联合检测在非小细胞肺癌中鉴别诊断的价值

目的探讨细胞角蛋白5/6(CK5/6)、细胞角蛋白HMW(CK-HMW)、甲状腺转录因子-1(TTF-1)和细胞角蛋白8/18(CK8/18)联合检测在低分化非小细胞肺癌中鉴别诊断鳞癌和腺癌的价值。方法采用免疫组化(En Vision法)检测CK5/6、HMW、TTF-1和CK8/18在478例肺鳞癌和腺癌中的表达情况并对结果进行分析。结果单个免疫组化指标中,CK5/6和TTF-1对于肺鳞癌和腺癌的鉴别诊断具有较高价值。CK5/6和HMW联合诊断能提高肺鳞癌诊断的特异性和准确度。TTF-1和CK8/18联合诊断能提高肺腺癌诊断的特异性和准确度。结论 CK5/6、HMW、TTF-1和CK8/18的联合检测对于低分化肺鳞癌和腺癌的鉴别诊断具有很高的价值。     

胸水中NapsinA与TTF-1表达在肺腺癌鉴别诊断中的临床意义

目的探讨胃酶样天冬氨酸蛋白酶(Napsin)A和甲状腺转录因子(TTF)-1在胸水沉渣包埋组织中的表达及应用价值。方法用免疫组化SP方法,检测Napsin A和TTF-1在80例肿瘤性胸腔积液标本中的表达情况。结果 (1)Napsin A和TTF-1在胸水沉渣包埋组织中的阳性表达与肺癌组织类型密切相关(P0.05);(2)胸水沉渣包埋组织中Napsin A和TTF-1的表达与肺腺癌分化程度、淋巴结转移及临床分期无关(P0.05)。结论应用胸水沉渣包埋组织免疫组化方法检测Napsin A和TTF-1的阳性表达在肺癌的诊断及鉴别诊断中具有重要价值。     

血清癌胚抗原 细胞角蛋白19片断21-1和神经元特异性烯醇化酶联合检测对肺腺癌 鳞癌化疗预后的价值研究

目的探讨癌胚抗原(CEA)、细胞角蛋白19片断21-1(CYFRA21-1)及神经元特异性烯醇化酶(NSE)检测在化疗后肺腺癌、鳞癌患者预后判断中的临床意义。方法收集2007-01-01—2009-12-31中国医科大学附属第四医院189例确诊后接受一线化疗的肺腺、鳞癌患者,计算2个周期化疗前后3种肿瘤标志物(CEA、CYFRA21-1及NSE)的下降率,观察生存期。结果化疗后肺腺、鳞癌患者CEA、CYFRA21-1、NSE的变化趋势与预后相关,肿瘤标志物较前下降的患者与较前上升的患者相比,生存期明显延长。化疗后CEA下降率预测预后的最佳截断点为63.9%,30.1%,46.8%。联合检测肿瘤标志物的下降率对预后的预测能力较单一检测明显增强,差异均有统计学意义(P<0.001)。结论肺腺、鳞癌患者化疗后CEA、CYFRA21-1和NSE的下降率与患者生存期相关,CEA、CY-FRA21-1和NSE可预测化疗后患者的预后,血清CEA、CYFRA21-1和NSE在化疗期间下降明显者提示预后较好,生存期较长,联合检测较单一检测对预后的提示能力更佳。     

TTF-1联合NspsinA、SP-A、ER和PR在转移性乳腺癌和肺原发性腺癌鉴别中的应用价值

目的探讨甲状腺转录因子(TTF)-1联合天冬氨酸蛋白酶(Nspsin A)、肺泡表面活性蛋白(SP)-A、雌激素受体(ER)和孕激素受体(PR)在转移性乳腺癌和肺原发性腺癌鉴别中的应用价值。方法 48例乳腺癌继发肺癌患者的肺叶切除标本为转移性乳腺癌组,140例已确诊为肺原发性腺癌的肺叶切除标本作为肺原发腺癌组,采用免疫组化法检测两组患者标本中TTF-1联合Nspsin A、SP-A、ER和PR的表达。评价其在转移性乳腺癌和肺原发性腺癌鉴别中的应用价值。结果 TTF-1在肺原发性腺癌组中阳性率为87.9%,在转移性乳腺癌组中呈阴性表达。Napsin A和SPA在肺原发性腺癌组中的阳性率分别为82.1%和77.1%,而在转移性乳腺癌组中呈阴性表达。ER和PR在转移性乳腺癌组(87.5%和70.8%)中的表达显著高于肺原发性腺癌组(2.1%和2.9%)。将TTF-1、Napsin A、SP-A、ER和PR抗体组合鉴别肺内转移性乳腺癌的AUC为0.805,敏感度为85.7%,特异度为80.6%。结论 TTF-1联合Nspsin A、SP-A、ER和PR有助于准确鉴别转移性乳腺癌和肺原发性腺癌,为这类患者的临床分期和个体化治疗提供准确的科学依据。     

