放疗延迟对乳腺癌不同分子亚型患者预后的影响

目的 探讨放疗延迟对乳腺癌不同分子亚型患者预后的影响。方法 收集2007年1月—2012年12月在我院行乳腺癌根治术患者341例,其中Luminal A型149例(对照组83例,放疗延迟组66例),Luminal B型105例(对照组63例,放疗延迟组42例),HER2+型43例(对照组28例,放疗延迟组15例),三阴型患者44例(对照组27例,放疗延迟组17例)分析放疗延迟组与对照组预后是否存在差异。结果 Luminal A型、Luminal B型、HER2+型、三阴性型在对照组和放疗延迟组的局部复发率分别为(4.8% vs. 9.1%,P=0.301),(4.7% vs. 19.0%,P=0.019),(7.1% vs. 33.3%,P=0.027),(11.1% vs. 35.3%,P=0.053);远处转移率分别为(9.6% vs. 10.6%,P=0.845),(11.1% vs. 14.2%.P=0.234),(32.1% vs. 40.0%,P=0.937),(37.0% vs. 41.2%,P=0.784);无瘤生存率分别为(85.5% vs. 80.3%,P=0.395),(84.1% vs. 66.7%,P=0.037),(60.7% vs. 33.3%,P=0.087),(55.5% vs. 23.5%,P=0.037);总生存率分别为(94.0% vs. 90.9%,P=0.539),(84.1% vs. 80.9%,P=0.672),(67.9% vs. 60.0%,P=0.606),(59.2% vs. 41.2%,P=0.242)。Cox回归分析结果显示肿瘤大小(HR=3.156,P=0.043)、淋巴结转移(HR=1.074,P=0.001)、TNM(HR=8.591,P=0.009)和分子亚型(HR=2.092,P＜0.001)为乳腺癌患者预后的独立影响因素。结论 Luminal B型及HER2+型患者的局部复发率均因放疗延迟而明显增高,Luminal B型及三阴型的无瘤生存率因放疗延迟而明显降低。肿瘤大小、淋巴结转移、TNM分期和分子亚型是影响患者总生存期的独立危险因素。     

Copine-8在胃癌组织中的表达与临床病理特征及预后的相关性

目的 探讨Copine-8(CPNE8)在胃癌组织中的表达与患者临床病理特征及预后的相关性。方法 收集2011年3月—2014年3月于仙桃职业学院附属医院行胃癌根治术并经过病理证实的胃癌组织标本144例,采用免疫组织化学分析CPNE8在胃癌及其配对的癌旁组织中的表达情况,并分析其与胃癌临床病理参数及预后的关系。结果 免疫组织化学结果表明,CPNE8阳性表达率在胃癌组织中较癌旁组织中明显升高(63.9% vs. 26.4%,χ²=36.450,P＜0.001);CPNE8的表达与胃癌患者的TNM分期及有无淋巴结转移密切相关(χ²=5.993,P=0.014;χ²=6.703,P=0.009)。Kaplan-Meier生存分析发现,CPNE8高表达患者总生存时间(OS)和无病生存时间(DFS)均明显短于CPNE8低表达患者(χ²=23.130,P＜0.001;χ²=21.570,P＜0.001)。TNM分期(HR=1.297,95% CI:1.018~1.652,P=0.036)、淋巴结转移(HR=1.340,95% CI:1.027~1.749,P=0.031)和CPNE8蛋白表达(HR=1.531,95% CI:1.208~1.940,P＜0.001)是影响胃癌患者OS的独立危险因素;TNM分期(HR=1.280,95% CI:1.028~1.593,P=0.027)和CPNE8蛋白表达(HR=6.010,95% CI:1.355~26.661,P=0.018)是影响胃癌患者DFS的独立危险因素。结论 CPNE8在胃癌组织中显著表达上调,并与患者恶性病理特征密切相关,CPNE8可成为胃癌患者预后评估的标志物之一。     

