复合性小细胞肺癌临床病理学特征及预后分析

探讨复合性小细胞肺癌（combined small cell lung cancer,CSCLC）临床病理学特征及其与预后的关系。方法:收集天津医科大学附属肿瘤医院2006年1月至2008年12月入院治疗行根治性手术切除并经病理证实为CSCLC病例44例,重新审阅肿物病理切片,回顾性分析其临床及病理学特征,Kaplan-Meier法计算生存率并描绘生存曲线,Cox风险回归模型分析影响总生存期（overall survival,OS）及无瘤生存期（disease-free survival,DFS）的独立因素。结果:全组CSCLC患者OS为6～57个月,中位OS为20个月;DFS为3～57个月,平均14.5个月。Kaplan-Meier生存曲线显示,女性DFS长于男性,肿瘤位置、小细胞癌复合成分病理类型对OS有影响（P<0.05）。多因素分析显示,肿瘤位于左肺或右肺及复合成分病理类型为影响患者OS的危险因素,未发现影响患者术后DFS的危险因素。结论:CSCLC属于一种特殊类型的肺混合性癌,治疗应采取以手术为主的综合治疗方案,判定其复合成分的病理类型对于临床上判断预后具有重要的意义。      

283例胰腺癌根治术后患者临床资料和生存分析

目的：探讨胰腺癌根治术后患者临床病理特征与预后的关系。方法回顾性分析行胰腺癌根治手术治疗的、病理确诊为胰腺导管腺癌的患者283例,分析其临床病理特征及生存情况。结果283例患者的中位无瘤生存期（median disease free survival,mDFS）为7．9月,中位总生存期（median overall survival,mOS）为15．0月。多因素分析显示,肿瘤手术切缘状态以及肿瘤TNM分期是影响胰腺癌根治术后患者DFS的独立预后因素（均P＜0.05）,肿瘤淋巴结状态以及肿瘤TNM分期是影响胰腺癌根治术后患者OS的独立预后因素（均P＜0．05）。结论对于胰腺癌根治术后患者,手术切缘状态和TNM分期是影响DFS的独立风险因素,TNM分期和肿瘤淋巴结状态是影响OS的独立风险因素。     

共突变基因与晚期非小细胞肺癌靶向治疗预后生存的相关性分析

目的:进一步验证晚期表皮生长因子受体（epidermal growth factor receptor,EGFR）突变非小细胞肺癌(non-small cell lung cancer,NSCLC)靶向治疗预后生存情况,探讨共突变基因与患者预后生存的相关性。方法:回顾性分析2016年01月至2019年12月我院经病理确诊为晚期NSCLC,二代测序（next-generation sequencing,NGS）为EGFR突变阳性,且使用表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKI）一代药物作为一线治疗的102例患者的病历和随访资料。收集其临床病理特征、治疗前的检验结果、基因检测报告、共突变基因和随访信息。采用Cox回归模型分析共突变基因与无疾病进展生存期（progression-free survival,PFS）的相关性。通过基因表达谱数据动态分析（Gene Expression Profiling Interactive Analysis,GEPIA）公共数据库分析磷脂酞肌醇-3-激酶催化亚单位α基因（phosphoinositide-3-kinase catalytic alpha polypeptide gene,PIK3CA）、人类表皮生长因子受体2（human epidermal growth factor receptor 2,HER-2）、间质表皮转化因子（mesenchymal-epithelial transition factor,MET）三种共突变基因与肺癌总生存期（overall survival,OS）和无病生存期（disease-free survival,DFS）的相关性。结果:102例一线靶向治疗的晚期NSCLC患者中位PFS为10个月。单因素分析表明,EGFR突变合并PIK3CA突变的患者一线靶向治疗的中位PFS为8个月,不合并PIK3CA突变患者的中位PFS为11个月,差异有统计学意义（P=0.037）;EGFR突变合并T790M突变患者的中位PFS为6个月,不合并T790M突变患者中位PFS为10个月,差异有统计学意义（P=0.043）;EGFR突变合并HER-2扩增的患者中位PFS为7个月,不合并HER-2扩增的患者中位PFS为10个月,差异有统计学意义（P=0.048）;EGFR突变合并MET扩增的患者中位PFS为3个月,不合并MET扩增的患者中位PFS为10个月,差异有统计学意义（P=0.001）。多因素分析显示,合并PIK3CA突变（HR=0.536,95%CI:0.302~0.951,P=0.033）、HER-2扩增（HR=0.359,95%CI:0.142~0.909,P=0.031）、MET扩增（HR=0.139,95%CI:0.042~0.464,P=0.001）是PFS的独立预后因素。PIK3CA基因与晚期NSCLC的DFS有相关性（P<0.05）。结论:晚期NSCLC靶向治疗前合并PIK3CA突变、HER-2扩增、MET扩增是患者PFS的独立影响因素。     

