断、治疗及预后。方法 回顾性分析新疆医科大学附属肿瘤医院病理科2010年1月-2013年12月间,诊断为囊内乳头状癌或包被性/包裹性乳头状癌35例及48例对照组导管内乳头状癌的临床病理资料及免疫表型。结果 EPC患者均为女性,年龄29~83岁,平均61岁,肿块大小平均2.4 cm (范围0.6~4 cm)。35例EPC中,22例为单纯性EPC、7例伴导管原位癌、4例伴微小浸润癌、2例伴非特殊类型浸润癌。35例EPC与48例导管内乳头状癌病变内部均未见肌上皮细胞,CK5/6及p63肌上皮染色结果显示,EPC病变周围肌上皮数量较导管内乳头状癌导管壁肌上皮数量明显减少,差异具有统计学意义（P<0.05）;35例EPC中80%激素受体阳性,5.71%HER2表达阳性。8例（22.86%）EPC患者行肿块切除,27例（77.14%）患者行乳房切除术,3例（8.57%）发生淋巴结转移。术后经随访2~48月,患者均存活。结论 乳腺包被性乳头状癌是一种好发于老年女性的恶性肿瘤,病变周缘肌上皮明显减少甚至缺如,单纯性EPC也可发生淋巴结转移,被认为是一种惰性的浸润癌,生物学行为介于原位癌与浸润癌之间。若单独发生或伴随原位癌及微小浸润癌时,应参照原位癌治疗, EPC伴随浸润癌时,应参照浸润癌的治疗标准进行。     

乳头状肾细胞癌4例报道及文献复习

目的:探讨乳头状肾细胞癌(PRCC)的临床和病理特征。方法:对4例乳头状肾细胞癌临床表现、病理特征及免疫组化表型进行观察分析并文献复习。结果:肿瘤组织呈乳头状或管状结构排列,乳头中心及间质内有泡沫细胞浸润,有明显出血坏死。结论:乳头状肾细胞癌诊断依赖病理特征及免疫表型,并需与其他有乳头状结构的肾恶性肿瘤进行鉴别。     

套细胞淋巴瘤23例临床特征及免疫表型分析

 目的　探讨套细胞淋巴瘤的临床特征和免疫表型特点。方法　回顾性分析23例套细胞淋巴瘤患者的临床资料。对患者的年龄、性别、临床分期、淋巴结及结外病变、骨髓活检、血清乳酸脱氢酶和免疫表型等进行分析。结果　患者中位年龄62岁（44～74岁）,≥60岁者15例（65.2 %）。男女比例为4.8∶1。Ann Arbor临床分期Ⅲ期12例,Ⅳ期9例。首发症状为浅表淋巴结肿大20例（87.0 %）,以颈部最多;伴有腹腔内淋巴结肿大13例（56.5 %）。病程早期发热者9例（39.1 %）,15例行骨髓穿刺患者中骨髓有肿瘤细胞浸润10例（66.6 %）。血清乳酸脱氢酶增高11例（47.8 %）。免疫表型CD5阳性14例（60.9 %）,CD20阳性21例（91.3 %）。CyclinD1过度表达19例（82.6 %）。结论　套细胞淋巴瘤主要发生在男性老年人群,初诊时多为晚期,多有骨髓浸润。首发症状为浅表淋巴结肿大,结外病变明显。免疫表型检测显示套细胞淋巴瘤有成熟B细胞（CD+20）抗原,同时兼有T细胞（CD+5）的抗原。免疫组织化学呈现CyclinD1过度表达可为诊断套细胞淋巴瘤的金标准。     

