pathological features

病理特征
  • 文章类型: English Abstract
    观察人体细胞蛋白3(MATN3)的表达与病理特征之间的关系,耐药性,基于免疫组织化学方法的胃癌预后。
    纳入了2022年1月至2022年12月在蚌埠医学院第一附属医院治疗的100例胃癌患者。免疫组化法检测MATN3在胃癌组织和癌旁组织中的表达。在病理特征之间比较MATN3的表达。根据化疗耐药情况将患者分为敏感组和耐药组,并比较这些组之间的MATN3表达。采用Kaplan-Meier生存曲线分析MATN3与胃癌患者无复发生存期(RFS)和总生存期(OS)的关系。采用单因素和多因素Cox回归分析影响胃癌患者预后的因素。用MATN3转染人胃癌细胞MGC803。将细胞分为高表达组(LV-MATN3组)及其对照组(LV-NC组)和低表达组(sh-MATN3组)及其对照组(sh-NC组)。使用CCK8测定法评估细胞增殖,使用Transwell测定法评估细胞迁移和侵袭,使用RT-qPCR测量MATN3mRNA表达水平。通过皮下注射MATN3转染的MGC-803细胞构建裸鼠异种移植模型,并使用RT-qPCR测量肿瘤组织中MATN3mRNA的表达水平。
    免疫组化结果显示,MATN3在胃癌组织中的高表达率(64.00%,64/100)与邻近非癌组织相比(31.00%,31/100)(P<0.05)。MATN3高表达与年龄≥60岁有关,肿瘤在胃体的位置,肿瘤大小≥5cm,淋巴结转移(N1-N3),组织学分化(中度至高度),肿瘤浸润深度(T3-T4),TNM分期(Ⅲ-Ⅳ期),远处器官转移,复发,死亡率(P<0.05)。在化疗耐药的患者中,抗性组MATN3高表达率为79.49%(31/39),敏感组为54.10%(33/61)(P<0.05)。随访时间11~22个月,随访率97.00%,失访3例。Kaplan-Meier生存曲线分析显示,MATN3高表达患者的RFS和OS明显低于MATN3低表达患者(RFS:log-rank=17.291,P<0.001;OS:log-rank=21.719,P<0.001)。多变量Cox分析确定了MATN3的高表达(风险比[HR]=2.291,95%置信区间[CI]:1.268-5.392),肿瘤在胃体中的位置(HR=2.057,95%CI:1.441-5.666),淋巴结转移(N1-N3)(HR=2.011,95%CI:1.010-2.274),肿瘤浸润深度(T3-T4)(H=2.977,95%CI:1.032-7.853),TNM分期Ⅲ-Ⅳ期(HR=2.008,95%CI:1.049-3.902),远处器官转移(HR=2.505,95%CI:1.529~5.000)是影响RFS和OS的独立危险因素(P<0.05)。细胞和动物实验表明,与LV-NC组相比,LV-MATN3组表现出明显更高的细胞增殖,迁移,和侵袭(P<0.05),以及肿瘤体积和肿瘤组织中MATN3mRNA表达增加(P<0.05)。相反,sh-MATN3组细胞增殖明显减少,迁移,和入侵,与sh-NC组相比,肿瘤体积和MATN3mRNA水平降低(P<0.05)。
    MATN3在胃癌组织中高表达,与多种病理特征有关,耐药及预后不良。MATN3有可能作为不良预后的诊断标志物,并可能在胃癌细胞的恶性行为中起作用。包括扩散,迁移,和入侵。
    UNASSIGNED: To observe the relationship between the expression of human matricellular protein 3 (MATN3) and the pathological features, drug resistance, and prognosis of gastric cancer based on immunohistochemical method.
    UNASSIGNED: A total of 100 gastric cancer patients treated at the First Affiliated Hospital of Bengbu Medical College from January 2022 to December 2022 were included. MATN3 expression in gastric cancer tissues and paracancerous tissues was assessed by immunohistochemistry. The expression of MATN3 was compared across pathological features. Patients were divided into sensitive and resistant groups based on chemotherapy resistance, and MATN3 expression was compared between these groups. The relationship between MATN3 and recurrence-free survival (RFS) and overall survival (OS) of gastric cancer patients was analyzed using Kaplan-Meier survival curves. Univariate and multifactorial Cox regression analyses were used to analyze the factors affecting the prognosis of gastric cancer patients. Human gastric cancer cells MGC803 were transfected with MATN3. The cells were divided into a high expression group (LV-MATN3 group) and its control group (LV-NC group) and a low expression group (sh-MATN3 group) and its control group (sh-NC group). Cell proliferation was assessed using the CCK8 assay, cell migration and invasion were assessed using the Transwell assay, and MATN3 mRNA expression levels were measured using RT-qPCR. A nude mouse xenograft model was constructed by hypodermic injection of MGC-803 cells transfected with MATN3, and MATN3 mRNA expression levels in tumor tissues were measured using RT-qPCR.