非小细胞肺癌组织MET和EGFR基因扩增与预后相关性分析

目的：探讨非小细胞肺癌（non-smfllleelllungcancer,NSCLC）患者中肝细胞生长因子受体（MET）基因和表皮生长因子受体（epidermalgrowthfactorreceptor,EGFR）基因扩增与临床病理特征及预后的关系。方法：回顾分析唐山市协和医院（48例）和唐山市人民医院（109例）2001—01—2007—01手术切除的NSCLC石蜡包埋标本157例。应用荧光原位杂交（fluorescenceinsituhybridization,FISH）检测NSCLCMET、EGFR基因扩增情况,并结合临床病理资料进行统计分析。应用SPSS16．0进行统计分析,Kaplan-Meier模型分析中住生存期（overallsurvival,0S）,Log—rank检验比较生存曲线,多因素分析采用Cox回归模型。结果：157例NSCLC患者标本中,EGFR基因扩增70例（44．6％）。EGFR基因扩增与年龄、性别、吸烟状态、组织类型和TNM分期无关,P〉0．05。157例NSCLC患者标本中,MET基因扩增25例（15．9％）。EGFR扩增患者MET扩增率为22．9％,高于无EGFR扩增患者MET扩增率10．3％,P=0．033。MET基因扩增与年龄、性别、吸烟状态、组织类型和TNM分期无关,P〉0．05。Kaplan-Meier生存分析显示,I＋Ⅱ期中位生存期为51个月,明显高于Ⅲ＋Ⅳ期中位生存期29个月,P=0．001。EGFRFISH阳性患者中位0s为33个月与EGFRFISH阴性患者中位0s39个月比较,差异无统计学意义,P=0．495。METFISH阳性患者中位0S为29个月,低于METFISH阴性患者37个月,P=0．044。患者0s与病理类型、年龄、性别和吸烟状态无相关性,P〉0．05。多因素分析显示,临床分期、MET基因扩增与OS有关（相对危险度为12．573、6．892,P值分别为0．015、0．018）。结论：临床Ⅲ＋Ⅳ期和MET基因扩增NSCLC患者预后不良,EGFR基因扩增与NSCLC患者预后无关。     