132例初发儿童急性淋巴细胞白血病免疫表型及细胞遗传学特征分析

目的：探讨儿童急性淋巴细胞白血病（ALL）的免疫表型及细胞遗传学特征,为其诊断及治疗提供依据。方法：采用多参数流式细胞术（FCM）对132例初发儿童 ALL 患者进行免疫表型分析,并应用荧光原位杂交（FISH）技术检测其细胞遗传学特点。结果：132例 ALL 患者中,12.9%（17/132）为 T 淋巴细胞急性淋巴细胞白血病（T - ALL）,87.1%（115/132）为 B 淋巴细胞急性淋巴细胞白血病（B - ALL）。46.2%（56/132）的ALL 患者表达髓系抗原,CD13是 ALL 中最常见的髓系抗原,其阳性率为28.0%。T - ALL 髓系相关抗原表达阳性率为47.1%,与 B - ALL 的46.1%比较,差异无统计学意义（χ2=0.006,P =0.940）。可供核型分析的96例 ALL 中,核型异常者50例（52.1%）,其中染色体数目异常26例,染色体结构异常24例。96例 ALL 患者中,TEL/ AML1融合基因阳性21例（21.8%）,BCR/ ABL 融合基因阳性14例（14.6%）,TCF3/ PBX1融合基因阳性5例（5.2%）,MLL 重排3例（3.1%）。对不同免疫分型患者细胞遗传学异常检出率进行比较,差异均无统计学意义（P >0.05）。结论：儿童 ALL 免疫表型和细胞遗传学具有一定的特点,两者联合检测对 ALL 的诊断及分型具有重要的价值。     

结直肠癌组织中ARID1A基因突变和MSH2蛋白表达与临床病理特征及预后的相关性

目的:检测结直肠癌（CRC）组织中富含AT结合域1A（ARID1A）基因突变和 mutS同种组织蛋白2(MSH2)蛋白表达,分析两者的临床意义。方法:选取自2017年1月至2018年1月期间我院诊治的142例CRC患者作为研究对象。采用直接测序法检测CRC癌组织中ARID1A基因突变。免疫组化检测癌及癌旁组织MSH2蛋白表达。Spearman秩相关分析ARID1A基因突变和MSH2蛋白表达的相关性。统计学分析ARID1A基因突变、MSH2蛋白表达与CRC临床病理特征的关系。Kaplan-Meier生存分析ARID1A基因突变和MSH2蛋白表达对患者生存预后的影响。单因素及多因素Cox回归分析影响CRC患者生存预后的因素。结果:142例CRC癌组织中,27例发生ARID1A基因突变,ARID1A基因突变率为19.01%（27/142）。MSH2棕黄色阳性表达主要位于细胞核。CRC癌组织中MSH2阳性率为51.41%（73/142）,明显低于癌旁组织91.55%（130/142）（χ2=56.116,P=0.000）。不同肿瘤TNM分期、淋巴结转移CRC癌组织中ARID1A基因突变、MSH2阳性率差异具有统计学意义（P＜0.05）。CRC癌组织中ARID1A基因突变和MSH2表达呈显著负相关性(r=-0.575,P=0.000)。ARID1A基因突变组患者3年总体生存率为37.04%（10/27）,明显低于野生型组患者67.27%（74/110）（P=0.000）;MSH2阳性表达组患者3年总体生存率为81.43%（57/70）,明显高于阴性表达组患者42.30%（27/67）（P=0.000）。ARID1A基因突变型、MSH2阴性表达、肿瘤TNM分期Ⅲ期及伴淋巴结转移是影响CRC患者预后的独立危险因素（P＜0.05）。结论:ARID1A基因、MSH2表达与CRC患者肿瘤分期及淋巴结转移有关,是CRC患者预后预测的独立因素。     

