头颈部鳞状细胞癌肿瘤微环境的研究进展

肿瘤微环境在头颈部鳞状细胞癌(head and neck squamous cell carcinoma, HNSCC)等多种癌症中已得到广泛研究,其各组成部分对肿瘤的预后有重要指示意义,并直接指导肿瘤的治疗策略。该文综述了HNSCC微环境中各组成成分与肿瘤的相互作用关系,包括免疫细胞如中性粒细胞、巨噬细胞及T细胞,以及免疫检查点PD-1/PD-L1。     

头颈部鳞状细胞癌预后相关的miRNAs的生物信息学分析

目的 利用癌症基因组图谱（TCGA）数据库微小核糖核酸（miRNAs）表达谱数据分析头颈部鳞状细胞癌（HNSCC）与癌旁正常组织间差异表达的miRNAs,结合临床信息寻找与HNSCC预后相关的miRNAs。方法 从TCGA中下载miRNAs表达数据,包括39例HNSCC患者和39个肿瘤邻近正常组织样本筛选差异表达的miRNAs,应用481例HNSCC患者的miRNAs表达谱和临床信息来评估找到的差异表达miRNAs的预后作用。结果 共筛选出114个差异表达的miRNAs,包括60个上调和54个下调的miRNAs。Kaplan-Meier生存分析显示miR-4652-5p和miR-99a-3p与HNSCC患者预后相关,单因素和多因素Cox回归分析显示,miR-4652-5p和miR-99a-3p是HNSCC的重要预后因素。结论 miR-4652-5p和miR-99a-3p与HNSCC患者预后相关,但miR-4652-5p和miR-99a-3p在头颈鳞状细胞癌发生发展中的分子机制仍需更全面的基础和临床研究进行探讨。     

头颈部鳞状细胞癌巨噬细胞关键基因的筛选分析

目的 应用生物信息学的方法分析筛选头颈部鳞状细胞癌(HNSCC)巨噬细胞中的潜在关键基因,为HNSCC的预后提供靶点。方法 基于在线数据库,利用一致流形近似与投影(UMAP)降维,捕获巨噬细胞群;进一步通过t-分布随机近邻嵌入(tSNE)聚类降维分析肿瘤组织与正常组织细胞群分布的变化并筛选差异基因的表达;运用Monocle包对关键风险基因在不同发育阶段细胞中的表达情况进行分析;利用Kaplan-Meier Plotter在线数据平台分析生存曲线;运用空间转录组技术验证关键基因在组织中的表达映射;多色荧光免疫组化进行临床样本的验证。结果 捕获得到7个巨噬细胞亚群,其中第1亚群仅存在于肿瘤组织中且分泌型磷蛋白1(SPP1)基因高富集。SPP1高表达趋向巨噬细胞M2型极化并处于细胞分化的终末阶段。SPP1+巨噬细胞糖酵解、缺氧、上皮间质化、血管生成等功能活跃,与HNSCC患者的预后呈负相关。结论 SPP1可能成为HNSCC中有价值的预后生物标志物。     

子宫颈HPV相关性乳头状鳞状细胞癌的临床病理分析

目的 探讨子宫颈乳头状鳞状细胞癌(papillary squamous cell carcinoma, PSCC)的临床病理学特征、诊断及鉴别诊断。方法 收集18例子宫颈PSCC临床资料,行HE和免疫组化染色,分析其临床病理特征,并复习相关文献。结果 18例患者年龄30～71岁,平均49岁,镜下活检和手术标本均可见浅表乳头状结构,伴纤维血管轴心,被覆上皮具有子宫颈高级别鳞状上皮内病变(high-grade squamous intraepithelial lesion, HSIL)的特征。17例子宫颈活检病理学检查均为典型的PSCC,1例子宫颈虽有菜花样肿物,但活检标本未见间质浸润,行子宫颈锥切,锥切标本仍未见间质浸润。13例行根治性子宫切除,最后均诊断为子宫颈PSCC,伴间质浸润;4例活检诊断后失访。免疫表型：p16呈弥漫强阳性(块状)染色,p63、CK7阳性,CK20阴性,Ki-67增殖指数>90%,遍布上皮全层。14例行HPV DNA分型检测,其中10例HPV 16阳性(71.4%),2例分别合并HPV 53和HPV 59感染。结论 子宫颈PSCC具有典型的病理形态学表现,...     