外周血中CEA和CA19-9的表达水平在进展期胃癌中的预后价值

目的 探讨外周血中CEA和CA19-9的表达水平在进展期胃癌中的预后价值及进展期胃癌患者预后的影响因素。方法 选取2010年1月—2010年12月于哈尔滨医科大学附属肿瘤医院胃肠外科行R0根治术的进展期胃癌患者255例,根据CEA和CA19-9的表达水平分为A组(CEA＜2.19ng/mL且CA19-9＜10.78U/mL)、B组(CEA≥2.19ng/mL或CA19-9≥10.78U/mL)和C组(CEA≥2.19ng/mL且CA19-9≥10.78U/mL),比较三组进展期胃癌患者的临床病理资料和生存情况,并分析进展期胃癌患者预后的影响因素。结果 三组进展期胃癌患者间临床N分期、临床TNM分期和病理TNM分期的差异均具有统计学意义(P＜0.05),三组进展期胃癌患者术后中位生存时间差异无统计学意义(P＞0.05);术后1年、3年、5年生存率差异无统计学意义(P＞0.05),但A组1年、3年、5年生存率高于B组和C组。影响胃癌预后的因素包括肿瘤分化程度、病理T分期、病理TNM分期、清扫淋巴结总数、清扫淋巴结阳性数、淋巴结转移情况。结论 CEA和CA19-9联合检测对进展期胃癌患者评估预后有一定的参考价值。     

术后辅助化疗后复发转移与初次诊断的IV期NSCLC一线化疗疗效分析

目的 既往行根治性手术治疗的非小细胞肺癌(NSCLC)患者,即使进行了系统的术后辅助化疗,仍有很多不可避免的复发,甚至远处转移。同时,很多患者在初治时即为Ⅳ期。本文旨在探讨术后辅助化疗后远处转移的NSCLC患者一线化疗(First-line chemotherapy at recurrence post-adjuvant chemotherapy,FCRPC)与初治Ⅳ期NSCLC患者一线化疗(Initial first-line chemotherapy,IFC)的疗效对比。方法 研究对象为603例远处转移非小细胞肺癌患者,其中73例为FCRPC组,530例为IFC组。采用倾向性评分匹配的统计学方法平衡两组间的临床特征,卡方检验进行两组间近期疗效对比。并采用Cox回归分析法和Kaplan-Meier分析法进行生存分析。结果 在远处转移NSCLC患者中,FCRPC组的客观有效率(ORR)及疾病控制率(DCR)与IFC组无统计学差异(ORR率:FCRPC组27.4% vs. IFC组24.7%,P=0.851;DCR率:FCRPC组78.1% vs. IFC组65.6%,P=0.140)。FCRPC组与IFC组的中位无进展生存期(中位PFS:9.8个月 vs. 8.5个月,P=0.337)与中位总生存期(中位OS:20.0个月 vs. 14.4个月,P=0.087)均无统计学差异。结论 术后辅助化疗后远处转移NSCLC与初治Ⅳ期NSCLC患者一线化疗的预后无统计学差异。     

