Immunohistochemical molecular markers as predictors of curability of endoscopically resected submucosal colorectal cancer

AIM: To clarify the usefulness of immunohistochemical molecular markers in predicting lymph node metastasis of submucosal colorectal cancer. METHODS: We examined microvessel density, lymphatic vessel density, the Ki-67 labeling index, expression of MUC1 and Matrix metalloproteinase-7 (MMP-7) in tumor cells, and expression of cathepsin D in stromal cells at the invasive front by immunostaining of samples resected from 214 patients with submucosal colorectal cancer. Pathologic features were assessed on hematoxylin-eosin- stained samples. We evaluated the relations between clinicopathologic/immunohistochemical features and lymph node metastasis. RESULTS: Lesions of the superficial type, with an unfavorable histologic grade, budding, lymphatic involvement, high microvessel density (≥ 40), high lymphatic vessel density (≥ 9), high Ki-67 labeling index (≥ 42), and positivity of MUC1, cathepsin D, and MMP-7 showed a significantly high incidence of lymph node metastasis. Multivariate analysis revealed that high microvessel density, unfavorable histologic grade, cathepsin D positivity, high lymphatic vessel density, superficial type, budding, and MUC1 positivity were independent risk factors for lymph node metastasis.A combined examination with four independent immunohistochemical markers (microvessel density, cathepsin D, lymphatic vessel density, and MUC1) revealed that all lesions that were negative for all markers or positive for only one marker were negative for lymph node metastasis. CONCLUSION: Analysis of a combination of immuno- histochemical molecular markers in endoscopically resected specimens of submucosal colorectal cancer allows prediction of curability regardless of the pathologic features visible of hematoxylin-eosin-stained sections.

Endoscopic and surgical resection of T1a/T1b esophageal neoplasms: A systematic review

AIM: To investigate potential therapeutic recommendations for endoscopic and surgical resection of T1a/ T1b esophageal neoplasms. METHODS: A thorough search of electronic databases MEDLINE, Embase, Pubmed and Cochrane Library, from 1997 up to January 2011 was performed. An analysis was carried out, pooling the effects of outcomes of 4241 patients enrolled in 80 retrospective studies. For comparisons across studies, each reporting on only one endoscopic method, we used a random effects meta-regression of the log-odds of the outcome of treatment in each study. "Neural networks" as a data mining technique was employed in order to establish a prediction model of lymph node status in superficial submucosal esophageal carcinoma. Another data mining technique, the "feature selection and root cause analysis", was used to identify the most impor-tant predictors of local recurrence and metachronous cancer development in endoscopically resected patients, and lymph node positivity in squamous carcinoma (SCC) and adenocarcinoma (ADC) separately in surgically resected patients. RESULTS: Endoscopically resected patients: Low grade dysplasia was observed in 4% of patients, high grade dysplasia in 14.6%, carcinoma in situ in 19%, mucosal cancer in 54%, and submucosal cancer in 16% of patients. There were no significant differences between endoscopic mucosal resection and endoscopic submucosal dissection (ESD) for the following parameters: complications, patients submitted to surgery, positive margins, lymph node positivity, local recurrence and metachronous cancer. With regard to piecemeal resection, ESD performed better since the number of cases was significantly less [coefficient: -7.709438, 95%CI: (-11.03803, -4.380844), P < 0.001]; hence local recurrence rates were significantly lower [coefficient: -4.033528, 95%CI: (-6.151498, -1.915559),P < 0.01]. A higher rate of esophageal stenosis was observed following ESD [coefficient: 7.322266, 95%CI: (3.810146, 10.83439), P < 0.001]. A significantly greater number of SCC patients were submitted to surgery (log-odds, ADC: -2.1206 ± 0.6249 vs SCC: 4.1356 ± 0.4038, P < 0.05). The odds for re-classification of tumor stage after endoscopic resection were 53% and 39% for ADC and SCC, respectively. Local tumor recurrence was best predicted by grade 3 differentiation and piecemeal resection, metachronous cancer development by the carcinoma in situ component, and lymph node positivity by lymphovascular invasion. With regard to surgically resected patients: Significant differences in patients with positive lymph nodes were observed between ADC and SCC [coefficient: 1.889569, 95%CI: (0.3945146, 3.384624), P<0.01). In contrast, lymphovascular and microvascular invasion and grade 3 patients between histologic types were comparable, the respective rank order of the predictors of lymph node positivity was: Grade 3, lymphovascular invasion (L+), microvascular invasion (V+), submucosal (Sm) 3 invasion, Sm2 invasion and Sm1 invasion. Histologic type (ADC/SCC) was not included in the model. The best predictors for SCC lymph node positivity were Sm3 invasion and (V+). For ADC, the most important predictor was (L+). CONCLUSION: Local tumor recurrence is predicted by grade 3, metachronous cancer by the carcinoma insitu component, and lymph node positivity by L+. T1b cancer should be treated with surgical resection.

