CD3-zetachain expression of intratumoral lymphocytes is closely related to survival in gastric carcinoma patients

BACKGROUND: Impaired or reduced CD3 zeta chain (CD3-zeta) expression in T cells has been identified in various cancers and may be associated with an ineffective immune response. The clinical significance of CD3-zeta chain expression in tumor-infiltrating lymphocytes (TILs) in gastric carcinoma remains unclear. METHODS: The authors immunohistochemically investigated CD3-zeta expression in TILs in 185 patients who had undergone curative gastrectomy. CD3-zeta/CD3 epsilon (CD3-epsilon) ratios were calculated. Patients were divided into two groups: a normal CD3-zeta group (n = 121) and a reduced CD3-zeta group (n = 64). Patients with a zeta per epsilon ratio of greater than 66% were placed in the normal CD3-zeta group. RESULTS: Patients in the normal CD3-zeta group had fewer lymph node metastasis (P < 0.01) and a shallower depth of invasion (P < 0.05) than those in the reduced CD3-zeta group. The 5-year survival rate was 72% in the normal CD3-zeta group, which was significantly better than that in the reduced CD3-zeta group (55%; P < 0.01). When stratified according to clinical stage, the prognostic value was significantly different only in Stage IV patients. Multivariate analysis showed that CD3-zeta expression was an independent prognostic factor (P = 0.03) next to depth of invasion and lymph node involvement. CONCLUSIONS: Reduced CD3-zeta expression in TILs was strongly correlated with progressive disease in gastric carcinomas. CD3-zeta expression in TILs is considered an immunologic, independent prognostic marker in gastric carcinoma patients. CD3-zeta normalization with cytokine treatment may lead to prolonged survival in advanced gastric carcinoma patients.     

Differences in the recognition of tumor-specific CD8+ T cells derived from solid tumor,metastatic lymph nodes and ascites in patients with gastric cancer

We established gastric cancer-specific CD8⁺ T-cell (T_CD8⁺) lines derived from different lymphocyte sources in the same patients by repeated stimulation with mitomycin-C-treated autologous tumor cells with low-dose interleukin-2, and we compared recognition patterns among the T_CD8⁺ derived from solid tumor, lymph node metastasis and ascites in the same patient (n = 3) to determine their similarities and differences for therapeutic purposes. We confirmed that gastric cancer-specific T_CD8⁺ lines can be isolated, in a MHC class I-restricted manner, from solid tumors, metastatic lymph nodes and malignant ascites. T_CD8⁺ lines derived from tumor-infiltrating lymphocytes (TIL) in solid tumor recognized autologous tumor cells derived from solid tumor, but not autologous tumor cells derived from ascites or metastatic lymph node, while T_CD8⁺ lines derived from tumor-associated lymphocytes (TAL) in malignant ascites recognized autologous tumor cells derived from ascites, but not tumor cells from solid tumor or metastatic lymph node. Furthermore, T_CD8⁺ lines derived from regional lymph node lymphocytes (RLNL) recognized autologous tumor cells derived from metastatic lymph nodes, but not tumor cells derived from ascites. No significant differences were seen in MHC class I expression among the tumors derived from solid tumor, lymph node metastasis or ascites in the same patient. This suggests that there are differences of recognition patterns among the TILs, TALs and RLNLs in the same patient and that it is important to consider the source of lymphocytes, e.g., a combination of TILs, TALs and RLNLs, for adoptive immunotherapy in gastric cancer patients. Int. J. Cancer 71: 978-981, 1997. © 1997 Wiley-Liss Inc.     

Relationship between the expressions of PD-L1 and tumor-infiltrating lymphocytes in oral squamous cell carcinoma