外周血STAT1,STAT3基因启动子CpG岛甲基化状态与大肠癌预后关系的研究

目的 探讨大肠癌(CRC)患者外周血STAT1,STAT3基因启动子CpG岛甲基化状态与大肠癌预后的关系以及影响大肠癌患者预后生存的因素。方法 采用队列研究的方法,对哈尔滨医科大学附属肿瘤医院病理确诊的原发性大肠癌住院患者239例进行生物学采样并随访,通过甲基化特异性高分辨率熔解曲线(MS-HRM)分析STAT1,STAT3基因启动子CpG岛甲基化状态。结果 239例大肠癌患者术后1年、3年和5年的生存率分别为为94.90%、86.00%和67.20%。STAT1,STAT3基因甲基化状态与大肠癌患者术后生存期无关(STAT1:HR=0.85,95% CI:0.55~1.30,P=0.44;STAT3:HR=0.75,95% CI:0.36~1.58,P=0.45),Dukes分期(HR=1.31,95% CI:1.14~1.51,P＜0.01)和术中肠吻合器的使用(HR=1.98,95% CI:1.25~3.14,P＜0.01)是影响大肠癌患者预后的重要因素,Dukes分期为C、D期的患者死亡风险显著高于A、B期(HR=1.31,95% CI:1.14~1.51,P＜0.01),术中使用肠吻合器的患者预后优于没有使用肠吻合器的患者。而性别、年龄、肿瘤位置、肿瘤大体分型、组织学分型、术后化疗与大肠癌的预后无关。结论 Dukes分期是影响大肠癌预后生存的独立因素,术中使用肠吻合器患者预后优于未使用者,外周血STAT1,STAT3基因甲基化状态尚不能作为影响大肠癌患者预后的生物标志物。     

SRC1在胃癌中的表达及其与预后的关系

目的 探讨类固醇受体辅助活化因子-1(Steroid receptor coactivator 1,SRC1)蛋白在胃癌组织中的表达及其与患者临床病理参数和预后的相关性。方法 收集36例胃癌组织及其配对的癌旁组织,qRT-PCR法及Western blot法检测SRC1mRNA和蛋白的表达水平。应用免疫组化方法检测286例胃癌组织中SRC1蛋白的表达情况,分析SRC1蛋白表达与胃癌临床病理参数的关系及其对患者预后的影响。结果 与癌旁组织相比,胃癌组织中SRC1mRNA表达水平明显降低(P=0.004),SRC1蛋白表达水平也明显降低。SRC1蛋白的表达强度与胃癌患者临床病理参数无显著关系。Kaplan-Meier生存曲线分析发现高表达SRC1组5年生存率显著高于低表达组(P=0.009)。Cox回归分析结果显示低表达SRC1(P=0.002)、肿瘤侵袭T_4a~T_4b(P=0.004)、淋巴结转移N(P=0.038)、远处转移M1(P＜0.001)是独立影响总生存时间的预后不良因素。SRC1低表达较高表达患者预后差。结论 胃癌中SRC1的表达明显降低,胃癌组织中的SRC1表达水平可作为独立的胃癌预后不良因素,其过低表达与胃癌的发展密切相关,可能作为一个抑癌基因及判断胃癌患者预后的标志物。     

中性粒细胞和血小板与淋巴细胞比值对食管鳞癌临床病理特征及预后的意义

目的：探讨中性粒细胞/淋巴细胞比值（NLR）、血小板/淋巴细胞比值（PLR）与食管鳞癌临床病理特征及手术预后的关系,为食管鳞癌的临床治疗提供参考。方法：回顾性分析河北医科大学第四医院2010年1月1日—2013年12月31日收治的食管鳞癌手术患者,共134例。分析NLR、PLR与食管鳞癌临床病理特征及手术预后的关系。结果：低NLR （< 2.34）组患者T分期早于高NLR （≥2.34）组患者（P=0.001）;低PLR （< 152.76）组患者T分期早于高PLR （≥152.76）组患者（P < 0.01）。低NLR （< 2.12）组患者病变长度小于高NLR （≥2.12）组患者（P < 0.01）;低PLR （< 103.91）组患者病变长度小于高PLR （≥103.91）组患者（P < 0.01）。全组患者1、3、5年生存率分别为88.1%、45.8%、33.9%,局部控制率分别为88.0%,69.0%,67.4%,1、3、5年远处转移率分别为27.6%、54.9%、55.9%;其中高NLR组患者1、3、5年远处转移率显著高于低NLR组（P=0.012）,高PLR组患者1、3、5年远处转移率显著高于低PLR组（P=0.014）。多因素分析显示仅N分期是患者生存的独立影响因素（P=0.014）。结论：NLR、PLR与食管癌患者的临床病理特征和预后密切相关,高NLR和高PLR的患者T分期较晚,病变长度较长,且更易出现远处转移。     