EGFR与HER2对非小细胞肺癌的预后观察

目的:探讨传统的非小细胞肺癌预后因素与表皮生长因子等生物学新预后因素结合对非小细胞肺癌的预后作用。方法:复习116例非小细胞肺癌手术病例临床病理资料及随访资料,观察常规HE染色切片判断血管浸润及淋巴管浸润,用免疫组化法测定病灶的EGFR、HER2的表达,再用Cox模型进行生存分析。结果:NSCLC组EGFR、HER2、BVI、LVI的阳性表达率分别为42.24%、43.10%、44.83%、31.90%。BVI阴、阳性组术后生存期比较P=0.006,无瘤生存期比较P=0.001;LVI阴、阳性组术后生存期、无瘤生存期比较P分别为0.239和0.048;EGFR阴、阳性组术后生存期、无瘤生存期比较P分别为0.117及0.217;HER2阴、阳性组术后生存期、无瘤生存期比较P分别为0.073和0.053。进入影响生存期多因素模型的为N分期、HER2、TNM分期及手术方式(P分别为0.006、0.01、0.019和0.022)。结论:13项临床病理和生物因素结合起来进行多变量Cox回归分析,影响生存期的因素为:N分期、HER2、TNM分期及手术方式。影响无瘤生存期的因素为:BVI、TNM分期和N分期。

乳腺癌淋巴血管浸润的MRI 影像研究

目的分析乳腺癌患者淋巴血管浸润的磁共振成像(MRI)影像特征。方法采用回顾性分析法,对2020年6月—2022年6月期间郑州大学附属肿瘤医院收治的80例乳腺癌患图像展开分析。依据患者的术前MR检查和术后病理证实的淋巴血管浸润情况分为浸润组(n=25)和非浸润组(n=55)。比较两组临床资料及MRI征象、MRI表现、时间-强度曲线(TIC)类型,并分析MRI诊断效能。结果与非浸润组相比,浸润组患者腋窝淋巴结肿大、瘤周水肿的占比升高,ADC值降低,差异有统计学意义(P<0.05)。与非浸润组相比,浸润组患者的MRI边缘毛刺、边缘模糊、内部坏死的占比升高,差异有统计学意义(P<0.05)。与非浸润组相比,浸润组患者TICⅢ型的占比升高,差异有统计学意义(P<0.05)。以病理检测结果为金标准,MRI检查时发现乳腺癌淋巴血管浸润性病灶27个,占比31.40%,非浸润性病灶59个,占比68.60%。MRI诊断符合度、灵敏度、特异度分别为88.89%、93.22%、91.86%,结论MRI对于乳腺癌患者淋巴血管浸润有一定诊断价值,患者多表现出腋窝淋巴结肿大、瘤周水肿、ADC值降低和MRI边缘毛刺、模糊、内部坏死,同时对于TICⅢ型患者也应加强监测。

子宫内膜癌患者淋巴管间隙浸润预测因素研究现状

淋巴管间隙浸润(LVSI)状态,是影响子宫内膜癌(EC)患者的预后因素之一。目前对LVSI状态,主要依靠手术切除组织标本的组织病理学检测结果进行判断,尚具有一定局限性。关于LVSI状态预测EC患者预后的相关研究的分子水平检测,包括DNA及RNA与相关蛋白检测,这些均有助于预测EC患者的LVSI状态。根据EC患者临床数据开发的LVSI风险预测模型,如影像学数据及肿瘤标志物等相关预测模型,均可有助于临床判断LVSI状态,从而预测EC患者预后。笔者拟就目前关于EC患者LVSI状态的分子预测、免疫组织化学预测及LVSI状态风险预测模型的最新研究进展现状进行阐述,旨在为临床对EC患者的诊断及治疗方案制定提供参考。

