Comparison of DNA hypermethylation patterns in different types of uterine cancer: cervical squamous cell carcinoma, cervical adenocarcinoma and endometrial adenocarcinoma

The incidence of cervical adenocarcinoma (CA) is rising, whereas the incidence of cervical squamous cell carcinoma (CSCC) continues to decrease. However, it is still unclear whether different molecular characteristics underlie these 2 types of cervical carcinoma. To better understand the epigenetic characteristics of cervical carcinoma, we investigated the DNA promoter hypermethylation profiles in CA and CSCC. In addition, we investigated whether DNA hypermethylation patterns might be used for the molecular diagnosis of CA and endometrial adenocarcinoma (EA). Using the bisulfite-modification technique and methylation-specific PCR, we examined the aberrant promoter hypermethylation patterns of 9 tumor suppressor genes (APC, DAPK, CDH1, HLTF, hMLH1, p16, RASSF1A, THBS1 and TIMP3) in 62 CSCCs, 30 CAs and 21 EAs. After Bonferroni correction adjustment (statistically significant at p < 0.0055), we found that the aberrant hypermethylations of CDH1 and DAPK were more frequent in CSCCs than in CAs (80.6% vs. 43.3%, p = 0.001; 77.4% vs. 46.7%, p = 0.005), whereas HLTF and TIMP3 were more frequently methylated in CAs (3.2% vs. 43.3%, p < 0.001; 8.1% vs. 53.3%, p = 0.001). The hypermethylations of RASSF1A and APC were more frequent in CAs than in CSCCs, but this was not significant (9.7% vs. 33.3%, p = 0.008; and 14.5% vs. 40.0%, respectively, p = 0.009). In addition, RASSF1A hypermethylation was significantly more frequent in EAs than in CAs (81.0% vs. 33.3%, p = 0.001). In conclusion, the existence of these unique methylation patterns in these cancers suggests that their tumorigenesis may involve different epigenetic mechanisms.     

宫颈胃型黏液腺癌的MRI表现

目的 分析宫颈胃型黏液腺癌（GAS）的MRI表现,提高诊断准确率。 方法 回顾性收集12例GAS病人的MRI影像资料,观察肿瘤信号特点、生长部位、生长方式及浸润肌层深度,并绘制动态增强扫描的时间-信号强度曲线（TIC）。 结果 宫颈GAS在MRI上表现为宫颈内生型肿块,其中实性4例,囊实性8例。肿块囊性部分在T₂WI及脂肪抑制（FS）T₂WI上表现为弥漫或簇状分布,大小不一,多位于深肌层。肿块实性成分及囊壁在扩散加权成像上呈高信号,动态增强扫描呈明显持续性强化,11例强化程度高于正常子宫肌层。TIC表现为Ⅱ型11例,Ⅰ型1例。 结论 GAS的MRI影像表现具有特征性,可提供诊断线索。     

河南林州地区贲门癌和癌旁组织中p16基因启动子甲基化及蛋白表达

目的探讨贲门癌变过程中p16基因启动子区甲基化和p16蛋白表达变化特征和规律及其相互关系。方法采用甲基化特异PCR（MSP）及免疫组化方法,检测林州地区32例贲门癌患者癌组织、癌旁不典型增生组织和正常组织p16基因启动子区甲基化状态及蛋白表达情况。结果p16基因在癌组织中表达缺失18例（56%）,不典型增生组织中表达缺失8例（73%）;26例（81%）癌组织、7例（64%）不典型增生组织和18例（67%）正常组织发生了p16基因启动子区的甲基化。贲门癌组织中p16基因甲基化与表达缺失一致率为56%。差异无统计学意义,P〉0.05。结论p16蛋白表达缺失可能是贲门癌变过程中的重要分子事件,p16基因启动子区甲基化可能是导致其蛋白表达缺失的机制之一。     