外周血USP1基因甲基化与大肠癌预后风险的关系

目的 探讨外周血中去泛素化酶USP1甲基化及临床特征与大肠癌预后风险的关系。方法 采用队列研究,共纳入286例大肠癌患者。使用高分辨率熔解曲线分析法(HRM)检测基因甲基化水平。应用Cox回归模型评估基因甲基化及临床特征与大肠癌预后风险之间的关联。结果 在男性大肠癌病例中,USP1甲基化增加预后不良风险(HR=2.091,95% CI:1.195~3.661,P=0.010)。临床病理特征中,UICC肿瘤分期4期(HR=2.464,95% CI:1.205~5.039,P=0.014)、肿瘤大小超过50mm(HR=1.610,95% CI:1.016~2.550,P=0.043)和组织学非腺型(HR=5.117,95% CI:1.142~22.930,P=0.033)是大肠癌不良预后风险增加的影响因素。结论 UICC肿瘤分期4期、肿瘤大小超过50mm和组织学分型为非腺型会增加大肠癌不良预后风险。外周血USP1基因启动子区甲基化与男性大肠癌预后不良风险增加有关。     

术前炎症相关指标与可切除胃癌患者预后的相关性

目的 探讨术前外周血系统性免疫炎症指数(Systemic immune-inflammation index,SII)、中性粒细胞与淋巴细胞比值(Neutrophil to lymphocyte ratio,NLR)、血小板与淋巴细胞比值(Platelet to lymphocyte radio,PLR)与可切除胃癌患者预后的相关性及其临床意义。方法 回顾性分析2013年10月—2015年2月哈尔滨医科大学附属肿瘤医院收治的226例经手术治疗胃癌患者的临床病理资料。评估并比较SII、NLR、PLR在可切除胃癌患者中的预后价值。结果 胃癌组SII、NLR、PLR显著高于健康对照组,差异均有统计学意义(P＜0.05)。多因素Cox回归分析结果显示SII高(HR=2.947,95% CI:1.345~6.454,P=0.007)、NLR高(HR=2.876,95% CI:1.445~5.724,P=0.003)、T分期越高(HR=5.885,95% CI:1.641~21.099,P=0.007)、有远处转移(HR=3.010,95% CI:1.472~6.154,P=0.003)是影响可切除胃癌患者预后的独立危险因素。SII预测可切除胃癌患者结局的ROC曲线下面积为0.840,灵敏度为86.6%,特异度为68.0%,高于NLR、PLR及CA199,且差异有统计学意义(P＜0.05)。结论 SII对可切除胃癌患者生存结局的评估价值优于NLR和PLR。     

血清中microRNA-127对鼻咽癌患者化疗抗性的预测价值

目的 探讨血清微小RNA(micro RNA)在预测鼻咽癌患者化疗有效性方面的临床价值。方法 纳入2010年1月—2016年12月我院收治的187例接受顺铂联合化疗的鼻咽癌患者,其中化疗敏感患者123例,化疗抵抗患者64例。检测所有初次化疗前血清中miRNA的表达水平,并以健康体检人群为对照,评估血清miRNA与鼻咽癌患者化疗有效性的关系及其预测价值。结果 鼻咽癌患者血清miR-127水平显著高于健康对照组(4.3±1.6 vs. 1.4±0.5)(P＜0.001),化疗抵抗患者的血清miR-127水平显著高于化疗敏感患者(4.5±1.3 vs. 3.8±1.7)(P＜0.001)。ROC曲线显示血清miR-127对鼻咽癌患者化疗抵抗的预测价值较好(AUC=0.702,P＜0.001),最佳阈值为4.2,灵敏度82.3%,特异度76.3%。与化疗敏感组相比,化疗抵抗组患者的T_3-4期、N₃期和TNM Ⅲ~Ⅳ期患者比例均明显升高(P＜0.01),且miR-127≥4.2的比例也升高(P＜0.001)。多因素Logistics回归分析显示TNM分期(OR=1.655,95% CI:1.142~2.584,P=0.016)和血清miR-127≥4.2(OR=2.231,95% CI:1.762~4.503,P=0.001)是影响鼻咽癌患者化疗抵抗的独立危险因素。结论 血清miR-127水平的升高可能是预测鼻咽癌患者化疗抵抗的重要危险因素。     