表浅食管鳞癌黏膜下深部浸润发生淋巴结转移的危险因素分析及风险分层

目的探索表浅食管鳞癌黏膜下深部浸润淋巴结转移的危险因素,在此基础上构建预测淋巴结转移风险的评分系统,并初步评价评分系统的临床应用价值。方法 2005-2017年南京大学附属鼓楼医院267例外科术后病理证实为黏膜下深部浸润(距黏膜肌层≥200 μm)的表浅食管鳞癌病例纳入回顾性分析,采用多元Logistic回归分析探索淋巴结转移的独立危险因素,选取P<0.1的自变量建立危险因素评分系统并对自变量赋分,根据受试者工作特征(receiver operating characteristic,ROC)曲线分析的临界值对267例病例进行风险分组,淋巴结转移率行多组间对比分析。结果 267例表浅食管鳞癌黏膜下深部浸润者中,71例(26.59%)术后病理证实存在淋巴结转移。多元Logistic回归分析显示:分化程度为中度或低度(P=0.015,OR=2.802,95%CI:1.225~6.409)、血管侵犯(P=0.043,OR=3.450,95%CI:1.040~11.445)、淋巴管侵犯(P<0.001,OR=36.985,95%CI:13.699~99.856)为淋巴结转移的独立危险因素,黏膜肌层增生异常不是淋巴结转移的独立危险因素(P=0.081,OR=2.005,95%CI:0.918~4.380),但P<0.1。根据上述4个因素建立评分系统,黏膜肌层增生异常赋1分、分化程度为中度或低度赋1分、血管侵犯赋2分、淋巴管侵犯赋5分,ROC曲线分析显示淋巴结转移的最佳诊断界点为评分>2分,将267例病例分为低危组(评分0~1分,n=143)、中危组(评分2~5分,n=79)和高危组(评分6~9分,n=45),3组间淋巴结转移率比较差异有统计学意义(χ^(2)=119.712,P<0.001),且趋势卡方检验结果显示3组淋巴结转移率具有线性上升趋势(χ^(2)=109.298,P<0.001)。结论中度和低度分化、血管侵犯、淋巴管侵犯为表浅食管鳞癌黏膜下深部浸润发生淋巴结转移的独立危险因素,上述3个因素结合黏膜肌层增生异常构建的淋巴结转移风险评估系统具有较好的临床应用价值,有助于个体化指导临床决策,对术后管理具有重要意义。

常规苏木精-伊红染色诊断早期胃癌黏膜下淋巴管浸润状况的价值

目的评价常规苏木精-伊红染色诊断早期胃癌黏膜下淋巴管浸润状况的价值。方法4420例接受剖腹胃癌D2根治术的早期胃癌．常规方法行苏木精-伊红染色检测黏膜下淋巴管浸润状况，并与病理诊断淋巴结转移状况作比较。结果全组早期胃癌患者中，常规苏木精-伊红染色诊断黏膜下淋巴管浸润的灵敏度、特异度、准确度、阳性预测值和阴性预测值分别为54．5％、82．0％、78．9％、27．4％和93．5％；其中2426例局限于黏膜内者分别为14．5％、98．0％、95．8％、15．8％和97．8％；而1994例侵及黏膜下层者则分别为60．3％、57．8％、58．3％、28．1％和84．2％。黏膜下淋巴管浸润阳性率与淋巴结转移阳性率显著相关（P〈0.01）；但与早期胃癌的预后无关（P〉0.05）。黏膜下淋巴管浸润阳性组和阴性组术后5年生存率分别为84．4％和87．3％．中位生存期分别为6998d和7237d，平均生存期分别为6163．9d和6042．6d（P=0．2495）。结论常规苏木精-伊红染色准确度过低．不适合于诊断早期胃癌黏膜下淋巴管浸润状况。

早期子宫内膜癌腹腔镜手术与假性脉管浸润发生率的关系分析

目的分析早期子宫内膜癌腹腔镜手术和假性脉管浸润发生率之间的关联。方法收集本院2016年1月至2018年10月经治早期子宫内膜癌且病例资料完整者共90例。根据手术方式将其分为腹腔镜组(45例)与开腹组(45例)。由2位病理科专家分别对患者的病理切片进行阅片,记录并鉴别淋巴脉管间隙浸润(LVSI)、假性脉管浸润(PVI),将病理判读信息与病例资料进行比较。结果结果显示,腹腔镜组与开腹组病理分级未见统计学差异(P>0.05)。90例患者中,脉管内可见肿瘤细胞团者30例,其中LVSI者21例、PVI者13例,LVSI及PVI并存者4例。两组脉管内肿瘤细胞团及LVSI发生率无差异(P>0.05)。腹腔镜组PVI发生率(22.22%)高于开腹组(6.67%),有统计学差异(P<0.05)。腹腔镜组7例PVI均表现为外层肌层厚壁大血管中可见癌栓,伴间质组织等。随访1年,共4例肿瘤复发,病理类型均为低分化子宫内膜样腺癌,其中2例为LVSI合并PVI者(腹腔镜组);1例为LVSI(开腹组);1例为PVI(开腹组)。结论早期子宫内膜癌腹腔镜手术更易发生PVI,应引起临床重视。