Tumor-infiltrating lymphocytes (TILs) are considered to represent immune reactions of the host to a malignant tumor. Programmed death receptor ligand-1 (PD-L1) is a surface protein that blocks the function of T lymphocytes and is expressed on cancer cells. Tumor-associated fibroblasts (TAFs), which influence tumor growth have also been reported to express PD-L1 and thus inhibit TILs. In the present study, we investigated the densities of CD4⁺/CD8⁺ TILs, PD-L1 expression of tumor cells and TAFs in oral squamous cell carcinoma (OSCC). Forty-five cases of OSCC were selected. We evaluated PD-L1 expression and the infiltration degree of each lymphocyte by immunohistochemical examination. These data were analyzed in connection with clinicopathological factors. Peritumoral CD8⁺ TILs were observed in every patient with OSCC, and their densities were correlated with lymph node metastasis (P < 0.001), tumor size (P = 0.003), and clinical stage (P < 0.001). PD-L1 expression on OSCC cells was observed in 39 cases and was associated with the lower density of intratumoral CD8⁺ TILs (P = 0.047). PD-L1 expression of tumors <4 cm in size was correlated with the histological grade of the tumor (P = 0.022). TAFs were positive for PD-L1 in 18 cases. Peritumoral TILs were significantly associated with tumor size, lymph node metastasis and clinical stage. Though PD-L1 expressed by OSCC cells did not affect patients’ survival, its correlation with decreased number of intratumoral TILs suggests that the development of a strategy to block the interactions of PD-L1 with TIL would be a useful tool for inhibiting tumor growth.     

CD168在胃癌组织中的表达及预后意义

目的 探讨胃癌组织中透明质酸介导的细胞游走受体(CD168)的表达情况与各临床病理因素及其预后的关系,评估其在胃癌侵袭转移过程中的作用及预测胃癌患者预后的价值.方法 采用免疫组织化学法检测72例胃癌组织和26例正常胃黏膜组织中CD168的表达情况.同时评估CD168的表达与临床病理因素(年龄、性别、组织学、肿瘤浸润深度、淋巴结转移和临床分期)之间的关系.用Kaplan-Meier法评估胃癌患者术后5年生存率.结果 胃癌组织中CD168阳性表达率为58.3％,与正常胃黏膜中的阳性表达率(19.2％)比较,差异有统计学意义(P=0.001);CD168阳性表达率与肿瘤分化程度(P=0.001)、淋巴结转移(P=0.003)、临床分期等(P=0.020)有显著相关性.CD168阳性表达率与年龄、性别、肿瘤大小和肿瘤浸润深度无显著相关性.胃癌患者的生存期分析显示,CD168阴性组5年生存率(67.2％)显著高于CD168阳性组5年生存率(29.8％),两组间差异有统计学意义(P=0.01).结论 CD168高表达与胃癌的浸润和转移密切相关,可以作为预测胃癌预后的一个生物学指标.     

Expression of Fas antigen (CD95) in peripheral blood lymphocytes and in liver-infiltrating, cytotoxic lymphocytes in patients with hepatocellular carcinoma

BACKGROUND: Fas-expressing cytotoxic T lymphocytes (CTLs) are important antitumor immune effector cells in patients with hepatocellular carcinoma (HCC). The role of transforming growth factor beta 1 (TGF-beta1) in modulating the expression of Fas by CTLs is not known in HCC. The objectives of this study were to characterize the expression of Fas by CTLs and natural killer (NK) cells among peripheral blood lymphocytes (PBLs) and tumor-infiltrating lymphocytes (TILs) in patients with HCC and to correlate the association, if any, with serum TGF-beta1 levels. METHODS: PBLs from 18 patients with HCC and TILs from 5 HCC liver specimens were isolated, and Fas expression was analyzed by three-color flow cytometry. The results were compared with results from normal control volunteers (n = 19 individuals). Serum TGF-beta1 levels in patients with HCC were measured by enzyme-linked immunosorbent assay. RESULTS: The median percentage of Fas expression by CD3 positive T cells was significantly higher in patients with HCC compared with normal controls (54.37% vs. 32.03%, respectively; P = 0.0036), and this was attributable solely to Fas expression by CD4 positive PBLs (54.46% vs. 34.90%, respectively; P = 0.0234). In contrast, Fas expression was significantly higher in all the subtypes of TILs (CD3 positive, CD4 positive, CD8 positive, NK cells, and natural T cells) compared with controls (all P values were < 0.001). Tumor size was inversely proportional to the TGF-beta1 levels (correlation coefficient [r] = -0.725; P < 0.0001), which were correlated inversely with Fas expression by CD4 positive PBLs (r = -0.516; P = 0.01). CONCLUSIONS: In patients with HCC, TILs exhibit significantly increased expression of Fas compared with PBLs that may enhance their susceptibility to apoptotic mechanisms. Larger tumors were associated with lower serum TGFbeta1 levels, and this was correlated with greater Fas expression by CD4 positive PBLs.     