头颈部鳞状细胞癌肿瘤微环境中细胞成分研究进展

肿瘤微环境是头颈部鳞状细胞癌中复杂的微生态系统, 微环境中各种细胞直接作用于肿瘤细胞或是通过分泌细胞因子影响下游信号转导通路促进/抑制肿瘤细胞, 在头颈部鳞状细胞癌的发生、发展中发挥着至关重要的作用, 也为未来头颈部鳞状细胞癌的诊治提供新思路。     

头颈部鳞状细胞癌组织中人乳头状瘤病毒的检测及其意义

人乳头状瘤病毒 (humanpapillomavirus,HPV)是一种致瘤性DNA病毒 ,已被普遍公认为人类生殖道肿瘤的重要致病因素。近年来 ,HPV与人类头颈部肿瘤 ,尤其是与头颈部鳞癌的关系日益被人们所重视和研究 ,被认为是继吸烟、饮酒之后的头颈部鳞癌的第三大致病因素。大量研究证实 ,HPV在人类头颈部鳞癌 ,如 :扁桃体癌、舌癌及喉癌原发肿瘤中检出率高 ,而在鼻咽癌中阳性率较低。另外 ,HPV在头颈部鳞癌转移淋巴结中的检测未见报道。基于以上特点 ,本研究试图通过对头颈部不同原发部位的鳞癌转移淋巴结中HPV的检测 ,来探讨借助HPV检测在鉴别原…     

宫颈鳞状细胞癌HPV16/18、p53、p21表达及意义

目的　探讨人乳头状瘤病毒 (HPV) 16型、18型及 p5 3、p2 1基因蛋白的表达情况以及与宫颈癌的关系。 方法　应用免疫组化二步法检测 5 0例宫颈鳞癌、4 0例正常宫颈黏膜中HPV16、HPV18、p5 3、p2 1的表达。肿瘤组分 <6 0岁和≥ 6 0岁 2个年龄组 ,观察HPV感染情况。结果　宫颈鳞癌中HPV16、HPV18、p5 3、p2 1表达分别为 4 8%、2 0 %、5 4 %和 5 0 % ,而正常宫颈黏膜中的表达分别为 10 %、0、0、10 % ,两者经统计学比较差异有显著性 (P <0 0 1) ;<6 0岁组和≥ 6 0岁组HPV16阳性率分别为 84 2 %和 2 5 8% ,年青组明显高于年老组 ,经统计学比较差异有显著性 (P <0 0 1)。结论　 (1)宫颈鳞癌的发生与HPV16、HPV18感染有密切关系 ,提示检测宫颈HPV16、HPV18感染情况对于宫颈鳞癌的随访和早期诊断有着重要的参考价值。 (2 )提示宫颈黏膜在HPV感染后 ,可能在p5 3、p2 1多种癌基因的共同作用导致宫颈鳞癌的发生发展。     