    UNASSIGNED: Immunohistochemical results showed a significantly higher rate of high MATN3 expression in gastric cancer tissues (64.00%, 64/100) compared to adjacent non-cancerous tissues (31.00%, 31/100) (P<0.05). High MATN3 expression was associated with age ≥60 years old, tumor location in the gastric body, tumor size ≥5 cm, lymph node metastasis (N1-N3), histological differentiation (moderate to high), tumor invasion depth (T3-T4), TNM stage (Ⅲ-Ⅳ), distant organ metastasis, recurrence, and mortality (P<0.05). Among patients with chemotherapy resistance, the high MATN3 expression rate was 79.49% (31/39) in the resistant group compared to 54.10% (33/61) in the sensitive group (P<0.05). Follow-up duration ranged from 11 to 22 months, with a 97.00% follow-up rate and 3 cases lost to follow-up. Kaplan-Meier survival curve analysis showed that patients with high MATN3 expression had significantly lower RFS and OS compared to those with low MATN3 expression (RFS: log-rank=17.291, P<0.001; OS: log-rank=21.719, P<0.001). Multivariate Cox analysis identified high MATN3 expression (hazard ratio [HR]=2.291, 95% confidence interval [CI]: 1.268-5.392), tumor location in the gastric body (HR=2.057, 95% CI: 1.441-5.666), lymph node metastasis (N1-N3) (HR=2.011, 95% CI: 1.010-2.274), tumor invasion depth (T3-T4) (H=2.977, 95% CI: 1.032-7.853), TNM stage Ⅲ-Ⅳ (HR=2.008, 95% CI: 1.049-3.902), and distant organ metastasis (HR=2.505, 95% CI: 1.529-5.000) as independent risk factors affecting RFS and OS (P<0.05). Cell and animal experiments demonstrated that compared to the LV-NC group, the LV-MATN3 group exhibited significantly higher cell proliferation, migration, and invasion (P<0.05), as well as increased tumor volume and MATN3 mRNA expression in tumor tissues (P<0.05). Conversely, the sh-MATN3 group showed significantly reduced cell proliferation, migration, and invasion, along with decreased tumor volume and MATN3 mRNA levels compared to the sh-NC group (P<0.05).
    UNASSIGNED: MATN3 is highly expressed in gastric cancer tissues and is associated with various pathological features, drug resistance and poor prognosis. MATN3 holds potential as a diagnostic marker for poor prognosis and may play a role in the malignant behaviors of gastric cancer cells, including proliferation, migration, and invasion.
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  • 文章类型: Journal Article
    本研究旨在分析复旦大学上海癌症中心(FUSCC)的结直肠癌(CRC)患者的病理诊断实践和分子检测技术的变化如何影响临床结局。
    这项回顾性队列研究分析了2008年至2020年在FUSCC诊断的21,141例经病理证实的CRC病例。出于不同的分析目的,将患者分为五组:(1)2014年以来分组分析pT3和pT4分期分级标准的改变对患者生存的影响;(2)全直肠系膜切除术(TME)组,分析直肠系膜完整性评估是否对患者生存有影响;(3)肿瘤沉积(TD)(+)N0vs.TD(+)N1c组分析pN分期变化对TD阳性和区域淋巴结转移(LNM)阴性患者生存率的影响;(4)前2013年以来分组分析缺失错配修复检测过程中的变化对患者生存的影响;(5)未进行RAS/BRAF基因突变检测,分析这些检测对患者生存的影响。患者临床病理参数,包括诊断时的年龄,性别,肿瘤大小,location,分化,粘液亚型,TD,淋巴管浸润,神经周浸润,肿瘤深度,LNM和远处转移,和肿瘤淋巴结转移(TNM)分期,进行组间比较。采用对数秩(logrank)方法进行Kaplan-Meier分析,用于患者总生存期(OS)和无病生存期(DFS)分析。
    在病理报告中,有3个参数变化影响患者结局.首先,pT分期标准的改变导致pT3期与pT4期患者的比例从1:110.9变为1:0.26.与2014年之前收治的患者相比(n=4,754),自2014年以来,观察到pT3和pT4分期之间的预后存在显著差异(n=9,965).其次,自2016年以来,我们开始评估直肠系膜的完整性.因此,91.0%的低位直肠癌患者接受了TME(n=4,111)手术,与部分直肠系膜切除术相比,TME患者的OS明显更好(PME,n=409)。第三,自2017年以来,我们开始将TD(+)LNM(-)作为N1c。结果表明,N1c(n=127)而非N0(n=39)可以改善无LNM和远端转移的患者的预后。在分子测试中,关于错配修复(MMR)/微卫星不稳定性(MSI)状态和RAS/BRAF基因突变检测,分别。自2013年以来,MMR状态测试的标准化大大降低了MMR(dMMR)缺陷患者的比例(从32.5%降至7.4%)。自2013年以来接受MMR状态检测的患者(n=867)的预后明显优于2013年之前的患者(n=1,313)。此外,检测RAS/BRAF基因突变状态(n=5,041)导致更好的DFS而不是OS,I-III期患者(n=16,557)。
    在过去的几十年里,病理报告中元素的更新,以及针对MMR/MSI状态和RAS/BRAF基因突变的标准化测试的开发,显着改善了患者的预后。
    UNASSIGNED: This study aims to analyze how changes in pathological diagnosis practice and molecular detection technology have affected clinical outcomes for colorectal cancer (CRC) patients in Fudan University Shanghai Cancer Center (FUSCC).