乳腺癌患者淋巴结CD4＋CD25＋T细胞和相关细胞因子的检测及相关性分析

目的探讨CD4＋CD25＋T细胞在乳腺癌发生、发展中的作用。方法将取自35例乳腺癌患者的105个肿大淋巴结,制备成单细胞悬液,应用流式细胞仪检测CD4＋CD25＋T细胞比例及CD4＋CD25-、CD8＋T细胞、NK细胞的相对水平。采用定量RT-PCR法,检测IL-2、IL-10、TGF-β1和IFN-γ的细胞因子水平。结果乳腺癌患者淋巴结中的CD4＋CD25＋T细胞水平（在CD4＋T细胞中的百分含量）与淋巴结转移相关,转移淋巴结中其水平明显高于未转移淋巴结。乳腺癌患者淋巴结中CD4＋CD25＋T细胞与CD4＋CD25-、CD8＋T细胞和NK细胞的水平呈负相关关系。乳腺癌患者淋巴结中CD4＋CD25＋T细胞水平与TGF-β1呈正相关,与IL-2、IL-10、IFN-γ无相关性。乳腺癌患者淋巴结中TGF-β1、IL-10、IFN-γ水平与淋巴结转移相关,转移淋巴结中TGF-β1、IL-10含量高而IFN-γ含量较低。IL-2与淋巴结转移无相关性。结论乳腺癌患者转移淋巴结中的CD4＋CD25＋T细胞水平高于未转移淋巴结。     

肿瘤浸润性T淋巴细胞ζ链异常表达在舌癌预后中的价值

[目的]探讨肿瘤浸润性T淋巴细胞CD3-ζ链异常表达在舌癌预后预测中的价值。[方法]利用免疫组化法检测115例舌癌CD3-ζ链的异常表达,分析方法是寿命表法、Kaplan—Meier法和Speannan相关检验。[结果]CD3-ζ链异常表达（CD3-ζ减少）者占42．61％（49／115）。CD3-ζ链正常表达组患者的3、5年累积生存率分别为84．69％、82．60％,异常表达组为69．23％、66．67％（P=0．0362）,单因素分析提示CD3-ζ链异常表达影响患者预后。CD3-ζ链异常表达与颈淋巴结病理阳性组患者的3、5年累积生存率最低（30．00％、30．00％）,其次分别是CD3-ζ链正常表达与颈淋巴结病理阳性组（66．67％、66．67％）,CD3-ζ链异常表达与颈淋巴结病理阴性组（79.32％、76．14％）患者,而CD3-ζ链正常表达与颈淋巴结病理阴性组患者的3、5年累积生存率最高（87．51％、85．01％）（P=0．0000）。[结论]肿瘤浸润性T淋巴细胞CD3-ζ链异常表达在舌癌预后评价中的有一定价值,结合颈淋巴结病理状态能更加准确地预测患者预后。     

High number of intraepithelial CD8+ tumor-infiltrating lymphocytes is associated with the absence of lymph node metastases in patients with large early-stage cervical cancer

In a prospective study, we have examined the tumor-specific immune response in a group of 59 patients with human papillomavirus (HPV) 16-positive (HPV16(+))-induced or HPV18(+)-induced cervical cancer. Local antitumor immunity was analyzed by the enumeration of tumor-infiltrating dendritic cells and CD4+, CD8+, and regulatory T cells as well as by calculation of the ratio of CD8+/CD4+ T cells and CD8+/regulatory T cells. Systemic tumor-specific immunity was assessed by determination of the HPV E6- and/or E7-specific T-cell response in the blood of these patients. Finally, these variables were evaluated with respect to known histopathologic prognostic variables, including the absence (LN-) or presence (LN+) of lymph node metastases. Stratification according to the lymph node status of patients revealed a significantly stronger CD8+ T-cell tumor infiltration, a higher CD8+/CD4+ T-cell ratio, and higher CD8+/regulatory T-cell ratio in the group of patients in which the tumor failed to metastasize to the tumor-draining lymph node. Subdivision according to the presence (IR+) or absence (IR-) of circulating HPV-specific T cells disclosed that the highest number of tumor-infiltrating CD8+ T cells was found in the group of LN- patients displaying a concomitant systemic tumor-specific immune response (LN-IR+). CD8+ T-cell infiltration in LN-IR- patients was comparable with that of LN+ patients. In cervical cancer, the absence of lymph node metastases is strongly associated with a better prognosis. Our data indicate that, especially in a subgroup of LN- patients, a strong and effective interaction between immune system and tumor exists. This subgroup of cervical cancer patients may have the best prognosis.     