血浆长链非编码RNA转移相关肺腺癌转录因子1对肺癌临床诊断价值

目的探讨血浆中长链非编码RNA转移相关肺腺癌转录因子1(MALAT1)对肺癌临床诊断意义。方法分别检测84例肺癌患者(34例腺癌、26例鳞癌、24例小细胞性肺癌)和60例体检健康者血浆中MALAT1、癌胚抗原(CEA)、CK19片段(CYFRA21-1)、鳞状细胞癌抗原(SCC-Ag)和神经元特异性烯醇化酶(NSE)的表达水平,通过logistic回归分析和受试者工作曲线(ROC曲线)分析其灵敏度、特异度等指标。结果MALAT-1在肺癌患者血浆中比健康对照组的表达水平高(P0.01);当临界点(cutoff值)为0.03时,MALAT-1在腺癌中阳性率为70.59%,其诊断肺癌时AUC、灵敏度和特异度分别为0.70、58.33%、81.67%。MALAT-1、NSE和CYFRA21-1三者联合检测肺癌及小细胞性肺癌的AUC分别为0.91、0.98,灵敏度分别为82.14%、95.83%,特异度分别为85.00%、93.33%。MALAT-1在腺癌中AUC、灵敏度和特异度分别为0.81、76.47%、83.33%。结论 MALAT-1可作为肺癌,特别是肺腺癌血清学诊断独立标志物,MALAT-1、NSE和CYFRA21-1三指标联合可显著提高肺癌及不同肺癌病理类型的诊断效能。     

结肠癌转移相关因子-1和间质-上皮细胞转化因子检测在肺腺癌患者并发恶性胸腔积液中的诊断价值

目的探讨结肠癌转移相关因子-1(MACC1)、间质-上皮细胞转化因子(c-MET)联合癌胚抗原(CEA)在肺腺癌患者并发恶性胸腔积液中的诊断价值。方法将91例胸腔积液患者(良性38例,肺腺癌53例)纳入研究,采用ELISA法测定血清和胸腔积液中MACC1、c-MET浓度,放射免疫法测定CEA浓度。结果肺腺癌患者恶性胸腔积液中MACC1、c-MET和CEA浓度明显高于良性患者胸腔积液中的含量(P0.05);两组患者血清中MACC1和c-MET浓度无统计学差异(P0.05)。胸腔积液中MACC1和c-MET含量呈正相关(r=0.728,P0.01)。根据ROC曲线,以MACC1浓度90.98 pg/ml为临界值,对肺腺癌患者并发恶性胸腔积液的诊断灵敏度为62.26%,特异度为84.21%;c-MET浓度757.67ng/ml为临界值,肺腺癌患者恶性胸腔积液的诊断灵敏度为52.83%,特异度为84.21%。MACC1联合cMET检测灵敏度为75.47%,特异度为92.11%;MACC1、c-MET联合CEA诊断的灵敏度为98.10%,特异度为100%。结论 MACC1和c-MET在肺腺癌患者并发恶性胸腔积液的诊断中具有一定价值,联合CEA检测可明显提高诊断的灵敏度和特异度。     