肉瘤样肝癌24例临床分析

  目的  通过分析各分期肉瘤样肝癌（sarcomatoid hepatocellular carcinoma，SHC）的临床资料、治疗方法及预后，提高临床医生对肉瘤样肝癌的认识。  方法  回顾性分析郑州大学第一附属医院2015年1月至2019年12月病理确诊为SHC 24例患者临床资料并随访，男性16例，女性8例。中位发病年龄55岁。  结果  临床表现以腹痛、发热为主，肝炎病毒感染者占66.7%，肝硬化者占79.2%。Ⅲ~Ⅳ期占87.5%。平均肿瘤长径6.27 cm。1例行肝移植，8例行手术为主治疗，3例仅进行局部治疗，余进行对症支持、化疗、靶向或联合免疫治疗。入院CT或MRI均有异常表现，活检或术后病理均符合SHC。随访1~39.7个月，中位随访时间4.8个月，术后患者中位总生存期（overall survival，OS）为4.7个月，中位无病生存期（disease-free survival，DFS）为2.3个月。Ⅲ~Ⅳ期患者中位OS为4.8个月。  结论  对于Ⅰ期肉瘤样肝癌患者，治疗以外科切除为主，术后给予辅助治疗可使患者受益。对于Ⅲ~Ⅳ期肉瘤样肝癌患者，手术获益局限，可行全身化疗、口服靶向药、局部治疗等减轻肿瘤负荷。但无论分期及治疗措施如何，SHC患者普遍预后差。化疗加靶向药物联合免疫治疗可能成为晚期SHC的治疗新方向。      

74例皮肤黑色素瘤的预后及影响因素分析

目的 探讨皮肤恶性黑色素瘤的临床病理特征及预后相关因素。方法 回顾性分析南京鼓楼医院2010年1月至2016年6月收治的74例皮肤黑色素瘤患者的临床病理资料。所有入组患者均接受手术治疗,术后辅助治疗分为联合免疫治疗和未联合免疫治疗,免疫治疗方法包括细胞因子治疗和过继性免疫细胞回输疗法,未联合免疫治疗者包括术后未治疗的以及术后仅行辅助放疗或辅助化疗的患者。根据随访资料分析预后情况,并采用Cox比例风险回归模型分析影响预后的因素。结果 全组患者的中位生存期（OS）和无病生存期（DFS）分别为 32.0个月（95％CI： 20.2～43.8个月）和23.0个月（95％CI： 16.4～29.6个月）。Ⅲ期患者术后联合免疫治疗较未联合免疫治疗中位OS延长（38.0个月 vs. 10.0个月,P=0.002）。多因素分析显示,年龄、分期、淋巴结转移、原发灶溃疡和肿瘤Breslow厚度是影响皮肤黑色素瘤OS的独立因子,分期、淋巴结转移、原发灶溃疡和肿瘤Breslow厚度是影响DFS的独立因子。结论 年龄、分期、淋巴结转移、肿瘤Breslow厚度和原发灶溃疡均与皮肤恶性黑色素瘤患者的预后密切相关。Ⅲ期患者术后联合免疫治疗可延长OS。     

全身免疫炎症指数（SII）对胶质瘤患者临床预后的影响及与p53突变的关系

目的:探讨全身免疫炎症指数（SII）对胶质瘤患者临床预后的影响及与p53突变的关系。方法:收集2006年8月至2015年11月于我院脑外科行手术治疗的80例神经胶质瘤患者。应用ROC曲线确定SII最佳临床分界值,并依此分组。采用Kaplan-Meier和Log-rank法分析两组患者术后生存情况。COX比例风险模型分析临床预后因素。应用免疫组织化学方法检测p53基因突变情况。结果:SII是神经胶质瘤的独立预后因素,最佳临床分界值为500×109/L。低SII组术后中位无病生存时间（disease free survival,DFS)和中位总生存时间（overall survival,OS)分别为43.85个月和56.69个月,而高SII组术后中位DFS和中位OS分别为29.10个月和45.10个月,两组DFS和OS比较,差异具有统计学意义（P＜0.05）。经单因素和多因素分析,年龄、手术情况、WHO分级、SII、p53突变是神经胶质瘤的独立预后因素。未发生p53突变的低SII组神经胶质瘤患者预后好于其他情况。结论:SII是神经胶质瘤的独立预后因素,具有简单方便、可重复性强、非侵袭性等特点,可用来预测神经胶质瘤患者的预后,未发生p53突变的低SII组神经胶质瘤患者预后较好。     