内皮素-1和C D43在宫颈鳞状细胞癌组织中的表达及临床意义

目的:探讨内皮素-1(ET-1)和CD34在侵袭性宫颈鳞状细胞癌中的表达及临床意义.方法:研究对象为54例宫颈鳞状细胞癌患者.收集所有宫颈癌患者癌组织.应用免疫组织化学方法检测癌组织中ET-1和CD34蛋白表达水平.分析ET-1和CD34表达与宫颈癌临床病理参数相关性.结果:63％患者癌组织中ET-1高表达,而且与肿瘤...     

肿瘤相关CD66b阳性中性粒细胞对预测宫颈癌Ⅰb至Ⅱa期复发的价值

  目的  :探讨宫颈癌组织中的多形核嗜中性粒细胞（polymorphnuclear neutrophil,PMN）数量在预测宫颈癌复发中的作用。  方法  回顾性分析1999年2月至2006年12月湖北省妇幼保健院及武汉大学中南医院92例初治宫颈癌Ⅰb~Ⅱa期患者的临床病理资料。采用免疫组织化学法检测宫颈癌组织中阳性CD66b的PMN数量,计算PMN数量平均值。将患者按宫颈癌组织中PMN浸润数量分组,数量 > PMN平均值为A组,数量≤PMN平均值为B组。以无复发生存（recurrence free survival,RFS）为结点,采用Kaplan-Meier法进行单因素分析,采用Cox风险回归模型进行多因素分析。  结果  A组的RFS期明显短于B组（P=0.001）。单因素及Cox风险回归模型多因素分析结果显示,腺癌（HR为3.020,95%CI为1.340~6.805,P=0.008）、淋巴结转移（HR为2.450,95%CI为1.065~5.637,P=0.035）、PMN浸润数量增加（HR为2.866,95%CI为1.274~46.447,P=0.011）为宫颈癌患者RFS的独立危险因素。  结论  宫颈癌组织中PMN数量的增加与宫颈癌患者RFS期缩短相关,是宫颈癌患者预后不良的一个潜在预测指标。      

The prognostic value of primary tumor size in papillary and follicular thyroid carcinoma

BACKGROUND: A delay in the diagnosis of differentiated thyroid carcinoma often leads to larger tumors, higher prevalence rates of distant metastasis, and earlier cause-specific deaths. Threshold tumor diameters for extrathyroidal growth, lymph node spread, and distant metastasis in papillary (PTC) and follicular thyroid carcinoma (FTC) remain to be defined. METHODS: A comparative correlation of primary tumor size and extrathyroidal growth, lymph node spread, and distant metastasis was performed for 500 institutional patients who received surgery for PTC or FTC. RESULTS: There were 366 patients with PTC (73.2%) and 134 patients with FTC (26.8%). Multifocality (23.5% vs. 9.0%; P < 0.001) and lymph node metastasis (40.2% vs. 19.4%; P < 0.001) were more common in the patients with PTC than in those with FTC. Patients with FTC were older at first diagnosis (51.6 vs. 47.0 years; P = 0.01) compared with the patients with PTC. The FTC tumors were almost twice as large (39.9 vs. 20.6 mm; P < 0.001), and patients had a higher prevalence of distant metastasis (17.9% vs. 6.3%; P < 0.001). When primary tumor diameter was accounted for, cumulative risks of extrathyroidal growth and lymph node metastasis were higher in patients with PTC than in patients with FTC (P < 0.001; log-rank test). In striking contrast, the cumulative risk of distant metastasis was the same for PTC and FTC tumors of equal size (P = 0.89; log-rank test) and increased once the primary tumor size was > 20 mm. Pulmonary metastasis was an earlier event than bone metastasis. CONCLUSIONS: The data suggested that earlier intervention is warranted to keep suspicious thyroid nodules from growing > 20 mm (or greater than T1) and spreading to distant organs.     