肺鳞状细胞癌中死亡相关蛋白激酶的表达

目的　检测肺鳞状细胞癌中死亡相关蛋白激酶 (DAP K)mRNA表达及细胞凋亡 ,探讨DAP K与细胞凋亡的关系及其在肺鳞状细胞癌发生、发展中的作用。方法　用原位分子杂交法检测 6 0例肺鳞状细胞癌、9例癌旁肺组织DAP KmRNA表达 ;用原位末端标记TUNEL法检测相应组织中细胞凋亡 ,计算凋亡指数 (AI)。结果　肺鳞状细胞癌的DAP KmRNA阳性表达率为 4 6 7% ,癌旁肺组织为 6 7 7% ,其阳性率高于肿瘤组织 (P <0 0 1 )。在肺鳞状细胞癌中 ,高分化癌DAP KmRNA阳性率为 70 % ,低分化癌为 2 3 3% ,高分化癌的DAP KmRNA阳性率高于低分化癌 (P <0 0 1 )。肺鳞状细胞癌的细胞AI为(0 6 72 8± 0 4 2 6 1 ) % ,癌旁肺组织中支气管肺泡上皮细胞AI为 (1 0 2 89± 0 2 4 33) % ,癌旁肺组织的AI高于肿瘤组织 (P<0 0 1 )。在肺鳞状细胞癌中 ,高分化癌的AI为 (0 5 82 3± 0 1 92 2 ) % ,低分化癌为 (0 4 4 6 0± 0 1 92 5 ) % ,高分化癌的AI高于低分化癌 (P <0 0 1 )。DAP KmRNA呈阳性表达的肺癌 ,其AI为 (0 5 31 7± 0 2 0 97) % ;DAP KmRNA呈阴性者 ,其AI为 (0 4 872± 0 1 91 8) % ,两组间差异有显著性 (P <0 0 5 )。在连续切片上 ,DAP KmRNA阳性细胞的分布区域与凋亡阳性细胞的分布相似。DAP KmRNA呈阳性表达     

原发性和继发性甲状腺鳞状细胞癌的诊治分析

目的探讨原发性甲状腺鳞状细胞癌(PSCCT)和继发性甲状腺鳞状细胞癌(SSCCT)的临床特点。方法对北京协和医院收治的17例PSCCT患者和6例SSCCT患者的病例资料进行系统回顾。分析、比较两组患者的临床症状、超声及病理特征。结果女性的发病率高于男性,平均年龄在56岁左右。两组患者最常见的主诉均为颈部肿块。SSCCT组咳嗽的比例高于PSCCT组(P0.01)。PSCCT组肿瘤的平均大小高于SSCCT组(P0.05)。甲状腺乳头状癌(PTC)可同时伴发PSCCT。PSCCT患者平均生存时间为17.1个月,SSCCT患者平均生存时间为13.5个月。可以通过年龄、颈部淋巴结肿大、根治手术、PTC来预测PSCCT患者总体生存率。结论 SCCT具有侵袭性,颈部肿块往往是最常见的主诉。PTC可合并或复发为PSCCT。年龄、颈部淋巴结肿大、根治手术、PTC是PSCCT患者总体生存期(OS)的预测因子。     

胃原发性鳞状细胞癌2例

例1女性,77岁,因腹胀入院.胃镜检查示鳞状细胞癌,遂行全胃切除根治术.患者无吸烟史,术后随访5年,全身CT示无其他部位肿瘤;例2男性,68岁,吸烟史近40年,因呕血入院.胃镜检查示鳞状细胞癌.行胃次全切根治术,术后随访4年,全身CT示无其他部位肿瘤.     

Molecular predictors of clinical outcome in patients with head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) involves the upper aerodigestive tract and can destroy the structure and function of organs involved in voice, speech, taste, smell and hearing, as well as vital structures necessary for survival. HNSCC has long been a treatment challenge because of the high rate of recurrences and of advanced disease at the time of diagnosis. Molecular identification of tissue biomarkers in diagnostic biopsy specimens may not only identify patients at risk for developing HNSCC but may also select patients that may benefit from more aggressive treatment modalities. Several biomarkers studied to date such as the proteins p53, cyclin D1, p16, Cox-2 enzyme, epidermal growth factor and vascular endothelial growth factor receptors, matrix metalloproteinases and the Fhit marker for genomic instability could be manipulated for the therapeutic benefit of these patients. This review presents the most updated information on molecular biomarkers with the greatest prognostic potential in HNSCC and discusses some factors that contribute to the controversy concerning their prognostic importance.     