Prognostic significance of p53, nm23, PCNA and c-erbB-2 in gastric cancer

BACKGROUND: Although the TNM stage is the most important prognostic factor for gastric cancer, there is a need for new prognostic and predictive factors, because the prognosis varies among patients of the same stage. The purpose of this study was to clarify the relationship of p53, nm23, proliferating cell nuclear antigen (PCNA) and c-erbB-2 with the clinicopathological parameters and the survival results. METHODS: For 841 patients who had undergone gastrectomy for gastric cancer at Seoul National University Hospital from July 1996 to December 1997, the expression levels of p53, nm23, PCNA and c-erbB-2 in gastric cancer tissues were examined immunohistochemically. Also, the clinicopathological parameters such as gender, age, operation type, TNM stage and size of the tumor, histology and Lauren classification were analyzed retrospectively. RESULTS: There were 568 males and 273 females (2.07:1) with a mean age of 56 years (range:25-82 years). The percentages of positive expression of p53, nm23 and c-erbB-2 were 43, 74 and 17%, respectively; 59% of tumors expressed PCNA index > or =50. p53 expression was associated with age, gender, tumor size, histology, Lauren classification, stage, nm23 expression, PCNA index >or =50 and c-erbB-2 expression. nm23 expression was associated with age, tumor size, Borrmann type, histology, Lauren classification and stage. PCNA index > or =50 was associated with age, gender, tumor size, Borrmann type, histology, Lauren classification and c-erbB-2 expression. c-erbB-2 expression was associated with gender, Borrmann type, histology and Lauren classification. p53 and nm23 were related with poor prognosis in univariate analysis. nm23 was related with poor prognosis of stage III and diffuse-type gastric cancer in univariate subgroup analysis. However, in a multivariate study, these prognostic impacts were not maintained. CONCLUSION: The expression of p53 and nm23 seems to be related with poor prognosis of gastric cancer patients who have undergone gastrectomy. However, the prognostic significance was not revealed by a multivariate analysis.     

p53在弥漫型胃癌中的表达研究

[目的]研究 p53蛋白表达在胃癌预后中的意义。[方法]采用免疫组织化学LSAB法 ,对152例胃癌组织中 p53蛋白表达进行检测 ,分析 p53表达与临床病理因素及预后之间的关系。[结果]p53蛋白表达阳性率为24 3%(37/152) ,其表达与胃癌各临床病理因素之间无明显相关性。p53表达在肠型胃癌与弥漫型胃癌之间不同 ,生存率分析显示 ,p53表达的不良预后者仅见于弥漫型胃癌而非肠型胃癌。[结论]p53蛋白表达可用于识别弥漫型胃癌中具侵袭性并伴不良预后的亚组胃癌病例     

Vascular endothelial growth factor receptor-3 is a favorable prognostic factor in advanced gastric carcinoma