CD8+tumor‐infiltrating lymphocytes at primary sites as a possible prognostic factor of cutaneous angiosarcoma

Tumor‐infiltrating lymphocytes (TILs) have been reported as a prognostic factor in various cancers and are a promising target for immunotherapy. To investigate whether TILs have any impact on the prognosis of angiosarcoma patients, 55 non‐treated patients (40 patients at stage 1 with cutaneous localized tumors, 4 patients at stage 2 with lymph node metastases and 11 patients at stage 3 with distant metastases) with angiosarcoma were evaluated retrospectively by immunohistochemistry stained CD4, CD8, FOXP3 and Ki67. The Kaplan–Meier method was used to estimate overall survival with patients at stage 1. Survival differences were analyzed by the log‐rank test. Patients with higher numbers of CD8⁺ TILs in their primary tumors survived significantly longer compared with patients with lower values. Moreover, the number of CD8 in TILs was positively correlated with a distant metastasis‐free period. The total number of primary TILs (CD4 plus CD8) and CD8⁺ primary TILs of stage 3 patients with distant metastases was positively correlated with their overall survival. To evaluate whether CD8⁺ effector T cells are activated or differentiated, flow cytometric analysis of peripheral blood mononuclear cells (PBMC) was performed. The percentages of CD8⁺ T cells producing IFN‐γ in PBMC were significantly higher in patients with angiosarcoma (n = 10) compared not only with that of healthy controls (n = 20) but also patients with advanced melanoma (n = 11). These results suggest that anti‐tumor immunity is clinically relevant in angiosarcoma.     

甲状腺乳头状癌合并桥本甲状腺炎的颈淋巴结转移特点及相关因素分析

目的:探讨甲状腺乳头状癌(papillary thyroid carcinoma,PTC)合并桥本甲状腺炎(Hashimoto,s thyroiditis,HT)患者颈淋巴结转移的临床特点及其相关因素,为颈淋巴结清扫术的选择提供临床依据.方法:对2006年1月-2011年12月在本科接受外科手术的205例PTC合并HT患者颈淋巴结转移的临床特点及相关影响因素进行回顾性分析.这些患者均接受了颈淋巴结清扫术.结果:PTC合并HT患者的颈淋巴结转移率为52.7％ (108/205),颈淋巴结转移遵循以中央区为第1站的规律,中央区淋巴结转移率(50.2％,103/205)高于侧颈区淋巴结转移率(15.1％,31/205) (P=0.000).性别(r=0.009,P=0.904)、术前血清促甲状腺激素水平(r=-0.050,P=0.536)和原发肿瘤病灶数(r=0.119,P＝0.096)均与淋巴结转移无明显相关性;年龄(r=-0.140,P=0.043)、原发肿瘤大小(r=0.185,P=0.010)和肿瘤外侵(r=-0.340,P=0.010)均与淋巴结转移相关.结论:鉴于PTC合并HT患者颈中央区淋巴结转移率较高,应常规行中央区淋巴结清扫术;侧颈区淋巴结由于转移假阳性率较高,因此在考虑行淋巴结清扫时应持谨慎态度.对于青少年或年龄≥45岁、原发肿瘤较大以及肿瘤外侵的患者,可酌情考虑Ⅰ期行侧颈区淋巴结清扫术.     

333例声门型喉癌颈淋巴结转移与预后的关系

背景与目的:声门型喉癌颈淋巴结转移率不高,颈部处理尚无统一认识.本研究探讨声门型喉癌颈淋巴结转移的预后及其影响因素.方法:收集1992年1月1日至2000年12月31日中山大学肿瘤防治中心收治的333例声门型喉癌患者的临床资料,对颈淋巴结转移情况、预后及颈部处理进行回顾性分析.结果:全组患者总的颈淋巴结转移率9.61%(32/333),隐性淋巴结转移率6.23%(20/321).绝大多数转移淋巴结位于同侧Ⅱ、Ⅲ、Ⅳ区(28/32).病理分化级别与总的淋巴结转移率(P=0.092)及隐性淋巴结转移率(P=0.067)无明显相关性.总的淋巴结转移率(P=0.002)及隐性淋巴结转移率(P=0.015)随T分期升高而增高.cN0患者颈选择性放疗对隐性淋巴结转移率的影响无显著性(P=0.363).初治cN 组(3、5年生存率分别为56.25%、46;67%)预后差于初治cN0组(3、5年生存率分别为88.70%、85.37%)(P＜0.001);初治cN0组中出现隐性淋巴结转移的预后(3、5年生存率分别为68.18%、63.31%)差于未出现隐性淋巴结转移(3、5年生存率分别为89.00%、85.55%):初治cN 组有淋巴结转移的预后(3、5年生存率分别为41.67%、16.67%)差于初治cNO组中出现隐性淋巴结转移组(3、5年生存率分别为68.18%、63.31%)(P=0.004).结论:声门型喉癌绝大多数转移淋巴结位于同侧Ⅱ、Ⅲ、Ⅳ区,最多位于同侧Ⅱ区;声门型喉癌颈淋巴结转移影响预后.     