    UNASSIGNED: This retrospective cohort study analyzed 21,141 pathologically confirmed CRC cases diagnosed at FUSCC from 2008 to 2020. Patients were divided into five groups for different analytical purposes: (1) the before vs. since 2014 groups to analyze the influence of the changes in the classification criteria of pT3 and pT4 staging on the survival of patients; (2) the partial vs. total mesorectal excision (TME) groups to analyze whether evaluation of completeness of the mesorectum have impact on the survival of patients; (3) the tumor deposit (TD)(+)N0 vs. TD(+)N1c groups to analyze the influence of the changes in the pN staging on the survival of patients with positive TD and negative regional lymph node metastasis (LNM); (4) the before vs. since 2013 groups to analyze the influence of the changes in the testing process of deficient mismatch repair on the survival of patients; and (5) the groups with vs. without RAS/BRAF gene mutation testing to analyze the influence of these testing on the survival of patients. Patients\' clinicopathological parameters, including age at diagnosis, sex, tumor size, location, differentiation, mucinous subtype, TD, lymphovascular invasion, perineural invasion, tumor depth, LNM and distant metastasis, and tumor-node-metastasis (TNM) stage, were compared between groups. Kaplan-Meier analysis with log rank method was performed for patients\' overall survival (OS) and disease-free survival (DFS) analyses.
    UNASSIGNED: In pathological reports, there were three parameter changes that impacted patient outcomes. Firstly, changes in the pT staging criteria led to a shift of the ratio of patients with stage pT3 to stage pT4 from 1: 110.9 to 1: 0.26. In comparison to patients admitted before 2014 (n = 4,754), a significant difference in prognosis between pT3 and pT4 stages was observed since 2014 (n = 9,965). Secondly, we began to evaluate the completeness of the mesorectum since 2016. As a result, 91.0% of patients with low rectal cancer underwent TME (n = 4,111) surgery, and patients with TME had significantly better OS compared with partial mesorectal excision (PME, n = 409). Thirdly, we began to stage TD (+) LNM (-) as N1c since 2017. The results showed that N1c (n = 127) but not N0 (n = 39) can improve the prognosis of patients without LNM and distal metastasis. In molecular testing, there have been three and five iterations of updates regarding mismatch repair (MMR)/microsatellite instability (MSI) status and RAS/BRAF gene mutation detection, respectively. The standardization of MMR status testing has sharply decreased the proportion of deficient MMR (dMMR) patients (from 32.5% to 7.4%) since 2013. The prognosis of patients underwent MMR status testing since 2013 (n = 867) were significantly better than patients before 2013 (n = 1,313). In addition, detection of RAS/BRAF gene mutation status (n = 5,041) resulted in better DFS but not OS, for patients with stage I-III disease (n = 16,557).
    UNASSIGNED: Over the past few decades, updates in elements in pathological reports, as well as the development of standardized tests for MMR/MSI status and RAS/BRAF gene mutations have significantly improved patient outcomes.
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  • 文章类型: Journal Article
    肺浸润性黏液腺癌(IMA)是一种少见的肺癌亚型,易误诊为炎性结节,结核病,肺弥漫性病变,或错构瘤由于缺乏临床特异性。本研究旨在明确IMA的病理和影像学特征,有利于提高诊断和治疗效果。
    一项回顾性研究是在2014年1月至2021年12月的本研究中,通过招募组织病理学诊断为肺IMA的患者进行的。收集临床病理和放射学数据进行分析,以评估IMA的放射学模式以及病理和分子特征。
    总共136名患者被纳入研究,其中58人为男性,78人为女性。患者的平均年龄为63.0±9.7岁。肿瘤分为以下三种病理类型:纯粘液性(76例),仅在显微镜下观察到粘液性细胞;混合粘液性(23例),乳头状,腺泡,和实体瘤细胞有10%以上的黏液细胞。;粘液缺失(29例)以粘液细胞缺失为特征,但仍能检测到10%以上的粘蛋白表达。在基于CT扫描的形态学分类方面,88例(64.7%)被确定为结节型,31(22.8%)为炎症类型,15(11.1%)为质量样类型,和两个(1.5%)作为扩散类型。对于分子特征,IMA患者的甲状腺转录因子-1水平(15%)远低于普通腺癌患者(80%以上).然而,细胞角蛋白20在IMA中(50%)比通常的腺癌(约5%)更常见。K-RAS突变在75%的IMA中普遍存在,与仅15%的普通腺癌形成鲜明对比。与通常的腺癌(约50%)相比,IMA中的表皮生长因子受体突变很少(小于5%)。
    病理和影像学特征丰富了我们对疾病异质性的认识,这将有助于更个性化的诊断和治疗策略。
    UNASSIGNED: Pulmonary invasive mucinous adenocarcinoma (IMA) is a rare subtype of lung cancer which is easily misdiagnosed as inflammatory nodules, tuberculosis, pulmonary diffuse lesions, or hamartomas due to the lack of clinical specificity. This study aims to identify the pathological and imaging characteristics of IMA, which will favor to improve the diagnostic and therapeutic efficacy.