Vascular endothelial growth factor receptor (VEGFR)-3 is a receptor for VEGF-C and D and is implicated in the development of lymphatic vessels and metastasis. The purpose of this study was to investigate the expression of VEGFR-3 and its clinicopathological significance in primary gastric carcinoma (GC). Pathological and clinical findings from 109 GC cases were reviewed and VEGFR-3 expression was examined using immunohistochemistry. The clinicopathological implications of VEGFR-3 expression were analyzed statistically. VEGFR-3 expression was evaluated for intensity (0-3) and proportion (0-100%). A total score was obtained by multiplying the intensity by the proportion (0-300). A total score of 82 or more was considered positive for VEGFR-3. Of the 109 patients with GC, 19 (17.4%) were positive for VEGFR-3. VEGFR-3 expression was associated with Lauren classification (68.4% for intestinal type, 31.6% for diffuse type, p=0.058). It was more frequent in early gastric cancer (EGC), 28.0% in EGC, 16.2% in advanced gastric carcinoma (AGC), though this difference was not statistically significant. In 78 patients with AGC, VEGFR-3 expression was associated with good overall survival (p=0.052). In a multivariate analysis, the pTNM stage and VEGFR-3 were independent prognostic factors (OR=3.35, p=0.002 for pTNM stage; OR=0.23, p=0.044 for VEGFR-3). However, the expression of VEGFR-3 in EGC was not correlated with overall survival. In conclusion, the expression of VEGFR-3 was associated with the intestinal type (based on Lauren classification) and may be a favorable prognostic factor in AGC.     

胃癌根治术后切缘阳性患者的临床病理特征和预后分析

  目的  探讨胃癌根治术后切缘阳性患者的临床病理特征及其对预后影响。  方法  回顾性分析河北医科大学第四医院2011年1月至2016年1月收治的胃癌根治术后切缘阳性患者的临床病理资料。按1∶2随机数法选取同期收治的切缘阴性患者,比较阳性和阴性切缘患者的一般临床病理学特征及预后情况。  结果  共纳入73例切缘阳性患者,与同期纳入的146例切缘阴性病例比较,阳性组的肿瘤直径更大、更多位于贲门或全胃,组织学类型更差、Lauren分型趋于弥漫型、Borrmann分型多为Ⅲ～Ⅳ型、肿瘤浸润深度以T4a～4b为主、pTNM分期更晚,脉管浸润率及淋巴结转移率也更高,同时术者经验、手术方式的差异也与阳性切缘发生有关（均P<0.05）。全组共有205例患者获得完整随访,两组患者5年总生存（overall survival,OS）率及无进展生存（progression-free survival,PFS）率均有显著性差异（23.19% vs. 58.82%,15.94% vs. 47.06%,均P<0.001）。Cox多因素分析显示,切缘状态（P=0.012）、pTNM分期（P=0.023）及术后综合治疗（化疗/化疗联合放疗）（P<0.001）是影响胃癌预后的独立因素。  结论  胃癌根治术后切缘状态与多种临床病理特征相关,切缘阳性患者预后较差。      

Prognostic Value of Caveolin-1 Expression in Gastric Cancer: a Meta-analysis

The relationship between caveolin-1 (Cav-1) and clinicopathological characteristics of gastric cancer iscontroversial, although Cav-1 plays an important role in tumor metastasis. To evaluate the clinicopathologicaland prognostic value of expression in patients with gastric cancer, a meta-analysis was performed to investigatethe impact on clinicopathological parameters and prognosis in gastric cancer cases. Studies assessing theseparameters for Cav-1 in gastric cancer were identified up to June 2014. Finally, a total of six studies met theinclusion criteria. Our combined results showed that Cav-1 expression was significantly associated with theLauren classification (pooled OR=0.603, 95% CI: 0.381-0.953, P=0.030). Furthermore, we found that Cav-1expression predicted a better overall survival in gastric cancer patients (pooled OR=0.590, 95% CI: 0.360-0.970,P=0.038, fixed-effect). In conclusion, the overall data of the present meta analysis showed that Cav-1 expressionwas not correlated with clinicopathological features except for the Lauren classification. Simultaneously, Cav-1overexpression predicted a better overall survival in gastric cancer. Cav-1 expression in tumors is a candidatepositive prognostic biomarker for gastric cancer patients.     

Expression of sialyl-Tn in gastric cancer: correlation with known prognostic factors.