乳腺癌微环境中T细胞与临床病理因素的相关性

目的:探讨乳腺癌中间质肿瘤浸润淋巴细胞（TILs）包括CD8+TILs、CD4+TILs、三维淋巴结构（TLS）与临床病理因素和分子亚型的相关性。方法:收集我院2015年至2017年乳腺癌标本200例,经常规石蜡包埋制片,判读HE染色切片间质TLS个数,采用免疫组织化学SP法检测200例病例中CD8+TILs和CD4+TILs浸润密度。结果:乳腺癌间质CD8+TILs、CD4+TILs、TLS与SBR分级、病理TNM分期、Ki67、p53呈正相关;CD8+TILs和CD4+TILs与淋巴结转移呈正相关;与患者年龄呈负相关（均P＜0.05）。CD8+TILs和CD4+TILs呈正相关（P＜0.05）。TLS以CD4+TILs为主,分别与CD8+TILs和CD4+TILs呈正相关（均P＜0.05）。在乳腺癌不同分子亚型中CD8+TILs、CD4+TILs和TLS存在显著差异。结论:乳腺癌中浸润的CD8+TILs、CD4+TILs、TLS反映局部肿瘤微环境的免疫状态,三者密切相关。乳腺癌组织中增多的CD4+TILs诱导CD8+TILs产生CD8+Treg细胞参与乳腺癌的免疫抑制,导致乳腺癌局部免疫功能下降,促进乳腺癌进展及转移。结合乳腺癌分子亚型和局部免疫状态的分析将更有利于预测乳腺癌进展的生物学潜能和对分子靶向性疗效和预后的评估。     

Local recurrence in mismatch repair-proficient colon cancer predicted by an infiltrative tumor border and lack of CD8+ tumor-infiltrating lymphocytes

PURPOSE: The identification of colon cancer patients at high risk of local recurrence is necessary to improve the selection of patients for more tailored treatment protocols. The aim of this study was to develop a predictive model of local recurrence by assessing the independent predictive effect of 7 clinicopathologic features, 24 protein markers of tumor progression, and their multifeature combinations in mismatch repair-proficient colon cancers. EXPERIMENTAL DESIGN: Immunohistochemistry for 24 protein markers was done on 269 patients with complete clinicopathologic data. After univariate and multivariable analyses, independent predictors of local recurrence were identified and their multifeature combinations were analyzed. Kaplan-Meier and Cox proportional hazards regression were done for survival analysis. RESULTS: Local recurrence was observed in 119 patients (55.8%). Independent predictors of tumor recurrence were lymph node involvement (P = 0.006), absence of CD8+ tumor-infiltrating lymphocytes (TIL; P < 0.001), and infiltrative tumor margin (P < 0.001). This independent effect persisted after adjusting for adjuvant therapy. Risk of recurrence was 0.75 and the 5-year survival rate was 8.8% in patients with these three adverse features. Node-negative patients with an infiltrative tumor margin and absence of CD8+ TILs were identified as high risk with a probability of 0.55 for recurrence and a 60% 5-year survival rate. The remaining node-negative cases fared significantly better with risks ranging from 8% to 26% and 5-year survival rates reaching 97.6%. CONCLUSIONS: An infiltrative tumor margin and absence of CD8+ TILs are highly predictive of local recurrence in node-negative mismatch repair-proficient colon cancer and may help to identify high-risk patients who may benefit from adjuvant chemotherapy.     