替雷利珠单抗联合白蛋白紫杉醇+奈达铂治疗晚期基因野生型肺腺癌疗效及对血清细胞蛋白19片段21-1、血管内皮生长因子水平和预后的影响

目的 探讨替雷利珠单抗联合白蛋白紫杉醇+奈达铂治疗晚期基因野生型肺腺癌疗效及对血清细胞蛋白19片段(CYFRA)21-1、血管内皮生长因子(VEGF)水平和预后的影响。方法 回顾性分析2018年2月～2020年3月于我院治疗的88例晚期基因野生型肺腺癌患者,依据治疗方案不同分成对照组(46例)与观察组(42例),对照组采用白蛋白紫杉醇+奈达铂治疗,观察组采用替雷利珠联合白蛋白紫杉醇+奈达铂治疗,两组均治疗5个疗程。比较两组患者治疗疗效、治疗前后肿瘤标志物、VEGF水平、治疗期间骨髓抑制发生状况及生存状况。结果 治疗后观察组疾病控制率(DCR)高于对照组,血清CFRA21-1、VEGF及癌胚抗原(CEA)均低于同期对照组;两组患者血清CYFRA21-1、VEGF及CEA水平均低于同组治疗前(P<0.05)。治疗期间,两组患者骨髓抑制发生状况构成比较差异无统计学意义(P>0.05)。随访2年期间,对照组生存率均低于观察组(P<0.05)。结论 晚期基因野生型肺腺癌患者予替雷利珠单抗结合白蛋白紫杉醇+奈达铂治疗可有效控制肿瘤进展,降低患者血清CYFRA21-1及VEGF水平...     

接触蛋白-1在原发性肺鳞状细胞癌组织中的表达及临床意义

目的探讨神经细胞粘附分子-接触蛋白-1(contactin-1, CNTN-1)在原发性肺鳞状细胞癌组织中的表达,并探讨其表达与患者临床病理参数之间的关系。 方法收集63例原发性肺鳞状细胞癌手术石蜡切片标本和20例正常肺上皮组织标本,采用免疫组织化学染色技术检测CNTN-1表达,并分析其与患者临床病理参数之间的关系。 结果63例原发性肺鳞癌组织标本中,阳性表达35例,阴性表达26例,2例因石蜡切片上的标本脱落而无癌组织,CNTN-1在人正常肺泡上皮组织中不表达,在原发性肺鳞状细胞癌组织中广泛表达,阳性率为55.56%(35/63);χ²检验或Fisher精确概率法检验结果显示,CNTN-1阳性表达与患者吸烟和术前淋巴结侵袭显著相关(P<0.05),而CNTN-1差异表达与患者各临床病理参数之间无相关性。 结论CNTN-1是一个潜在的原发性肺鳞状细胞癌患者预后的生物学标志物。     

HPV16/18E6和P53基因蛋白在喉鳞癌中的表达及其相关性研究

目的探讨人乳头瘤病毒16/18型早期蛋白E6(HPV16/18 E6)、P^53基因蛋白在喉鳞癌(LSCC)中的表达及其相关性.方法免疫组化SABC法检测HPV16/18E6和P^53基因蛋白在LSCC及声带息肉中的表达.结果 HPV16/18E6在声带息肉中未见表达,在LSCC中的表达率为40.0%,差异有显著性(P＜0.05). P^53基因蛋白在声带息肉与LSCC中的表达率分别为6.66%和66.2%,差异有显著性(P＜0.05).HPV16/18E6及 P^53基因蛋白的表达与LSCC临床分期、淋巴结转移有关.二者的表达无明显相关性.结论 HPV16/18型感染和P^53基因异常与LSCC发生、发展有关.HPV16/18E6与P^53基因功能异常无明显相关性.     

宫颈鳞癌组织与宫颈正常组织中P16 P53及Beclin-1的表达

目的探讨P16、P53、Beclin-1三种蛋白在宫颈鳞癌组织及宫颈正常组织中的表达及临床病理意义。方法应用免疫组化SP法检测宫颈正常组织组40例及宫颈鳞癌组织组43例P16、P53和Beclin-1蛋白表达水平。结果宫颈鳞癌组织中P16及P53表达阳性率分别为100.0%和86.0%,高于宫颈正常组织的5.0%和5.0%(P均0.05),其表达强度与宫颈鳞癌组织呈正相关。而Beclin-1在宫颈鳞癌组织中表达阳性率为55.8%,正常宫颈组织为85.0%(P0.01),表达强度与宫颈鳞癌组织呈负相关。结论 P16、P53蛋白及Beclin-1蛋白与宫颈鳞癌的发生发展相关,P16和P53的表达随宫颈上皮恶变的进展而增加,而Beclin-1在宫颈恶性病变中的表达明显下调。     