    UNASSIGNED: A retrospective study was conducted by enrolling patients histopathologically diagnosed with pulmonary IMA in the current study between January 2014 and December 2021. The clinical pathological and radiological data were collected for analysis to evaluate the radiological patterns and pathological and molecular characteristics of IMA.
    UNASSIGNED: A total of 136 patients were included in the study, of whom 58 were male and 78 were female. The patients had an average age of 63.0±9.7 years. The tumors were classified into the following three pathological types: pure mucinous (76 cases) featured by only mucinous cells observed under the microscope; mixed mucinous (23 cases) featured as an attached-wall, papillary, acinar, and solid tumor cells with more than 10% mucinous cells.; and mucinous-absent (29 cases) featured with the absence of mucous cells, but still can detect more than 10% of mucin expresses. In terms of the morphological classification based on the CT scans, 88 (64.7%) cases were identified as the nodular type, 31 (22.8%) as the inflammatory type, 15 (11.1%) as the mass-like type, and two (1.5%) as the diffuse type. For the molecular features, patients afflicted with IMA showed much lower levels of thyroid transcription factor-1 (15%) than those with usual adenocarcinoma (over 80%). However, cytokeratin 20 was more common in IMA (50%) than the usual adenocarcinoma (about 5%). The K-RAS mutation was prevalent in 75% of IMA, which contrasted sharply to its occurrence in a mere 15% of the usual adenocarcinoma. Epidermal growth factor receptor mutations were rarer in IMA (less than 5%) than the usual adenocarcinoma (about 50%).
    UNASSIGNED: The pathological and imaging features enrich our understanding of the disease\'s heterogeneity, which will contribute to more personalized diagnostic and therapeutic strategies.
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  • 文章类型: Case Reports
    背景:异位胸膜胸腺瘤和其他胸部肿瘤之间的影像学诊断复杂性很大,同时发生的T细胞淋巴细胞增多和骨转移的情况极为罕见。
    方法:一名51岁女性因呼吸困难和胸痛入院。影像学检查,她被发现左侧弥漫性和结节性胸膜增厚,左肺塌陷,第二胸椎受压。所有病灶18F-FDGPET/CT检查均显示明显的18F-FDG摄取。此外,她的外周血中有T细胞淋巴细胞增多,淋巴结,还有骨髓.排除恶性胸膜间皮瘤(MPM)后,肺癌胸膜转移,和T细胞淋巴瘤,明确诊断为异位胸膜胸腺瘤伴T细胞淋巴细胞增多和骨转移.
    结论:医师需要扩大对异位胸膜胸腺瘤影像学特征的认识。患有T细胞淋巴细胞增多症的病例可能表现出增加的侵袭性并易于发生骨转移。
    BACKGROUND: The diagnostic complexities that arise in radiographic distinction between ectopic pleural thymoma and other thoracic neoplasms are substantial, with instances of co-occurring T-cell lymphocytosis and osseous metastasis being exceedingly rare.
    METHODS: A 51-year-old woman was admitted to our hospital with dyspnea and chest pain. Upon imaging examination, she was found to have diffuse and nodular pleural thickening on the left side, collapse of the left lung and a compression in the second thoracic vertebrae. All lesions showed significant 18F-FDG uptake on 18F-FDG PET/CT examination. Furthermore, she exhibited T-cell lymphocytosis in her peripheral blood, lymph nodes, and bone marrow. After ruling out malignant pleural mesothelioma (MPM), lung cancer with pleural metastasis, and T-cell lymphoma, the definitive diagnosis asserted was ectopic pleural thymoma with T-cell lymphocytosis and bone metastasis.
    CONCLUSIONS: Physicians need to expand their knowledge of the imaging features of ectopic pleural thymoma. Cases with T-cell lymphocytosis may exhibit increased aggressiveness and prone to bone metastasis.
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  • 文章类型: Journal Article
    背景:自身免疫性肠病(AIE)是一种罕见的疾病,其诊断和长期预后仍然具有挑战性,特别是成人AIE患者。
    目的:提高对本病诊断和预后的整体认识。
    方法:我们回顾性分析了临床,2011年至2023年期间,我们三级医疗中心的16例成人AIE患者的内镜和组织病理学特征及预后,这些患者的诊断基于2007年的诊断标准.
    结果:AIE患者的腹泻特征为分泌性腹泻。常见的内镜表现为水肿,十二指肠和回肠的绒毛钝化和粘膜充血。绒毛钝化(100%),深隐窝淋巴细胞浸润(67%),凋亡体(50%),在十二指肠活检中观察到轻度上皮内淋巴细胞增多(69%)。此外,还有其他显著的异常,包括杯状细胞减少或缺失(十二指肠94%,回肠62%),潘氏细胞减少或缺失(十二指肠94%,回肠69%)和中性粒细胞浸润(十二指肠100%,回肠69%)。我们的患者也符合2018年的诊断标准,但由于无法检测到抗肠细胞抗体,因此不符合2022年的诊断标准。所有患者均接受糖皮质激素治疗作为初始用药,其中14/16例患者在5(IQR:3-20)天内达到临床缓解。对9例具有类固醇依赖指征的患者使用免疫抑制剂(6/9),类固醇难治性状态(2/9),或强化维持药物治疗(1/9)。在20.5个月的随访中,2例死于多器官功能衰竭,1例诊断为非霍奇金淋巴瘤。累计无复发生存率为62.5%,6个月时分别为55.6%和37.0%,12个月和48个月,分别。
    结论:某些组织病理学发现,包括肠道活检中杯状细胞和潘氏细胞的减少或消失,可能是成人AIE的潜在诊断标准。尽管使用皮质类固醇和免疫抑制剂,但长期预后仍不令人满意。这凸显了对早期诊断和新型药物的需求。
    BACKGROUND: Autoimmune enteropathy (AIE) is a rare disease whose diagnosis and long-term prognosis remain challenging, especially for adult AIE patients.