非霍奇金B细胞淋巴瘤150例临床病理分析

 目的 探讨非霍奇金B细胞淋巴瘤（B-NHL）的病理形态和免疫表型在B-NHL诊断的价值,分析B-NHL的临床意义。方法 应用HE 和免疫组织化学（LSAB法）对150例B-NHL重新诊断分类。结果 150例B-NHL中最常见是弥漫大B细胞淋巴瘤（77例 ,51.3 %）,其次是黏膜相关淋巴组织结外边缘区细胞淋巴瘤（23例 15.3 %）。发生于淋巴结者占40.6 %（61例）,结外为54.9 %（83例）。单纯HE形态诊断对比形态结合免疫表型的诊断结果,符合率达80 %,免疫组织化学可将B-NHL的诊断正确率提高近20 %（P＜0.01）。结论 病理形态是淋巴瘤诊断的基础,免疫表型在诊断和分型中具有重要作用,二者与临床特征结合可使绝大多数淋巴瘤得到明确诊断。     

弥漫性大B细胞淋巴瘤临床病理分析

 目的　探讨弥漫性大 B细胞淋巴瘤（DLBCL）的临床病理特征、免疫表型,以提高对DLBCL的诊断水平。方法　对22例DLBCL患者进行回顾性分析,复习组织形态和临床表现,补充完善所有患者CD20、CD3、CD10、bcl-6、MUM-1、Ki-67免疫表型测定,为与其他肿瘤相鉴别,对精原细胞瘤、间变性大细胞性淋巴瘤、母细胞型套细胞淋巴瘤部分病例检测AE1／3、PLAP、CD30、ALK、CD5和CyclinD1。结果　22 例患者均为原发DLBCL,男性14例,女性8例,年龄21～71岁,平均48岁;13例结内,9例结外。生发中心细胞（CGB）型13 例（结内7例,结外6例）,非CGB（non-CGB）型9例（结内6例,结外3例）,结合临床和组织形态学17例可诊断,再结合免疫组织化学22例均可诊断。结论　DLBCL形态学、免疫表型及临床表现有一定的特征性,三者相结合能较准确诊断。     

乳腺导管内乳头状瘤的临床病理及预后分析

目的 乳腺导管内乳头状瘤是发生在乳头乳晕区的乳腺良性肿瘤,临床上较为常见.本研究探讨乳腺导管内乳头状瘤临床病理特征与复发的关系.方法 回顾性分析2010-01-01-2015-07 01中国医学科学院肿瘤医院547例乳腺导管内乳头状瘤患者的临床病理资料.结果 547例患者中,348例不伴有非典型增生(63.6％),199例(36.4％)伴有非典型增生.中位随访37个月,导管内乳头状瘤组和导管内乳头状瘤伴非典型增生组3年无复发生存率分别为98.2％和95.0％;3年无肿瘤生存率分别为99.1％和98.5％.2组无复发生存曲线比较差异有统计学意义,P=0.009.Cox分析结果显示,非典型增生是影响术后复发的主要因素,RR=0.183,95％CI=0.045～0.675,P-0.011;Logistic回归分析结果显示,伴有乳房肿物(OR=0.448,95％CI=0.29～0.68,P＜0.001)、外周型导管内乳头状瘤(OR=0.444,95％CI=0.45～0.72,P=0.001)术后病理更易出现非典型增生.结论 非典型增生情况是乳腺导管内乳头状瘤术后复发重要预测指标.     

CD103+CD8+T细胞在结直肠癌组织中的浸润分布及其临床意义

[摘要] 目的:研究组织驻留CD8+T细胞（CD103+CD8+T细胞）在结直肠癌（colorectal cancer,CRC）组织中浸润程度及分布特征,分析其浸润程度与患者临床病理特征及预后的关系。方法:选用上海芯超生物科技有限公司的88 例结肠癌HColA180Su14和77 例直肠癌HRec-Ade180Sur-03 组织芯片,应用免疫荧光染色法分别检测CRC组织及相应癌旁组织中CD103+CD8+T细胞的浸润分布特征及程度,Wilcoxon 秩和检验比较CRC及癌旁组织中CD103+CD8+T细胞浸润程度,χ2检验分析CRC中CD103+CD8+T细胞浸润程度与患者临床病理特征的关系;Kaplan-Meier 生存分析CD103+CD8+T细胞浸润程度与患者预后的关系,拟合Cox 模型评价不同指标与患者预后的关系。结果: CRC组织中CD103+CD8+T 细胞浸润程度与癌旁组织比较差异无统计学意义（P>0.05）,有远处转移患者中CD103+CD8+T细胞高度浸润的比率显著低于无远处转移患者（P<0.01）,CD103+CD8+T细胞浸润程度与患者其他临床病理特征无明显相关（P>0.05）。Kaplan-Meier生存分析显示,CD103+CD8+T细胞高度浸润患者的OS较低度浸润患者显著延长（54.42% vs 25.00%,P<0.05）,多因素Cox 显示,病理分级（P<0.01）和CD103+CD8+T细胞高度浸润（P<0.05）均可作为CRC患者预后的独立影响因素。结论: CRC组织中CD103+CD8+T细胞浸润与预后相关,提示其在CRC发生发展过程中发挥重要作用。     