食管腺癌患者血清中脂联素与炎症细胞因子水平的相关性探讨

目的:探讨食管腺癌（esophageal adenocarcinoma,EAC）患者血清中脂联素与炎症细胞因子水平及肿瘤组织病理特点之间的相关性,分析脂联素是否通过调节食管组织炎症而参与抑制肿瘤的进展。方法:收集25例健康人、23例Barrett食管（Barrett's esophagus,BE）患者和18例EAC患者。登记临床病例资料;采集空腹静脉血,采用ELISA法检测血清中脂联素和TNF-α、IL-8、IL-6水平并分析其相关性;进行HE染色观察食管组织局部炎症情况。结果:健康对照组、BE组、EAC组三组间相比较发现,随着食管病变的加重,食管局部炎症细胞浸润越明显,同时检测到血清中TNF-α、IL-8、IL-6水平逐渐升高,相反血清脂联素水平逐渐降低;相关性分析结果显示血清炎症细胞因子水平与脂联素水平间存在着负相关关系。结论:EAC发病过程中,食管局部炎症反应逐渐加重,血清炎症细胞因子水平逐渐升高,而脂联素水平逐渐降低,两者之间存在着明显的负相关关系。由此可知,低脂联素血症可能与EAC发生和进展过程中持续存在的慢性炎症有关。     

In vivo induction of neoplastic growth in nude mouse connective tissue adjacent to xenografted human tumors

Summary Induction of neoplastic growth of murine stroma cells within the human tumor xenograft was observed after serial passage of CEA and 2-microglobulin producing human colonic SLu tumor xenografts in nu/nu BALB/c mice. Mouse tumors within the human tumor xenografts wre identified using specific immunohistologic staining techniques for mouse histocompatibility marker or human CEA. These mixed tumors could be distinguished from normal human tumor xenografts by a different relationship between development of the tumor marker in the serum and tumor size. We were able to establish transformed murine cells from human xenografts, either induced by SC injection of 1×10⁶ tumor cells of the SLu cell line or by human SLu or mammary carcinoma tissue serially passaged in athymic animals. The established human and murine cell lines were characterized by cytogenetic methods. Transformed murine cells were then continuously passaged in tissue culture. The transformed mouse fibroblasts proved to possess tumorigenicity in nude mice. In the case of SLu-derived mouse tumor cells, tumors also developed in the immunocompetent BALB/c mice using 1×10⁶ to 5×10⁶ tumor cells for SC transplantation.     

黄芩苷干预肺腺癌细胞前后肿瘤细胞侵袭能力的变化

目的研究黄芩苷(baicalin)对人肺腺癌细胞株A549侵袭能力的影响,探讨baicalin抑制肺腺癌细胞侵袭能力的相关机制。方法分别用0、0.5、1、2、4、8mg/Lbaicalin处理A549细胞株,对照组加等量0.5%DMSO,孵育48h后,细胞划痕试验测定细胞迁移抑制率;分别用上述浓度的baicalin处理A549细胞株16h,Transwell小室侵袭试验测定细胞侵袭抑制率;2mg/Lbaicalin处理细胞48h,RT-PCR方法分别测定基质金属蛋白酶(MMP)-2、MMP-9、细胞间黏附分子(ICAM)-1的mRNA表达。结果 baicalin可明显抑制人肺腺癌细胞株A549的迁移和侵袭,与对照组(0mg/Lbaicalin)比较,baicalin处理组MMP-2、MMP-9、ICAM-1mRNA表达和活性均显著下降(均P<0.05)。结论 baicalin对人肺腺癌细胞的侵袭能力有明显抑制作用,其机制可能与下调MMP-2、MMP-9、ICAM-1表达有关。     

P33ING1b蛋白在胃腺癌组织中的表达意义

目的探讨P33ING1b蛋白在胃腺癌中的表达意义。方法采用免疫组化SP法检测73例胃腺癌及30例正常胃黏膜中P33ING1b蛋白的表达,并分析其与各临床指标的关系。结果 P33ING1b蛋白在正常胃黏膜组织中的阳性表达率为97.0%（29/30）,远高于其在胃腺癌中的阳性率60.0%（44/73）,差异有统计学意义（P〈0.05）;P33ING1b蛋白在胃腺癌中的表达与患者性别、年龄、肿瘤大小、浸润深度及淋巴结转移情况均无明显相关性（P〉0.05）;但与肿瘤分化高低有关,即高分化组的阳性表达率（76.0%）明显高于低分化组的阳性表达率（44.0%）,二者比较差异有统计学意义（P〈0.05）。结论 P33ING1b蛋白在胃腺癌中的表达下调及表达部位的改变,可能与胃腺癌的发生有关;胃腺癌高分化组中P33ING1b蛋白的阳性表达率明显高于低分化组,提示P33ING1b蛋白可能与胃腺癌的组织分化程度有关。     