接头蛋白DOK2在结直肠癌中的表达及临床病理学意义

目的:研究接头蛋白DOK2在结直肠癌中的表达及其临床病理学意义。方法:免疫组化检测87例结直肠癌组织中DOK2的表达,并对结直肠癌患者进行生存分析。结果:DOK2在63例（72%）结直肠癌组织中表达阴性,在正常组织中表达阳性。DOK2表达丢失与肿瘤分化程度（P=0.001）和复发（P=0.048）之间有显著相关性。COX回归分析显示,DOK2表达丢失是结直肠癌患者总体生存率（overall survival,OS）（P=0.001）和无复发生存率（recurrence-free survival,RFS）（P=0.006）的独立影响因素。Kaplan-Meier法生存分析表明,与DOK2表达阳性的患者相比,DOK2表达阴性的患者中位生存时间显著缩短（46个月vs 53个月,P＜0.001）,无复发中位生存时间也显著缩短（36个月 vs 49个月,P＜0.001）。结论:接头蛋白DOK2是结直肠癌患者预后的独立影响因素。     

DNA损伤同源重组修复相关蛋白在软组织平滑肌肉瘤中的表达及其预后意义

摘 要：［目的］ 探讨DNA损伤同源重组修复相关蛋白在软组织平滑肌肉瘤 (leiomyosarcoma,LMS) 中的表达及其预后意义。［方法］ 采用免疫组化SP法检测61例LMS中RAD51 重组酶 (RAD51)、 RAD52同源性DNA修复蛋白(RAD52)、ATM丝氨酸／苏氨酸(ATM)及ATR丝氨酸／苏氨酸(ATR)的表达。［结果］ 61例LMS患者的1年、5年和10年生存率分别为87％、46%和19%;中位生存期（overall survival,OS）为44.7个月,中位无病生存期(disease-free survival,DFS)为30.3个月,中位无进展生存期(progress-free survival,PFS)为17.0个月。LMS中RAD51、RAD52、ATM及ATR的阳性表达率分别为45.9%（28/61）、62.3%（38/61）、16.4%（10/61）和60.7%（37/61）。Kaplan-Meier分析显示RAD51,RAD52,ATM和ATR是影响LMS患者OS的重要因素(P<0.05)。Cox回归分析显示RAD52、ATM和ATR是影响LMS患者OS的独立预后因子(P<0.05)。此外,ATM是LMS患者DFS的独立影响因子(P<0.05),而RAD52是PFS的独立影响因子(P<0.05)。［结论］ DNA 损伤同源重组修复相关蛋白RAD52、ATM和ATR可作为评估LMS预后的独立因子。     

乳腺化生性癌的临床病理特征及预后影响因素*

目的:分析乳腺化生性癌（metaplastic breast carcinoma,MBC ）患者的临床病理特征及其影响预后的因素。方法:收集2005年1 月至2015年1 月55例天津医科大学肿瘤医院诊治MBC 患者完整的临床病理资料。回顾性分析MBC 患者的临床病理特征、复发及生存情况。MBC 患者根据淋巴结是否转移分为淋巴结阳性组（13例）及淋巴结阴性组（39例）;根据术后是否接受化疗、放疗及内分泌治疗,将其分为化疗组（40例）和非化疗组（15例）、放疗组（12例）及非放疗组（43例）和内分泌治疗组（5 例）及非内分泌治疗组（50例）。 并且每例MBC 患者与3 例同期年龄及临床TNM 分期情况基本类似,均接受手术治疗的三阴性乳腺癌（TNBC）患者170 例匹配。结果:MBC 患者5 年无疾病生存率（disease-free survival,DFS）和总生存率（overall survival,OS）分别为45.0% 及48.2% ,显著低于TNBC 患者5 年DFS 74.7% 及OS83.5% ,且两者之间比较5 年OS和DFS 差异具有统计学意义（均P <0.001）。 肿瘤大小、淋巴结是否转移及接受化疗与否是影响患者生存预后的重要因素。化疗组5 年OS和DFS 明显高于非化疗组的OS（P = 0.008）和DFS（P = 0.033）。 淋巴结阳性组的MBC 患者接受放疗可明显提高其5 年OS（P = 0.030）。 结论:MBC 是一种侵袭性强的罕见的乳腺癌特殊类型,预后较TNBC 差,化疗使其5 年OS及DFS 获益,且以铂类为基础的化疗方案可使患者获益更大,对淋巴结阳性患者应行术后放疗。      