Comparison of clinical stage, therapy response, and patient outcome between squamous cell carcinoma and adenocarcinoma of the esophagus

Purpose: To analyze the differences in clinical stage, pathologic response to chemoradiotherapy, patterns of failure, and overall survival (OS) between patients with squamous cell carcinoma (SCC) and adenocarcinoma (ACA) of the esophagus. Patients and Methods: We stratified patients by two histologies, ACA and SCC, and statistically compared their clinical stage, post-therapy pathologic response, patterns of failure, and OS. Results: Of the 235 patients who underwent preoperative chemoradiotherapy, 42 (18%) had SCC and 193 (82%) had ACA. Among the ACA patients, a significantly larger proportion was male (93% vs 7%; p<0.001), whereas sex was distributed similarly among SCC patients (55% male vs 45% female; p=0.5). A significantly larger percentage of SCC patients were classified as lower TN and overall stage than ACA patients (T2=41% vs 28%, p<0.0001; N0=69% vs 48%, p=0.01; stage II=76% vs 55%, p<0.001). A significantly greater portion of SCCs was categorized as pathologic N0 after treatment (71% vs 65%; p=0.02). Among the pathCR patients in clinical stage II, there were significantly greater proportion of SCC patients (77% vs 63%; p<0.001) than ACA patients. Among the pathCR patients in clinical stage III patients, a significantly greater proportion were ACA patients (38% vs 23%; p<0.001) than SCC patients. The median and 5-yr OS was 53±11 mo and 39% for ACA patients and 35±14 mo and 37% for SCC (median OS, p=0.3). Among pathCR patients, median OS of ACA patients (133 mo) was longer than that of SCC patients but nonsignificant (29 mo; p=0.07); results were similar for non-pathCR patients. DFS results were similar in all subgroups. Among the whole cohort, incidence of local-regional recurrence and distant metastases did not vary significantly. The median time to distant metastases did not vary significantly for pathCR and non-pathCR patients. Conclusions: We believe this is the first study that compares failure outcome of ACA and SCC patients with similar clinical stage after trimodality therapy. Our data suggest that significant differences in clinical stage and post-therapy pathologic stage exist between ACA and SCC. Frequent presence of malignant nodes in the resected specimens of ACA patients resulted in a shorter time-to-metastases suggesting that ACA patients need better systemic control.     

新辅助化疗对宫颈鳞状细胞癌CK5/6和p63蛋白表达的影响

目的探讨新辅助化疗对宫颈鳞状细胞癌(鳞癌)CK5/6和p63蛋白表达的影响。方法对48例临床ⅠB-ⅡB期宫颈鳞癌患者行以顺铂为基础的新辅助化疗3周期,其后3周行手术治疗,观察临床疗效及病理组织学疗效;用免疫组织化学方法检测癌组织化疗前后CK5/6和p63表达情况。结果新辅助化疗临床总有效率为56%(27/48),病理组织学总有效率为50%(24/48),48例患者化疗前癌组织均弥漫表达CK5/6和p63,阳性表达率均为100%,化疗后有癌残留的46例患者癌组织均表达CK5/6和p63,阳性率均为100%(P≥0.05),但阳性表达强度均弱于化疗前。结论新辅助化疗对宫颈鳞癌特异性标记物CK5/6和p63表达无显著影响,CK5/6和p63可用于形态学难确诊的化疗后宫颈鳞癌的诊断与鉴别诊断。     

TSA对甲状腺鳞癌细胞株Akt、p21、mTOR基因表达的影响

目的观察曲古抑菌素A（Trichostatin A,TSA）对甲状腺鳞癌SW579细胞株Akt、mTOR和p21基因表达的影响,探讨TSA抗甲状腺癌的作用机制。方法体外培养SW579细胞,用CCK-8法检测TSA对SW579的生长抑制作用,计算半数抑制浓度。实验分为对照组、TSA组、Wortmannin组、Wortmannin＋TSA组、Rapamycin组,用RT-PCR方法检测SW579细胞Akt、p21及mTOR的mRNA表达,分析各处理组Akt、p21及mTOR基因表达变化。结果 CCK-8结果显示,TSA可明显抑制SW579的增殖,并呈剂量依赖性,半数抑制浓度约为147nmol/L。RT-PCR检测结果表明,与对照组相比,TSA组、Wortmannin组和Wortmannin＋TSA组Akt、mTOR mRNA表达水平明显降低,TSA组p21表达显著上调,Wortmannin组p21表达明显降低,各组mTOR表达均明显降低。结论 TSA在一定浓度范围内对甲状腺鳞癌细胞株SW579有剂量依赖性的增殖抑制作用,其机制可能与TSA降低SW579细胞Akt、mTOR基因的表达,进而再上调p21的表达有关。     