Rare SP-A alleles and the SP-A1-6A(4) allele associate with risk for lung carcinoma

Next to cigarette smoking, genetic factors may contribute to lung cancer risk. Pulmonary surfactant components may mediate response to inhaled carcinogenic substances and/or play a role in lung function and inflammation. We studied associations between surfactant protein (SP) genetic variants and risk in lung cancer subgroups. Samples (n=308) were genotyped for SP-A1, -A2, -B, and -D marker alleles. These included 99 patients with small cell lung carcinoma (SCLC, n=31), or non-SCLC (NSCLC, n=68) consisting of squamous cell carcinoma (SCC, n=35), and adenocarcinoma (AC) (n=23); controls (n=99) matched by age, sex, and smoking status (clinical control) to SCLC and NSCLC; and 110 healthy individuals (population control). We found (a) no significant marker associations with SCLC, (b) rare SP-A2 (1A9) and SP-A1 (6A11) alleles associate with NSCLC risk when compared with population control, (c) the same alleles (1A9, 6A11) associate with risk for AC when compared with population (6A11) or clinical control (1A9), and (d) the SP-A1-6A4 allele (found in approximately 10% of the population) associates with SCC, when compared with population or clinical control. A correlation between SP-A variants and lung cancer susceptibility appears to exist, indicating that SP-A alleles may be useful markers of lung cancer risk.     

鼻腔鼻窦非肠型腺癌6例临床分析

目的 以临床病例结合文献分析原发性鼻腔鼻窦非肠型腺癌（non-ITAC）的临床特性和病理免疫学特征,以期给临床医生在今后的诊疗中提供参考。方法 回顾性分析2014—2020年于北京协和医院经手术病理确诊的6例鼻腔鼻窦non-ITAC患者的临床资料和影像学、病理免疫学特点。结果 6例患者中男4例,女2例,年龄29~72岁,平均年龄54.8岁,其中4例为高级别non-ITAC,2例为低级别non-ITAC。临床表现以涕中或痰中带血、鼻塞等为主。4例男性均有吸烟史,其中1例工作中接触木屑较多。治疗方案为手术或术后加放疗或放/化疗。免疫组化结果：6例患者CK7均为阳性,其中4例患者P63为阴性;4例高级别non-ITAC患者Ki-67增殖指数为60%~90%,低级别non-ITAC患者Ki-67增殖指数1%~2%。随访至今,1例患者因肺转移死亡,其余患者均未有复发或转移。结论 鼻腔鼻窦non-ITAC患者临床表现及影像学对诊断有重要意义,病理免疫学对分级、治疗方案和预后有指导作用。     

HIF-1α与MTA-1在子宫内膜癌中的表达及意义

目的研究缺氧诱导因子-1α（HIF-1α）、肿瘤转移相关基因-1（MTA-1）在子宫内膜癌、子宫内膜增生过长及正常子宫内膜组织中的表达水平及其临床意义。方法选择2000—2008年我院行手术切除或门诊刮取的子宫内膜癌165例、子宫内膜增生过长120例及正常子宫内膜120例。应用免疫组织化学EnVision方法分别检测各类子宫内膜标本组织中的HIF-1α与MTA-1的表达情况,分析不同病理类型、临床分期、淋巴结转移等条件下二者的表达变化。结果在正常子宫内膜组织、子宫内膜增生过长及子宫内膜癌中HIF-1α蛋白表达阳性率比较,差异有显著性意义（χ^2=19.156,P〈0.01）;HIF-1α蛋白随着肌层浸润深度的加深和淋巴结的转移其阳性率逐渐上升,差异有统计学意义（P〈0.01或P〈0.05）;MTA-1蛋白在正常子宫内膜组织及肿瘤间质表达缺失,在子宫内膜增生过长及子宫内膜癌中MTA-1蛋白表达阳性率比较,差异有极显著性（χ^2=32.782,P〈0.01）;随着病理分级增加和肌层浸润深度的加深,MTA-1蛋白的阳性表达率增高,且其增高趋势有统计学意义（P〈0.01）;45例子宫内膜癌组织中,MTA-1和HIF-1α表达进行相关系数分析,二者呈正相关（rs=0．659,P〈0．01）。结论：HIF-1α与MTA-1在子宫内膜癌的发生发展中起着重要作用,可能作为肿瘤生物学行为的标志,并成为抗肿瘤治疗的新靶向。