Heparanase expression in head and neck squamous cell carcinomas is associated with reduced proliferation and improved survival

Mogler C, Herold‐Mende C, Dyckhoff G, Jenetzky E, Beckhove P & Helmke B M
(2011) Histopathology  58 , 944–952
Heparanase expression in head and neck squamous cell carcinomas is associated with reduced proliferation and improved survival Aims: Cellular expression of heparanase, a degrading enzyme of the extracellular matrix, is associated with poorer prognosis in several cancers. The present analysis, has studied the role of heparanase in tumour growth and clinical outcome in patients with head and neck squamous cell carcinoma (HNSCC). Methods and Results: We analysed the cellular expression of the active form of heparanase in 71 human HNSCCs, using immunohistochemistry. The results were compared with clinicopathological data and, in 65 cases with immunoreactivity for the proliferation marker, MIB1. Cellular heparanase expression was detected in 41 of 71 (57.74%) cases; in particular, UICC IV‐stage tumours showed high heparanase levels. Heparanase was localized mainly in the cytoplasm and, to a lesser extent, at the cell membrane. High levels of heparanase were significantly correlated with an almost four‐fold decrease in MIB1 labelling (P = 0.006). Comparison with clinical outcome by multivariate analysis revealed that patients with high‐level heparanase expression had prolonged overall survival (P = 0.029). Conclusions: Although heparanase was mainly found in late‐stage HNSCCs, cellular heparanase expression in HNSCCs was associated with prolonged overall survival. We propose that the proliferation‐reducing effect of high heparanase levels might outweigh the tumour‐promoting effects of heparanase, especially in advanced tumours.     

Loss of desmoglein 1 expression associated with worse prognosis in head and neck squamous cell carcinoma patients

Aims:Mucosal squamous cell carcinomas are the most common head and neck malignancies. We hypothesised that over-expression of intracellular signalling proteins and decreased expression of desmoglein molecules would be associated with aggressive tumour behaviour in patients with head and neck squamous cell carcinoma. Methods: Seventy-eight cases of head and neck squamous cell carcinoma were immunohistochemically stained for desmoglein 1, desmoglein 2, desmoglein 3, p53, bcl-2, vimentin, cyclin D1, p16, p21, p27, E-cadherin, and E2F-1 in paraffin-embedded tissue blocks in a microarray. Results: The disease-specific survival was 56% at 5 years and 49% at 10 years. Expression of the desmoglein isotypes correlated positively with each other except for desmoglein 2 and desmoglein 3, which did not show a significant correlation. Desmoglein 1 and E-cadherin expression also correlated. On univariate analysis, only expression of desmoglein 1 correlated with patient outcome; lack of expression of desmoglein 1 was associated with a significantly worse disease-specific survival (p = 0.035). Hierarchical clustering analysis identified a subgroup of three patients with an immunophenotype distinct from the other tumours, characterised by co-expression of p16, p27, E2F-1 and bcl-2. Further statistical analysis of the prognostic significance of this small subgroup was not possible, but these three patients are alive and well. Conclusions: Decreased expression of desmoglein 1 is associated with a worse prognosis in head and neck squamous cell carcinoma patients. Examination of an extended panel of immunomarkers revealed a rare subtype of squamous cell carcinoma characterised by the expression of multiple proliferation-associated markers and the anti-apoptotic protein, bcl-2; determination of the prognostic significance of this subgroup will require study of a larger case series.     

Human papillomavirus DNA in head and neck squamous cell carcinomas in the Free State,South Africa

Human papillomaviruses (HPVs) have been associated with a subset of head and neck squamous cell carcinomas (HNSCCs). The aim of this study was to determine the prevalence of HPV DNA in archived formalin-fixed paraffin-embedded tissue from patients with histologically confirmed HNSCCs in a South African cohort. A nested PCR was used for the detection of HPV DNA targeting the L1 gene. Positive samples were confirmed using an in-house hemi-nested PCR targeting the E6 gene and genotyped by sequence determination of amplicons. HPV DNA was detected in 57/780 (7.3%) samples, with the highest prevalence being in the sinonasal tract (16.0%) and oropharynx (10.8%). HPV16 was the most frequently detected type, being found in 26/57 (45.6%) positive samples. The prevalence of HPV DNA in HNSCCs found in this study was lower than that found in developed countries