肝癌衍生生长因子在Ⅰ期非小细胞肺癌中的表达及其临床意义

目的探讨肝癌衍生生长因子(HDGF)在Ⅰ期非小细胞肺癌(NSCLC)中的表达及其临床意义,以及可能的作用机制。方法应用免疫组化SP法检测118例Ⅰ期NSCLC和30例正常肺组织中HDGF的表达,同时检测VEGF的表达以及Ki-67抗原标记率。结果HDGF在肺癌组织中表达普遍上调,正常肺组织HDGF评分为52.23±10.35,肺癌组织评分为156.73±70.95,差异有统计学意义(P<0.01);HDGF表达与病理类型显著相关,腺癌的HDGF评分明显高于鳞癌,差异有统计学意义(P=0.001),而与其他临床病理因素均无明显相关性。肺癌组织中HDGF评分随着VEGF表达强度的增强而升高,VEGF低表达组的HDGF评分为142.81±59.84,高表达组为171.77±81.07,差异有统计学意义(P=0.028);肺癌组织中Ki-67抗原标记率随着HDGF表达的增加而升高,HDGF低表达组的Ki-67抗原标记率为17.80%±5.63%,HDGF高表达组的Ki-67抗原标记率为30.49%±7.88%,差异有统计学意义(P=0.001)。单因素生存分析表明,HDGF高表达组的5年生存率(40.0%)较低表达组(77.5%)明显降低,差异有统计学意义(P=0.008)。多因素生存分析结果表明,HDGF为Ⅰ期NSCLC的独立预后指标(RR=1.011,P=0.002)。结论HDGF在Ⅰ期NSCLC中的表达普遍上调,可以作为Ⅰ期NSCLC的独立预后指标。HDGF可能通过促进细胞增殖和新生血管生成在Ⅰ期NSCLC的发生发展中起到重要的作用。     

Expression of hepatoma-derived growth factor is correlated with lymph node metastasis and prognosis of gastric carcinoma.

PURPOSE: Hepatoma-derived growth factor (HDGF) is a unique nuclear/growth factor and might play an important role in the development and progression of carcinomas. In the present study, association of HDGF expression with recurrence and prognosis of gastric carcinoma was examined. PATIENTS AND METHODS: HDGF expression in 317 patients with gastric carcinoma (233 males and 84 females) with ages ranging from 26 to 81 years (median, 60 years) was analyzed by immunohistochemistry. Samples with >90% of tumor cells to express positive immunoreactivity similar to or stronger than that in endothelial cells both for nucleus and cytoplasm were regarded as HDGF index level 2, and others as HDGF index level 1. RESULTS: One hundred and eighty-two cases showed level 1 HDGF expression, whereas 135 cases showed level 2 HDGF expression. Patients with level 2 expression showed higher rates of proximal tumor location (P < 0.0001), large tumor size (P < 0.0001), infiltrative tumor growth (P < 0.0001), presence of vascular and lymphatic invasion (P < 0.0001 for both), presence of lymph node metastasis (P < 0.0001), deep tumor invasion (P < 0.0001), and poorer disease-free and overall survival (P < 0.0001 for both) compared to those with level 1 expression. Multivariate analysis revealed HDGF expression level as an independent prognosticator for disease-free and overall survival. CONCLUSION: HDGF expression level was shown to be a prognostic factor for gastric carcinoma.     