    OBJECTIVE: To improve overall understanding of this disease\'s diagnosis and prognosis.
    METHODS: We retrospectively analyzed the clinical, endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023, whose diagnosis was based on the 2007 diagnostic criteria.
    RESULTS: Diarrhea in AIE patients was characterized by secretory diarrhea. The common endoscopic manifestations were edema, villous blunting and mucosal hyperemia in the duodenum and ileum. Villous blunting (100%), deep crypt lymphocytic infiltration (67%), apoptotic bodies (50%), and mild intraepithelial lymphocytosis (69%) were observed in the duodenal biopsies. Moreover, there were other remarkable abnormalities, including reduced or absent goblet cells (duodenum 94%, ileum 62%), reduced or absent Paneth cells (duodenum 94%, ileum 69%) and neutrophil infiltration (duodenum 100%, ileum 69%). Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies. All patients received glucocorticoid therapy as the initial medication, of which 14/16 patients achieved a clinical response in 5 (IQR: 3-20) days. Immunosuppressants were administered to 9 patients with indications of steroid dependence (6/9), steroid refractory status (2/9), or intensified maintenance medication (1/9). During the median of 20.5 months of follow-up, 2 patients died from multiple organ failure, and 1 was diagnosed with non-Hodgkin\'s lymphoma. The cumulative relapse-free survival rates were 62.5%, 55.6% and 37.0% at 6 months, 12 months and 48 months, respectively.
    CONCLUSIONS: Certain histopathological findings, including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies, might be potential diagnostic criteria for adult AIE. The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications, which highlights the need for early diagnosis and novel medications.
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  • 文章类型: Journal Article
    背景:结直肠癌(CRC)是全球第三大常见癌症,也是癌症相关死亡的第二大常见原因。间充质-上皮转化因子(MET)基因参与多种肿瘤生物学,并显示出在肿瘤治疗中的药理操作的临床潜力。在CRC中已经报道了MET扩增,但是数据非常有限。研究CRC中MET的病理学价值可能为未来的临床实践提供新的治疗和遗传筛查选择。
    目的:确定MET扩增在CRC中的病理学意义,并提出可行的筛查策略。
    方法:选择在中国医学科学院肿瘤医院接受手术切除治疗的205例初诊CRC患者。所有患者均无RAS/RAF突变或微卫星不稳定性高。使用荧光原位杂交(FISH)和免疫组织化学(IHC)分析MET扩增和c-MET蛋白表达,分别。使用卡方检验检测MET畸变与病理特征之间的相关性。使用Kaplan-Meier方法和对数秩检验检测两年随访期间的无进展生存期(PFS)。使用单向方差分析比较METFISH和IHC的结果。
    结果:在14.4%的病例中观察到多体性引起的MET扩增,未检测到局灶性MET扩增。多体分裂诱导的MET扩增与较高的淋巴结转移(LNM)频率(P<0.001)和较高的肿瘤出芽分级(P=0.02)相关。在生存分析中,在首次诊断后的2年随访中,扩增和非扩增MET患者之间存在显著差异(P=0.001).C-MET评分为0,1+,2+,在1.4%中观察到3+,24.9%,54.7%,和19.0%的肿瘤,分别。C-MET过表达与LNM发生频率相关(P=0.002),但不同蛋白水平患者的PFS差异无统计学意义。就METFISH和IHC结果之间的一致性而言,MET拷贝数显示c-METIHC0/1+(3.35±0.18),2+(3.29±0.11)和3+(3.58±0.22)组,MET与CEP7的比值在三组中没有差异(1.09±0.02,1.10±0.01和1.09±0.03)。
    结论:在CRC中,局灶性MET扩增是罕见事件.多体分体引起的MET扩增与不良病理特征和不良预后相关。IHC是用于MET扩增的差的筛选工具。
    BACKGROUND: Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer-related mortality worldwide. Mesenchymal-epithelial transition factor (MET) gene participates in multiple tumor biology and shows clinical potential for pharmacological manipulation in tumor treatment. MET amplification has been reported in CRC, but data are very limited. Investigating pathological values of MET in CRC may provide new therapeutic and genetic screening options in future clinical practice.
    OBJECTIVE: To determine the pathological significance of MET amplification in CRC and to propose a feasible screening strategy.
    METHODS: A number of 205 newly diagnosed CRC patients undergoing surgical resection without any preoperative therapy at Shenzhen Cancer Hospital of Chinese Academy of Medical Sciences were recruited. All patients were without RAS/RAF mutation or microsatellite instability-high. MET amplification and c-MET protein expression were analyzed using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), respectively. Correlations between MET aberration and pathological features were detected using the chi-squared test. Progression free survival (PFS) during the two-year follow-up was detected using the Kaplan-Meier method and log rank test. The results of MET FISH and IHC were compared using one-way ANOVA.