MDM2 gene amplification: a new independent factor of adverse prognosis in non-small cell lung cancer (NSCLC)

The prognostic impact of MDM2 amplification in non-small cell lung cancer (NSCLC) remains unknown. In this study, we investigated the occurrence of MDM2 amplification in surgically treated NSCLC patients. Molecular data were correlated with clinicopathological factors and evaluated for their prognostic value. The study group included 116 NSCLC patients who underwent pulmonary resection between 1996 and 1999. MDM2 amplification was assessed by real-time PCR using hybridization probe format on a LightCycler (Roche). The calculated ratio was a MDM2 value normalized to the amplification of the housekeeping gene phenylalaninhydroxylase (PAH). Survival curves were drawn according to the Kaplan-Meier method and compared with the use of the log-rank test. Multivariate analysis was based on Cox regression analysis. MDM2 amplification was found in 24 patients (21%). There was no relationship between MDM2 amplification and clinicopathological factors, such as sex, age and stage of disease, pT, pN, histology and tumor differentiation. Median disease-free survival (DFS) in patients with and without MDM2 amplification was 3 and 31 months, and 5-year DFS 24 and 33%, respectively (log-rank, P = 0.02). Likewise, median overall survival (OS) in patients with and without MDM2 amplification was 9 and 33 months, respectively, and 5-year OS 24 and 39%, respectively (log-rank, P = 0.01). The strong prognostic relevance of MDM2 amplification for both DFS and OS was confirmed in multivariate analysis (P < 0.01 for both comparisons). Our results suggest that MDM2 gene amplification analysis provides additional prognostic information in surgically treated NSCLC patients.     

Prognostic Outcome of Mesenchymal Transition Biomarkers in Correlation with EGFR Expression in Epithelial Ovarian Carcinoma Patients

Background: CD44 is an epithelial-mesenchymal transition (EMT) surface receptor that regulates the interactivity between the cells and the extracellular matrix, thereby promoting cell migration. The epidermal growth factor receptor (EGFR) family is a trans-membrane kinase-related protein. It regulates cell adhesion proteins, which may promote cell proliferation and invasiveness. Mesenchymal epithelial transition (MET) is another EMT receptor that stimulates cell proliferation, invasion, survival, and angiogenesis. This study aimed to evaluate the prognostic impact of CD44, EGFR expressions, and MET gene amplification in epithelial ovarian cancer (EOC). Methods: This is a retrospective cohort study, including 85 cases of EOC. CD44 and EGFR expressions were evaluated in both epithelial and stromal cells by immunohistochemistry. Tumor cells also underwent a cytogenetic analysis using fluorescent in situ hybridization (FISH) to detect MET gene amplification. Results: High CD44 expression in tumors was significantly associated with serous subtypes (P=0.001), peritoneal deposits (P=0.002), and advanced stage (P=0.002). EGFR high tumor expression demonstrated a significant association with lymph node metastasis (P=0.038) and the advanced stage of EOC (P=0.016). Increased copy number of the MET gene was significantly associated with partial therapy response (P=0.030).  CD44 and EGFR tumor high expression was associated with poor overall survival (OS). In addition, MET gene gain in tumors was associated with a shorter OS (P=0.000). Conclusion: EMT biomarkers (CD44 and MET) and EGFR expression in EOC are independent prognostic factors for OS. MET gene increase copy number was detected in cases of serous neoplasm and associated with poor survival and minimal therapy response.     