Quantitative expression of protein markers of plasminogen activation system in prognosis of colorectal cancer

BACKGROUND AND OBJECTIVES: Certain pathophysiological markers may be helpful in selecting further therapies for patients with resected colorectal cancer (CRC). The aim of this study was to determine whether expression of proteins of the plasminogen activation system (PAS), which are important in tumor spread and growth, can predict outcome of human CRC. METHODS: Protein expression of the PAS, including urokinase-type plasminogen activator (uPA) and its receptor (uPAR), plasminogen (Plg), and plasminogen activator inhibitors-1 and -2 (PAI-1 and PAI-2), was determined in the colonic tissue samples of 56 patients with resected primary CRC by quantitative immunohistochemistry and correlated with clinicopathological parameters and patient outcome. RESULTS: Overexpression of uPA (t-test, P < 0.001), uPAR (P < 0.001) and PAI-1 (P = 0.031) was significantly associated with liver metastatic CRC tumors. Higher uPA or uPAR expression level was significantly correlated with overall survival (OS; log-rank, P = 0.001 and P < 0.0001) and cancer-specific survival (CSS; P = 0.001 and P < 0.0001) after the first CRC resection. The predictive value of both uPA and uPAR in liver metastasis, OS and CSS was independent from other parameters (multivariate Cox regression: all P < 0.001). CONCLUSIONS: uPA and uPAR may be independent predictors of liver metastasis, patient overall survival and cancer-specific survival after resection of colorectal tumors.     

Node-negative colorectal cancer at high risk of distant metastasis identified by combined analysis of lymph node status, vascular invasion, and Raf-1 kinase inhibitor protein expression.

PURPOSE: To identify independent clinicopathologic factors and protein markers leading to the identification of colorectal cancer (CRC) patients with mismatch repair proficiency at risk of developing metastasis and, consequently, more likely to benefit from combined modality therapy. EXPERIMENTAL DESIGN: Immunohistochemistry for 22 tumor markers was done using a tissue microarray. A subset of 387 CRC patients with complete clinicopathologic data and TNM stage was analyzed. Univariate and multivariate analyses were done to identify independent predictive markers of metastasis. The results were validated on 810 CRC patients. RESULTS: In univariate analysis, T stage (P < 0.001), N stage (P < 0.001), tumor grade (P = 0.005), vascular invasion (P < 0.001), tumor budding (P < 0.001), positive expression of beta-catenin (P = 0.015), overexpression of RHAMM (P = 0.008), negative expression of Raf-1 kinase inhibitor protein (RKIP; P = 0.001), and absence of intraepithelial lymphocytes (P = 0.017) were significantly associated with the presence of distant metastasis. In multivariate analysis, higher N stage (P < 0.001), presence of vascular invasion (P = 0.009), and RKIP loss (P = 0.003) independently predicted distant metastatic disease. A subgroup of node-negative patients was identified as high risk for distant metastasis and showed a similar probability of metastatic risk and nearly identical survival times as node-positive patients with absence of vascular invasion and positive RKIP expression (metastatic risk, 24% and 22%; median survival time, 45.0 and 47.0 months, respectively). CONCLUSION: The combined analysis of N stage, vascular invasion, and RKIP expression is highly predictive of distant metastasis in patients with mismatch repair--proficient CRC. Additionally, a subgroup of more aggressive N(0) tumors can be identified by evaluating vascular invasion and RKIP expression.     