    RESULTS: Polysomy-induced MET amplification was observed in 14.4% of cases, and focal MET amplification was not detected. Polysomy-induced MET amplification was associated with a higher frequency of lymph node metastasis (LNM) (P < 0.001) and higher tumor budding grade (P = 0.02). In the survival analysis, significant difference was detected between patients with amplified- and non-amplified MET in a two-year follow-up after the first diagnosis (P = 0.001). C-MET scores of 0, 1+, 2+, and 3+ were observed in 1.4%, 24.9%, 54.7%, and 19.0% of tumors, respectively. C-MET overexpression correlated with higher frequency of LNM (P = 0.002), but no significant difference of PFS was detected between patients with different protein levels. In terms of concordance between MET FISH and IHC results, MET copy number showed no difference in c-MET IHC 0/1+ (3.35 ± 0.18), 2+ (3.29 ± 0.11) and 3+ (3.58 ± 0.22) cohorts, and the MET-to-CEP7 ratio showed no difference in three groups (1.09 ± 0.02, 1.10 ± 0.01, and 1.09 ± 0.03).
    CONCLUSIONS: In CRC, focal MET amplification was a rare event. Polysomy-induced MET amplification correlated with adverse pathological characteristics and poor prognosis. IHC was a poor screening tool for MET amplification.
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  • 文章类型: Journal Article
    放化疗(CRT)和放疗(RT)已作为抗癌治疗和新辅助疗法,用于治疗包括结直肠癌(CRC)在内的多模态直肠癌。然而,伴随的放射诱导的结直肠纤维化(RICF)已导致患者结直肠粘膜的慢性毒性和狭窄.具有独特的双向免疫调节和抗纤维化作用的间充质干细胞/基质细胞(MSC)已被认为是用于包括肠道疾病在内的再生目的的出色来源。在这里,我们的目标是验证基于MSC的细胞疗法从病理特征中缓解RICF的可行性和变异,以及对RICF大鼠转录组特征的潜在影响.出于目的,我们利用我们建立良好的RICFSprague-Dawley(SD)大鼠进行辐射五周,并连续腹膜内注射两种不同的MSCs进行治疗,包括来源于成人脂肪组织的MSCs(AD-MSCs)和围产期脐带MSCs(UC-MSCs)。一方面,通过多种指标评估AD-MSCs和UC-MSCs的疗效,包括体重变化,病理检测(例如,H&E染色,Masson染色,EVG染色,IF染色,和IHC染色),和促炎和纤维化因子的表达。另一方面,我们转向RNA测序(RNA-SEQ)和多方面的生物信息学分析(例如,GOBP,维恩地图,KEGG,和GSEA),以比较AD-MSC和UC-MSC治疗对基因表达谱和遗传变异的影响。连续施用AD-MSC和UC-MSC后,RICF大鼠在组织病理学特征方面表现出相当的缓解,并显着抑制了多种促炎和纤维化因子的表达。同时,与RICF大鼠相比,两种MSC治疗后的RICF大鼠均显示出不同基因表达和体细胞突变的减少和变化。总的来说,我们的数据表明AD-MSCs和UC-MSCs对SD大鼠RICF的治疗效果相当,以及基因表达谱的保守和基因突变的不同变化。我们的研究结果表明,MSC输注在治疗和转录组水平上对RICF的监督具有多方面的影响。这将为将来基于MSC的方案的进一步评估和开发提供新的参考。
    Chemoradiotherapy (CRT) and radiotherapy (RT) have served as anticancer treatments and neoadjuvant therapies for conquering multimodal rectal cancers including colorectal carcinoma (CRC), yet the concomitant radiation-induced colorectal fibrosis (RICF) has caused chronic toxicity and stenosis in the colorectal mucosa of patients. Mesenchymal stem/stromal cells (MSCs) with unique bidirectional immunoregulation and anti-fibrotic effect have been recognized as splendid sources for regenerative purposes including intestinal diseases. Herein, we are aiming to verify the feasibility and variations of MSC-based cytotherapy for the remission of RICF from the pathological features and the potential impact upon the transcriptomic signatures of RICF rats. For the purpose, we utilized our well-established RICF Sprague-Dawley (SD) rats by radiation for five weeks, and conducted consecutive intraperitoneal injection of two distinct MSCs for treatment, including MSCs derived from adult adipose tissue (AD-MSCs) and perinatal umbilical cord (UC-MSCs). On the one hand, the efficacy of AD-MSCs and UC-MSCs was assessed by diverse indicators, including weight change, pathological detections (e.g., H&E staining, Masson staining, EVG staining, IF staining, and IHC staining), and proinflammatory and fibrotic factor expression. On the other hand, we turned to RNA-sequencing (RNA-SEQ) and multifaceted bioinformatics analyses (e.g., GOBP, Venn Map, KEGG, and GSEA) to compare the impact of AD-MSC and UC-MSC treatment upon the gene expression profiling and genetic variations. RICF rats after consecutive AD-MSC and UC-MSC administration revealed comparable remission in histopathogenic features and significant suppression of diverse proinflammatory and fibrotic factors expression. Meanwhile, RICF rats after both MSC treatment revealed decrease and variations in the alterations in diverse gene expression and somatic mutations compared to RICF rats. Collectively, our data indicated the comparable therapeutic effect of AD-MSCs and UC-MSCs upon RICF in SD rats, together with the conservations in gene expression profiling and the diverse variations in genetic mutations. Our findings indicated the multifaceted impact of MSC infusion for the supervision of RICF both at the therapeutic and transcriptomic levels, which would provide novel references for the further evaluation and development of MSC-based regimens in future.