Impact of MET amplification on gastric cancer: possible roles as a novel prognostic marker and a potential therapeutic target

Identification of critical genes which play pivotal roles in controlling tumor growth and survival will establish the basis for developing therapeutic targets. With the aim of establishing personalized medicine for treatment of solid tumors, we focused on MET amplification in gastric cancer patients, given the extreme sensitivity to c-Met inhibitor in MET amplified gastric cancer cell lines. We tested MET amplification and activation of c-Met in various gastric cancer cell lines and tissue samples from 482 gastric cancer patients who underwent curative surgery. Gastric cancer cell lines with MET amplification by quantitative real-time PCR (qPCR) and FISH predicted sensitivity to PHA-665,752, a selective c-Met kinase inhibitor. Of the 472 patients who had DNA sample available for qPCR analysis, 100 patients (21.2%) had a MET copy number greater than 4.0 copies and demonstrated poorer survival following curative surgery with statistical significance (5-year OS; 50.0 vs. 59.1%; MET amplification (+) vs. MET amplification (-); P = 0.0134). These results suggest that the increased MET copy number measured by qPCR plays an important role in determining prognosis in gastric cancer patients. However, the predictive role of MET amplification for treatment response should be further explored in upcoming clinical trials.     

Prognosis of a series of 763 consecutive node-negative invasive breast cancer patients without adjuvant therapy: analysis of clinicopathological prognostic factor.

BACKGROUND AND OBJECTIVES: The objectives of this study were to confirm the favorable outcome of Japanese invasive breast cancer patients without lymph node metastasis, after treatment with surgery alone, and to evaluate clinicopathological prognostic factors in this population. METHODS: The subjects were 763 consecutive node-negative invasive breast cancer patients who underwent surgery without adjuvant therapies between 1988 and 1993 at our hospital. Disease-free survival (DFS) and overall survival (OS) rates were analyzed by clinicopathological factors. RESULTS: The median age of the patients at surgery was 52 years and the median follow-up period of patients was 74 months. At 5 years, the respective DFS and OS rates of all patients were 90.8% and 93.9%. Patients with a pathological tumor size of invasive component of more than 2 cm (319 patients) had a significantly lower DFS than those with tumors measuring 2 cm or less (361 patients) (P = 0.045). Patients with positive hormone receptor status (280 patients) (estrogen and/or progesterone receptor positive) tended to have a better OS than those negative for both hormone receptors (92 patients) (P = 0.078). Meanwhile, patients with tumors of histological grade 3 (328 patients) had a much poorer prognosis than those with tumors of histological grade 1 or 2 (413 patients) (P = 0.008 for OS and P = 0.042 for DFS). The respective 5-year DFS and OS rates of patients with histological grade 3 tumors larger than 2 cm in pathological tumor size of invasive component (195 patients) were 85.5% and 87.6%, indicating that these node-negative patients form a high risk group. CONCLUSIONS: Japanese invasive breast cancer patients without lymph node metastasis tended to show a survival advantage compared with their Caucasian counterparts. Histological grade was the most useful prognostic factor in this population.     

Prognostic significance of cyclooxygenase‐2 in cervical cancer: A meta‐analysis

Published data on the prognostic value of cyclooxygenase‐2 (COX‐2) overexpression in cervical cancer are conflicting and heterogeneous. We performed a meta‐analysis to more precisely estimate its prognostic significance. The pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the effects. Twenty‐three studies with 1,477 cervical cancer patients were selected to evaluate the association between COX‐2 and overall survival (OS), disease‐free survival (DFS), response to chemoradiation (RC) and clinicopathological parameters. High COX‐2 expression predicted poor OS (HR: 2.53, 95% CI: 1.54–4.18), DFS (HR: 2.41, 95% CI: 1.58–3.69) and RC (OR: 3.03, 95% CI: 1.97–4.64). Subgroup analyses showed that COX‐2 overexpression was related significantly with poor OS in patients treated by chemoradiation or surgery, and in patients with squamous cell carcinoma, respectively. Besides, COX‐2 overexpression was related significantly with poor DFS in chemoradiation subgroup. Furthermore, COX‐2 overexpression was associated with poor RC in patients who received “FP” regimen or “P” regimen. Additionally, there were significant associations between COX‐2 expression and all clinicopathological parameters except tumor grade. The pooled ORs (95% CI) were as follows: 1.49 (1.09–2.04) for age, 1.77 (1.22–2.56) for lymph node metastasis, 1.04 (0.74–1.47) for tumor grade, 1.71 (1.12–2.64) for tumor size, 2.38 (1.28–4.45) for FIGO stage, 3.96 (2.32–6.77) for histological type, 2.45(1.10–5.42) for parametrical involvement. This meta‐analysis indicated that COX‐2 overexpression might be an unfavorable prognostic and a chemoradiation resistance predictive factor for cervical cancer; it could potentially help to stratify patients further in clinical treatment.     