Sialyl-Tn (STn) is a core region carcinoma-associated carbohydrate determinant expressed on cancer-associated mucins. Expression of STn has been associated with poor prognosis in colon and ovarian cancer, independent of other prognostic factors such as tumour grade, stage or histological type. Recent studies have suggested that STn expression may be an independent prognostic variable in gastric cancer. We have examined 158 patients with gastric cancer using the antibody B72.3 (Biomira, Edmonton, Alberta, Canada). Of these, 110 patients (70%) expressed STn. Expression of STn did not correlate with tumour differentiation or the Ming classification, but expression was noted more frequently in the relatively good prognosis intestinal type of tumours (chi 2 = 6.9, P = 0.03). Conversely, early-stage cancers showed a significantly lower frequency of expression than more advanced cases (chi 2 = 13.75, P = 0.003). In this patient group, STn expression did not influence survival, and in multivariate regression analysis only tumour stage and Lauren classification were found to be independent prognostic variables.     

胃癌HER-2表达和Lauren分型的相关性研究进展

HER-2的过表达与胃癌的发生、浸润、种植与转移过程相关。一直以来关于胃癌的临床分期和病理诊断标准有很多且争论较多,Lauren分型是临床中简便且有效的胃癌分类方法之一,根据胃癌的组织形态和细胞特点分为弥漫型、肠型和混合型。一些研究表明,肠型胃癌预后好于弥漫型胃癌,且肠型胃癌中HER-2阳性率较高,这些可能都会影响HER-2预测胃癌预后的因素。胃癌HER-2过表达和Lauren分型的关系如何,两者影响患者生存期的因素有哪些,两者结合能否成为胃癌最好的预测因子等尚待研究。本文就胃癌HER-2表达和Lauren分型的相关性研究进展进行综述。     

Minichromosome maintenance 2 (MCM2) immunoreactivity in stage III human gastric carcinoma: clinicopathological significance

Background The origin licensing factor minichromosome maintenance 2 (MCM2) has recently been identified as a critical regulator of proliferation in both normal and neoplastic cells. This study examined whether MCM2 expression was of prognostic relevance in patients with stage III gastric carcinoma and whether the expression of this marker showed any correlation with clinicopathological characteristics. In addition, we evaluated whether the expression of this proliferation marker was correlated with that of another marker, Ki-67, in gastric carcinoma. Methods We examined the immunohistochemical expression of MCM2, Ki-67, and p53 in 103 surgically removed stage III gastric carcinomas, which consisted of 60 intestinal-type and 43 diffuse-type carcinomas. The labeling indices (LIs) of MCM2 and Ki-67 in cancer cells were compared with clinicopathological characteristics, p53 expression, and overall survival rates. Results The mean MCM2 and Ki-67 LIs were 69.1 ± 11.8% and 48.2 ± 14.5%, respectively, in the intestinal carcinomas, and 43.7 ± 9.9% and 24.9 ± 11.0%, respectively, in the diffuse carcinomas. The LIs of these proteins revealed no significant association with clinicopathological characteristics or with p53 expression in the carcinomas. Kaplan-Meier survival curves showed that, in the patients with diffuse carcinoma, those with higher MCM2 LIs had a poorer prognosis (P < 0.05), but the MCM2 LI was not correlated with prognosis for those with intestinal carcinoma (P = 0.25). Ki-67 expression had no significant correlation with prognosis in either intestinal-type or diffuse-type carcinomas. Multivariate Cox regression analysis confirmed that MCM2 was an independent prognostic factor in patients with diffuse carcinoma. Conclusion Our data suggest that MCM2 is a useful prognostic marker in patients stage III diffuse-type gastric carcinoma.     