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  • 文章类型: Journal Article
    背景:腹膜假粘液瘤(PMP)是一种罕见的临床恶性综合征,它的稀有性导致缺乏病理学研究。本研究旨在定量分析HE染色的病理图像(PIs),并开发了一种将数字病理参数与临床信息相结合的新预测模型。
    方法:92例有完整临床病理资料的PMP患者,包括在内。QuPath用于组织的PI定量特征分析,cell-,和核级。总生存期(OS)与一般临床病理特征之间的相关性,并对PI特征进行了分析。根据独立的预后因素建立列线图并进行评估。
    结果:在92例PMP患者中,女性34人(37.0%),男性58人(63.0%),年龄中位数为57岁(范围:31-76)。共获得449张HE染色图像进行QuPath分析。从三个层次提取了40个病理参数。Kaplan-Meier生存分析显示8个临床病理特征和20个PI特征与OS显著相关(p<0.05)。采用偏最小二乘回归对多重共线性特征进行筛选,并合成4个新特征。多变量生存分析确定了以下五个独立的预后因素:术前CA199,细胞减记术的完整性,组织病理学类型,组织水平的成分之一,和肿瘤核圆形度方差。建立了具有内部验证C指数0.795和校准图的列线图,表明预测性能得到了改善。
    结论:HE染色的PIs定量分析可以提取PMP的新预后信息。由五个独立的预测者建立的列线图是第一个将数字病理信息与临床数据相结合以改善临床结果预测的模型。
    BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare clinical malignant syndrome, and its rarity causes a lack of pathology research. This study aims to quantitatively analyze HE-stained pathological images (PIs), and develop a new predictive model integrating digital pathological parameters with clinical information.
    METHODS: Ninety-two PMP patients with complete clinic-pathological information, were included. QuPath was used for PIs quantitative feature analysis at tissue-, cell-, and nucleus-level. The correlations between overall survival (OS) and general clinicopathological characteristics, and PIs features were analyzed. A nomogram was established based on independent prognostic factors and evaluated.
    RESULTS: Among the 92 PMP patients, there were 34 (37.0%) females and 58 (63.0%) males, with a median age of 57 (range: 31-76). A total of 449 HE stained images were obtained for QuPath analysis, which extracted 40 pathological parameters at three levels. Kaplan-Meier survival analysis revealed eight clinicopathological characteristics and 20 PIs features significantly associated with OS (p < 0.05). Partial least squares regression was used to screen the multicollinearity features and synthesize four new features. Multivariate survival analysis identified the following five independent prognostic factors: preoperative CA199, completeness of cytoreduction, histopathological type, component one at tissue-level, and tumor nuclei circularity variance. A nomogram was established with internal validation C-index 0.795 and calibration plots indicating improved prediction performance.
    CONCLUSIONS: The quantitative analysis of HE-stained PIs could extract the new prognostic information on PMP. A nomogram established by five independent prognosticators is the first model integrating digital pathological information with clinical data for improved clinical outcome prediction.
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  • 文章类型: Journal Article
    背景先天性/婴儿纤维肉瘤是一种罕见的软组织肿瘤,在生命早期出现。在大型软组织肿块的鉴别诊断中,尤其是在婴儿期的四肢中,应考虑到这一点。这些肿瘤在出生时经常被误诊为血管瘤。组织学上,它们可以类似于它们的成年对应物,并且它们的特征在于导致ETV6-NTRK3基因融合的染色体易位t(12;15)(p13;q25)。目的回顾性回顾经组织病理学证实的先天性/婴儿纤维肉瘤的MRI特征,提供了我们自己的机构经验,并支持有关该疾病的有限放射学文献。材料和方法我们的患者名单是在6月1日期间回顾我们的放射学和病理学数据库后获得的,2007年5月31日,2017年(10年)在费萨尔国王专科医院和研究中心,利雅得.在我们的MRI检查数据库中用于搜索的短语是:先天性婴儿纤维肉瘤,婴儿纤维肉瘤,幼年纤维肉瘤,软组织肉瘤,恶性软组织肿块,肉瘤软组织肿块,纤维肉瘤,梭形细胞肉瘤,肌瘤肉瘤.结果在研究期间,在我们的数据库和图片存档和通信系统(PACS)中,182例患者的放射学报告中提到了这个词(纤维肉瘤).只有4例经组织病理学证实为先天性/婴儿纤维肉瘤,并完成了自己的MR检查-其中3例是原发性/新发病例。年龄在0天至5个月之间的男性(中位年龄:5个月)。第四例是一名女性,在一个月大时有第一次出现病史,并经组织病理学检查证实,但当时没有可用的影像学检查;然而,同一患者的肿瘤复发年龄为4岁,有MR成像和病理样本.结论先天性婴儿纤维肉瘤是一种少见的无特异性MRI表现。然而,应始终将其视为具有攻击行为的先天性软组织肿块的鉴别诊断的一部分。
    Background Congenital/infantile fibrosarcoma is a rare soft tissue tumor presented in early age of life. It should be considered in the differential diagnosis of the large soft tissue masses especially in the extremities at the age of infancy. These tumors frequently are misdiagnosed at birth as hemangioma. Histologically, they can resemble their adult counterparts and they are characterized by the chromosomal translocation t(12;15) (p13;q25) resulting in the ETV6-NTRK3 gene fusion. Objective A retrospective review of the MRI features of histopathology-proven congenital/infantile fibrosarcoma provides our own institutional experience