HER-2/neu gene amplification by fluorescence in situ hybridization allows risk-group assessment in node-negative breast cancer

In a collective of 112 node-negative breast cancer patients, we compared the prognostic impact of HER-2/neu gene amplification (AMP) determined by fluorescence in situ hybridization (FISH) and HER-2/neu protein overexpression (EXP) measured by immunohistochemistry (IHC) with traditional prognostic factors (tumor size, grade, steroid hormone receptor status, menopausal status) and tumor invasion markers uPA (urokinase-type plasminogen activator) and its inhibitor PAI-1 determined by enzyme immunoassay (ELISA). Median follow-up in patients still alive at time of analysis was 7 years. Automated FISH and IHC were performed on parallel-cut formalin-fixed paraffin-embedded tissue sections. HER-2/neu AMP was detected by FISH in 31% and HER-2/neu EXP was measured by IHC in 41% of the cases. In 13% of the tumors, both AMP and EXP were found. FISH and IHC results were concordant in 56% of all analyzed cases. In univariate analysis, HER-2/neu AMP significantly predicted both disease-free (DFS) and overall survival (OS). HER-2/neu EXP was significant for OS, only. In multivariate analysis of all analyzed prognostic factors, HER-2/neu AMP was the only independent predictive factor for both DFS and OS. CART analysis revealed that HER-2/neu AMP together with the combination uPA/PAI-1 allowed optimal risk-group assessment after a 7-year median follow-up: patients with low levels of both uPA and PAI-1 and no HER-2/neu AMP had a significantly lower relapse rate (4.6%) than the remaining patients (32%). In conclusion, HER-2/neu gene AMP determined by FISH allowed a more accurate risk-group assessment than HER-2/neu protein EXP measured by IHC. Combining the HER-2/neu gene status measured by FISH with levels of tumor invasion markers uPA and PAI-1 improves clinically relevant risk-group assessment. In addition to its prognostic strength, the significant impact of HER-2/neu AMP on OS may reflect its ability to predict resistance to systemic therapy.     

178例三阴性乳腺癌的临床病理特征及生存分析

 目的
探讨三阴性乳腺癌(TNBC)患者的临床病理特点、生存情况和预后影响因素。方法收集雌激素受体(ER)、孕激素受体
(PR)和人表皮生长因子受体2(HER2)均阴性的178例乳腺癌患者的临床病理资料,观察其长期生存状况。分析其临床
特点及影响预后的因素。结果有乳腺癌家族史的患者4例。主要病理类型为浸润性导管癌(155/178,87.1%）。组织
学分级多为Ⅲ级(53.1%）。中位肿瘤最大径2.8 cm(0.2～12 cm）,T1、T2期患者160例占89.9%。108例(61.7%）
患者无淋巴结转移。分期为Ⅰ、Ⅱ、Ⅲ期的患者分别有60例(33.7％)、81例(45.5％)、31例(17.4％)。58例(48.3
％)患者p53阳性。中位随访时间74月(10～156月）,5年
无病生存(DFS)和总生存(OS)率分别是76.9%和86.1%。单因素分析显示T分期、临床分期及淋巴结转移对DFS和OS
均有显著影响。多因素分析显示,淋巴结转移是DFS及OS的独立影响因素。而术后分期是OS的影响因素。共有41例
患者出现复发转移及第二原发肿瘤,常见转移部位依次为骨转移、局部复发或同侧锁骨上淋巴结转移、肺或胸膜转
移、肝转移及脑转移。结论 本组TNBC肿瘤直径较小,组织学分级低分化比例较高(53.1%）。复发转移以骨转移、
局部复发及肺转移为主。淋巴结转移及术后分期是总生存的独立危险因素。     