Subtraction of Epstein–Barr virus and microsatellite instability genotypes from the Lauren histotypes: Combined molecular and histologic subtyping with clinicopathological and prognostic significance validated in a cohort of 1,248 cases

Limited studies investigated clinicopathological and prognostic significance of histologic and molecular subgroups of gastric cancer concurrently. We retrospectively enrolled 1,248 patients with gastric cancer who received radical gastrectomy with lymphadenectomy and classified these cases into the Epstein–Barr virus (EBV)-associated and microsatellite instability (MSI)-associated subtypes by EBV-encoded small RNA in situ hybridization and immunohistochemical stains for DNA mismatch repair proteins, respectively. The remaining cases were categorized as the Lauren intestinal and diffuse/mixed subtypes. The clinicopathological and prognostic significance of the subtypes was examined by statistical analysis. In total, 65 (5.2%), 116 (9.3%), 496 (39.7%), 431 (34.5%) and 140 (11.2%) cases were identified as EBV-associated, MSI-associated, intestinal, diffuse and mixed subtypes, respectively. The EBV-associated, MSI-associated, intestinal and diffuse/mixed subtypes exhibited distinctive clinicopathological characteristics, including differences in age, gender, stump cancer, gastric location, tumor size, TNM stage, margin involvement, lymphatic/perineural invasion, HER2 status and recurrence pattern. The log-rank test showed survival discrimination (p < 0.001), and the multivariate analysis identified EBV-associated and MSI-associated cases demonstrated better outcomes than the diffuse/mixed subtype (EBV, HR 0.464, 95% CI 0.296–0.727, p = 0.001; MSI, HR 0.590, 95% CI 0.407–0.856, p = 0.005). EBV-associated lymphoepithelioma-like carcinoma cases had the most favorable outcome (HR 0.138, 95% CI 0.033–0.565, p = 0.006). In different clinical groups, the subtypes exhibited survival discrepancies. The EBV-associated and diffuse/mixed cases exhibited more favorable response to chemotherapy. In conclusion, this combined classification, in parallel with the molecular subtypes specified in the Cancer Genome Atlas study, has implications for the clinical management of gastric cancer.     

Clinicopathological significance of cathepsin D expression in gastric adenocarcinoma

OBJECTIVE: An estrogen-regulated lysosomal protease, cathepsin D, has been detected in a variety of tissues. This proteinase has been described as closely associated with tumor progression and metastasis in malignant tumors. The purpose of this study was to determine the clinicopathological and prognostic significance of cathepsin D expression in gastric adenocarcinoma. METHODS: In a consecutive series of 478 patients with gastric carcinoma (median follow-up period: 93 months, range: 1-285 months), cathepsin D expression in tumors was quantitatively analyzed with immunohistochemistry using a monoclonal antibody against cathepsin D (clone: 1C11). The percentage of cathepsin-D-positive cancer cells (the CD index) was calculated. In addition, the amount of cathepsin-D-positive stromal cells was evaluated; three grades (high, intermediate, and low) were used for the classification. RESULTS: The mean CD index of 478 tumors was 12.8% (range: 0-100%, median: 8%). The mean CD index of diffuse-type gastric carcinomas (14.9%) was significantly higher than that of intestinal-type carcinomas (10.1%, p < 0.0001). Cathepsin D expression of cancer cells was significantly associated with the depth of tumor invasion in both types. The percentage of tumors with high cathepsin D expression in stromal cells was significantly higher in well-differentiated tumors (25.5%) than in moderately differentiated (12.8%) or in poorly differentiated tumors (19.1%). Cathepsin D expression of stromal cells was significantly associated with the depth of tumor invasion in the intestinal type, in contrast to the diffuse type. Highly expressed cathepsin D in cancer cells was associated with a poor prognosis in both types of carcinoma, but in stromal cells highly expressed cathepsin D was associated to a poor prognosis in the intestinal type only. CONCLUSION: These results indicate that cathepsin D expression in cancer cells may play an important role in tumor progression in diffuse-type gastric carcinoma, whereas in the intestinal type of carcinoma, cathepsin D expression in stromal cells may play an important role in tumor progression.