and supports the limited radiology literature written about this disease. Material and method The list of our patients is obtained after reviewing our radiology and pathology database in the period between June 1st, 2007 and May 31st, 2017 (10 years) at King Faisal Specialist Hospital & Research Center, Riyadh. Phrases used to search in our MRI examinations database are: congenital infantile fibrosarcoma, infantile fibrosarcoma, juvenile fibrosarcoma, soft tissue sarcoma, malignant soft tissue mass, sarcomatous soft tissue mass, fibrosarcoma, spindle cell sarcoma, myomatous sarcoma. Result In our database and picture archiving and communication system (PACS) during the period of the study, the word (fibrosarcoma) was mentioned in the radiology report of 182 patients. Only four cases were histopathologically proven to be a congenital/infantile fibrosarcoma and had completed their own MR exams - three of them were primary/new cases, males with an age range between 0 days and 5 months (median age: 5 months). The fourth case was a female with a history of 1st presentation at the age of one month and proved by histopathology examination but there was no available imaging at that time; however, tumor recurrence in the same patient was at the age of 4 years with available MR imaging and pathology sample. Conclusion Congenital infantile fibrosarcoma is a rare entity that has no specific MRI findings. However, it should be always considered as part of the differential diagnosis of congenital soft tissue masses with aggressive behavior.
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  • 文章类型: Meta-Analysis
    背景:肿瘤出芽(TB)是结直肠癌的负面预后因素;然而,其对直肠癌患者新辅助治疗后的预后影响尚不清楚.本研究旨在评估直肠癌患者新辅助治疗后TB对预后的影响以及TB与其他病理特征之间的相关性。
    方法:对PubMed的全面搜索,Embase,科克伦,Scopus,CNKI,万方,和ClinicalKey数据库从数据库开始到2023年1月进行了新辅助治疗后直肠癌中TB预后的研究,最终纳入的文献使用预定义的标准确定.对研究的质量评估包括,从他们中提取一般和预后信息,并逐步进行荟萃分析。
    结果:共纳入11项研究,meta分析结果显示,高级别肿瘤出芽(TB-1)增加了5年无病生存率低的风险(HR=1.75,95%CI1.38-2.22,P<0.00001),5年总生存率(HR=1.77,95%CI1.21-2.59,P=0.003),局部复发(OR=4.15,95%CI1.47-11.75,P=0.007),直肠癌患者新辅助治疗后发生远处转移(OR=5.36,95%CI2.51~11.44,P<0.0001)。TB-1与分化差和淋巴管显著相关,神经周,和静脉侵入。
    结论:直肠癌新辅助治疗后,肿瘤出芽与不良预后和不良病理特征显著相关。我们期待更多的高品质,未来的前瞻性研究证实了我们的发现。
    背景:PROSPEROCRD42022377564.
    Tumor budding (TB) is a negative prognostic factor in colorectal cancer; however, its prognostic impact following neoadjuvant therapy for patients with rectal cancer remains unclear. This study aims to assess the prognostic impact of TB and the correlation between TB and other pathological features in patients with rectal cancer after neoadjuvant therapy.
    A comprehensive search of PubMed, Embase, Cochrane, Scopus, CNKI, Wanfang, and ClinicalKey databases was conducted for studies on the prognosis of TB in rectal cancer after neoadjuvant therapy from the inception of the databases to January 2023, and the final literature included was determined using predefined criteria. Quality assessment of the studies included, extraction of general and prognostic information from them, and meta-analyses were carried out progressively.
    A total of 11 studies were included, and the results of the meta-analysis showed that high-grade tumor budding (TB-1) increased the risk of poor 5-year disease-free survival (HR = 1.75, 95% CI 1.38-2.22, P < 0.00001), 5-year overall survival (HR = 1.77, 95% CI 1.21-2.59, P = 0.003), local recurrence (OR = 4.15, 95% CI 1.47-11.75, P = 0.007), and distant metastasis (OR = 5.36, 95% CI 2.51-11.44, P < 0.0001) in patients with rectal cancer after neoadjuvant therapy. TB-1 was significantly associated with poor differentiation and lymphatic, perineural, and venous invasion.
    Tumor budding is significantly correlated with unfavorable prognosis and poor pathological characteristics following neoadjuvant therapy for rectal cancer. We anticipate more high-quality, prospective studies in the future to confirm our findings.
    PROSPERO CRD42022377564.
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