Application of computed tomography-based radiomics in differential diagnosis of adenocarcinoma and squamous cell carcinoma at the esophagogastric junction

BACKGROUNDThe biological behavior of carcinoma of the esophagogastric junction (CEGJ) is different from that of gastric or esophageal cancer. Differentiating squamous cell carcinoma of the esophagogastric junction (SCCEG) from adenocarcinoma of the esophagogastric junction (AEG) can indicate Siewert stage and whether the surgical route for patients with CEGJ is transthoracic or transabdominal, as well as aid in determining the extent of lymph node dissection. With the development of neoadjuvant therapy, preoperative determination of pathological type can help in the selection of neoadjuvant radiotherapy and chemotherapy regimens.AIMTo establish and evaluate computed tomography (CT)-based multiscale and multiphase radiomics models to distinguish SCCEG and AEG preoperatively.METHODSWe retrospectively analyzed the preoperative contrasted-enhanced CT imaging data of single-center patients with pathologically confirmed SCCEG (n = 130) and AEG (n = 130). The data were divided into either a training (n = 182) or a test group (n = 78) at a ratio of 7:3. A total of 1409 radiomics features were separately extracted from two dimensional (2D) or three dimensional (3D) regions of interest in arterial and venous phases. Intra-/inter-observer consistency analysis, correlation analysis, univariate analysis, least absolute shrinkage and selection operator regression, and backward stepwise logical regression were applied for feature selection. Totally, six logistic regression models were established based on 2D and 3D multi-phase features. The receiver operating characteristic curve analysis, the continuous net reclassification improvement (NRI), and the integrated discrimination improvement (IDI) were used for assessing model discrimination performance. Calibration and decision curves were used to assess the calibration and clinical usefulness of the model, respectively.RESULTSThe 2D-venous model (5 features, AUC: 0.849) performed better than 2D-arterial (5 features, AUC: 0.808). The 2D-arterial-venous combined model could further enhance the performance (AUC: 0.869). The 3D-venous model (7 features, AUC: 0.877) performed better than 3D-arterial (10 features, AUC: 0.876). And the 3D-arterial-venous combined model (AUC: 0.904) outperformed other single-phase-based models. The venous model showed a positive improvement compared with the arterial model (NRI > 0, IDI > 0), and the 3D-venous and combined models showed a significant positive improvement compared with the 2D-venous and combined models (P < 0.05). Decision curve analysis showed that combined 3D-arterial-venous model and 3D-venous model had a higher net clinical benefit within the same threshold probability range in the test group.CONCLUSIONThe combined arterial-venous CT radiomics model based on 3D segmentation can improve the performance in differentiating EGJ squamous cell carcinoma from adenocarcinoma.     

Prognostic significance of PD-L1 expression and CD8+ TILs density for disease-free survival in surgically resected lung squamous cell carcinoma: a retrospective study

BackgroundThis study sought to depict the genomic landscape of patients with surgically resected lung squamous cell carcinoma (LUSC) and its relationship with clinical outcome indicators.MethodsWe retrospectively collected the clinical data of 180 patients from the electronic medical records and applied targeted sequencing and immunohistochemistry (IHC) to depict the genomic landscape, including the tumor mutation burden (TMB), programmed cell death-ligand 1 (PD-L1), and cluster of differentiation CD8⁺ tumor-infiltrating lymphocytes (CD8⁺ TILs). And comparative analysis and survival analysis of these parameters were conducted to find prognostic factors for clinical outcome.ResultsPD-L1+ tumor cells were observed in 75 (41.7%) of the patients, the median rate of CD8⁺ TILs was 11.5 [4, 24], and the median TMB was 9.4 (7.5–13.7) mutations per megabase (mut/Mb). Patched receptor 1 (PTCH1) gene mutation frequency was significantly associated with CD8⁺ TILs density (12% vs. 1%; P=0.024). High PD-L1 expression and CD8⁺ TILs+ were significantly associated with longer disease-free survival (DFS), and a further subgroup analysis revealed that both were significantly correlated with the DFS of stage I/II patients but not stage III patients.ConclusionsThe results suggest that only PTCH1 gene mutation frequency was correlated with CD8⁺ TILs density. Additionally, intense CD8⁺ TILs density and high PD-L1 expression were found to be associated with longer DFS. Our findings provide insights into the precise treatment strategy for surgically resected LUSC patients.     