UHRF1蛋白在结直肠癌中的表达情况及其预后判断价值

目的：探讨泛素样含PHD和环指域1(UHRF1)蛋白在结直肠癌中的表达及其预后判断价值。方法：采用组织微阵列联合免疫组织化学(TMA-IHC)技术检测201例结直肠癌中UHRF1蛋白的表达情况,分析其与临床病理指标及术后生存时间之间的相关性。结果：UHRF1蛋白在结直肠癌组织中的表达阳性率为54.2%(109/201),显著高于配对的手术切端形态学正常的组织(P<0.01)。Kaplan-Meier生存分析显示,UHRF1蛋白表达阳性患者术后生存时间短于表达阴性的患者(P=0.023)。Cox回归分析结果表明,UHRF1蛋白是结直肠癌患者根治术后的一个独立预后因素(P=0.008)。结论：UHRF1蛋白可能作为结直肠癌患者术后预后判断的分子标志。     

Mucinous histology predicts for reduced fluorouracil responsiveness and survival in advanced colorectal cancer.

BACKGROUND: Mucinous carcinoma of the colon and rectum (mucinous CRC) is a histological subtype of colorectal adenocarcinoma for which there is little data on chemotherapy responsiveness. The purpose of this study was to investigate specifically the efficacy of fluorouracil-based first-line chemotherapy in patients with advanced mucinous CRC. PATIENTS AND METHODS: All patients with advanced mucinous CRC enrolled in three prospective randomized trials evaluating infused 5-fluorouracil as first-line treatment were compared with patients with non-mucinous subtypes enrolled in the same trials in a case-control study. Prognostic factors associated with overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were identified using univariate and multivariate logistic and/or Cox proportional hazards analyses. RESULTS: The study included 135 patients (45 cases and 90 controls). The response rates for cases and controls were 22% [95% confidence interval (CI), 11% to 38%] and 47% (95% CI, 36.1% to 58.2%), respectively (P=0.0058). Median OS for the mucinous CRC patients was 11.8 months (95% CI, 8.87-14.8) compared with 17.9 months (95% CI, 13.38-22.39) in the control group (univariate analysis, P=0.056); after correcting for significant prognostic factors by multivariate Cox regression analysis, P=0.0372 and hazard ratio (HR)=1.497 (1.02-2.19). CONCLUSION: Patients with advanced mucinous CRC have a poorer response to fluorouracil-based first-line chemotherapy and reduced survival compared with patients with non-mucinous CRC.     

The expression and prognostic significance of hepatoma-derived growth factor in oral cancer

Hepatoma-derived growth factor (HDGF) participates in oncogenic progression and represents a prognostic factor in several types of cancer. This study aimed to elucidate the role of HDGF during oral carcinogenesis. HDGF expression and the tumorigenic behaviors in human oral cell lines were investigated by immunoblotting, invasion and colony formation assays. Recombinant adenovirus vectors were employed to modulate the HDGF level in oral cancer cells. Immunohistochemical analysis using tissue microarray (TMA) consisting of surgically resected samples from 95 oral cancer patients was performed to delineate the correlation between HDGF expression and clinic-pathological parameters. HDGF expression was higher in malignant oral cancer cells than benign ones. Adenovirus-mediated HDGF overexpression and knockdown demonstrated the cellular HDGF level regulated the tumorigenic behaviors of oral cancer cells. Immunohistochemical analysis revealed increased HDGF expression in the nucleus and cytoplasm in oral cancer tissues. The nuclear HDGF expression was significantly correlated with tumor stage (P=0.004) and grade (P=0.013) while the cytoplasmic HDGF expression was associated with tumor necrosis (P=0.002). Kaplan-Meier analysis revealed that patients with high nuclear HDGF expression had significantly worse 5-year disease-specific survival (P=0.0069), metastasis-free survival (P=0.0168), and local recurrence-free survival (P=0.0047). Multivariate analysis indicated that the nuclear HDGF labeling index was an independent prognostic factor for disease-specific and local recurrence-free survival. HDGF overexpression contributes to the oncogenic processes in oral cancer cells and constitutes a novel prognostic factor for survival outcome of oral cancer patients.