Prognostic value of MET protein overexpression and gene amplification in locoregionally advanced nasopharyngeal carcinoma

This study assessed the incidence and prognostic value of MET protein overexpression and gene amplification in locoregionally advanced nasopharyngeal carcinoma (NPC). Specimens from 376 consecutive patients with locoregionally advanced NPC were subjected to immunohistochemistry to analyze MET protein expression and fluorescence in situ hybridization to assess MET amplification status. In total, 139/376 (37.0%) patients had MET protein overexpression; of whom, 7/139 (5.0%) had MET amplification. MET overexpression was significantly associated with locoregional failure (P = 0.009), distant metastasis (P = 0.006) and death (P < 0.001); MET amplification was significantly associated with death (P = 0.021). A positive correlation was observed between MET copy number status and MET protein expression (r = 0.629, P < 0.001). Multivariate analysis demonstrated MET overexpression was an independent prognostic factor for overall survival (OS; HR, 1.99; 95% CI, 1.38–2.87; P < 0.001) and disease-free survival (DFS; HR, 1.85; 95% CI, 1.33–2.57; P < 0.001), and MET amplification was independently associated with poorer OS (HR, 4.24; 95% CI, 1.78-10.08; P < 0.001) and DFS (HR, 5.44; 95% CI, 2.44-12.09; P < 0.001). In conclusion, MET protein overexpression and gene amplification are independent prognostic factors for OS and DFS in locoregionally advanced nasopharyngeal carcinoma, and may provide therapeutic biomarkers to identify patients in whom MET inhibitors may be beneficial.     

炎症反应标志物和营养状况对食管胃结合部腺癌患者术后预后的评估价值

目的:明确基于系统性炎症评分和营养状况对食管胃结合部腺癌（adenocarcinoma of esophagogastric junction,AEG）患者术后预后的影响。方法:回顾性收集2010年03月至2019年03月我院451例AEG手术患者的临床资料,以及炎症-营养标志物（NLR、LMR、AGR、ALI、mGPS和PNI）。根据受试者工作特征（ROC）曲线获取截断值并分组,NLR、LMR、AGR、ALI和 PNI的截断值分别为3.76、3.01、1.30、27.55、42.68;COX模型分析患者预后的影响因素;采用Kaplan-Meier方法绘制生存曲线,Log-Rank检验比较组间生存差异。结果:患者无疾病生存期（DFS）与肿瘤分化程度、肿瘤大小、脉管癌栓、T分期、N分期、pTNM分期、血红蛋白、NLR、PNI、LMR、ALI相关（P＜0.05）,总生存期（OS）与肿瘤分化程度、肿瘤大小、脉管癌栓、T分期、N分期、pTNM分期、NLR、AGR、PNI、LMR、ALI相关（P＜0.05）。在多因素分析中,脉管癌栓、pTNM分期、ALI是DFS的独立影响因素,而LMR、PNI、pTNM分期则是OS的独立影响因素。Kaplan-Meier生存曲线显示,PNI<42.68, LMR<3.01及ALI<27.55患者的DFS和OS均更短（P＜0.05）。结论:炎症反应和营养状况与术后AEG患者临床病理因素及预后相关,ALI是AEG患者无疾病生存期的独立影响因素;PNI及LMR是AEG患者总生存期的独立影响因素。