Prognostic significance of the expression of c-fos,c-jun and c-erbB-1 oncogene products in human squamous cell lung carcinomas

The expression of the oncogenes c-fos, c-jun, c-myc, c-erbB-1 and c-erbB-2 at the protein level was analyzed in squamous cell lung carcinomas of 121 patients by means of immunohistochemistry. Patients with overexpression of proteins encoded by the oncogenes c-fos, c-jun and c-erbB-1 had significantly shorter survival times than these without overexpression of these oncogene products (c-fos:p=0.009; c-jun:p=0.029; c-erbB-1:p=0.018). No significant correlations were found between the expression of c-myc and c-erbB-2 products and the survival of the patients. In addition to the univariate analyses (Kaplan-Meier-estimates) multivariate analyses (Cox-regression-model) revealed that protein expression of the oncogenes c-fos, c-jun and c-erbB1 are significant prognostic factors in addition to staging.     

Genetic polymorphisms in cytochrome P4502E1, alcohol and aldehyde dehydrogenases and the risk of esophageal squamous cell carcinoma in Gansu Chinese males

AIM：To evaluate the association between genetic polymorphisms in CYP2E1, ALDH2 and ADH1B and the risk of esophageal squamous cell carcinoma （ESCC） in a high risk area of Gansu Province, in Chinese males.
METHODS： A case-control study was conducted to investigate the genetic polymorphisms of these enzymes （CYP2E1 ＊c1/＊c2, ALDH2 ＊1/＊2 and ADH1B ＊1/＊1 genotypes）. A total of 80 esophageal cancer cases and 480 controls were recruited.
RESULTS： Compared with controls, cases had a greater prevalence of heavier alcohol consumption （53.8% vs 16.2%） and a higher proportion of alcohol drinkers with 〉 30 drink-years （28.8% vs 13.5%）. Heavier alcohol consumption and alcohol drinking with 〉 30 drink- years increased the risk of ESCC, with ORs （95% CI） of 3.20 （1.32-9.65） and 1.68 （0.96-3.21）. CYP2E1 （＊c1/＊c1）, ALDH2 （＊1/＊2） and ADH1B （＊1/＊1） genotype frequencies were higher among patients with squamous cell carcinomas, at a level close to statistical significance （P = 0.014; P = 0.094; P = 0.0001 respectively）. There were synergistic interactions among alcohol drinking and ALDH2, ADH1B and CYP2E1 genotypes. The risk of the ESCC in moderate-to-heavy drinkers with an inactive ALDH2 encoded by ALDH2 ＊1/＊2 as well as ADH1B encoded by ADH1B ＊1/＊1 and CYP2E1 encoded by CYP2E1 ＊c1/＊c1 was higher than that in the never/rare-to-light drinkers with an active ALDH2 （＊1/＊1 genotype） as well as ADH1B （＊1/＊2 ＋ ＊2/＊2） and CYP2E1 （＊c1/＊c2 ＋ ＊c2/＊c2） genotypes, with a statistically significant difference; ORs （95% CI） of 8.58 （3.28-22.68）, 27.12 （8.52-70.19） and 7.64 （2.82-11.31） respectively. The risk of the ESCC in moderate-to-heavy drinkers with ALDH2 （＊1/＊2） combined the ADH1B （＊1/＊1） genotype or ALDH2 （＊1/＊2） combined the CYP2E1 （＊c1/＊c1） genotype leads to synergistic interactions, higher than drinkers with ALDH2 （＊1/＊1） ＋ ADH1B （＊1/＊2 ＋ ＊2/＊