中晚期喉癌患者颈部淋巴结转移状况及相关影响因素分析

目的：探讨中晚期喉癌患者颈部淋巴结转移情况及相关影响因素。方法回顾性分析68例中晚期喉癌患者颈部淋巴结转移与肿瘤原发部位、T分期、N分期、病理分级、临床分期、淋巴结受累侧数的关系,应用Logistic回归分析喉癌淋巴结转移相关因素和喉癌患者死亡的危险因素。结果68例患者中有16例发生淋巴结转移,转移率为23．53％。 Logistic回归分析的因素包括年龄、性别、病变部位、病理分级、T分期、N分期、临床分期、淋巴结受累侧数,结果显示,病理分级（P＝0．001）、T分期（P＝0．021）、临床分期（P＝0．007）是喉癌淋巴结转移的相关因素。淋巴结转移（P＝0．001）与T分期（P＝0．003）是喉癌患者死亡的危险因素,而N分期和病理分级对于喉癌患者死亡的影响差异无统计学意义。结论中晚期喉癌患者颈部淋巴结转移情况与病理分级、T分期、临床分期有关,喉癌患者的死亡因素与淋巴结转移和T分期相关。     

Vascularity index as a novel parameter for the in vivo assessment of angiogenesis in patients with cervical carcinoma

BACKGROUND: The importance of angiogenesis now is well recognized. Conventionally, tumor angiogenesis is assessed by determination of microvessel density (MVD) in the surgical specimen. This study examines tumor angiogenesis using power Doppler ultrasound and a quantitative image processing system. The authors hope to develop an in vivo and noninvasive method for quantitating tumor angiogenesis. METHODS: Thirty-five patients with FIGO Stage IB-IIA cervical carcinoma exhibiting visible cervical tumors by transvaginal ultrasound were included in this study. All patients underwent radical abdominal hysterectomy and pelvic lymph node dissection. Transvaginal power Doppler ultrasound was performed before surgery to search for blood flow signals from the tumor. The intratumoral vascularity index (VI) and resistance index (RI) were calculated. The VI was defined as the number of colored pixels divided by the number of total pixels in the defined tumor section. Maximal VI and minimal RI of a certain tumor were used for analysis. Clinical and pathologic data also were recorded. The MVD of the excised tumor was assessed immunohistochemically using a monoclonal antibody against CD34. RESULTS: Significantly higher VI values were noted in Stage II tumors compared with Stage 1 tumors (19.01+/-10.90% vs. 9.09+/-6.59%; P = 0.008), tumors invad-ing+/-50% of the cervical stroma compared with tumors invading < 50% of the cervical stroma (13.20+/-8.20% vs. 5.72+/-5.00%; P = 0.003), tumors with lymphovascular emboli compared with tumors without lymphovascular emboli (17.28+/-8.26% vs. 6.98 +/- 5.09%; P = 0.001), and tumors with pelvic lymph node metastases compared with tumors without pelvic lymph node metastases (26.16+/-7.88% vs. 8.00+/-4.95%; P = 0.021). None of the variables mentioned earlier showed a significant difference in terms of the RI values. No correlation was noted between intratumoral RI and VI in respective tumors (P = 0.53). Analysis of VI revealed linear regression with regard to tumor size (P < 0.001, correlation coefficient [r] = 0.586) and depth of stromal invasion (P = 0.002, r = 0.497). In addition, the MVD exhibited a linear relation with VI (P = 0.006, r = 0.454), tumor size (P = 0.005, r = 0.465), and depth of stromal invasion (P = 0.009, r = 0.436) using simple regression analysis. No correlation could be found between MVD and RI. CONCLUSIONS: In cervical carcinoma, intratumoral VI assessment by power Doppler ultrasound and quantitative image processing system showed better correlation with tumor stage, tumor size, and pathologic findings including depth of stromal invasion, lymphovascular emboli, and pelvic lymph node metastases than intratumoral RI. The in vivo indicator of angiogenic activity (VI) is well correlated with the conventional indicator of tumor angiogenic activity (MVD). Thus, VI could be a useful parameter for the in vivo assessment of global tumor angiogenesis.     

SPARC在Ⅱ期舌体鳞癌组织中的表达及意义

背景与目的：已经发现富含半胱氨酸的酸性分泌蛋白（secreted protein acidic and rich in cysteine,SPARC）在多种恶性肿瘤中有不同程度的表达。并且与肿瘤生物学行为、预后相关。本研究通过检测SPARC在临床Ⅱ期舌体鳞癌的表达,分析其表达强度与舌癌预后的关系。方法：收集55例中山大学肿瘤防治中心头颈外科1999年1月至2003年12月临床Ⅱ期（T2NOM0）舌体鳞癌术后标本．25例舌炎症旁组织作对照,免疫组化定性检测SPARC的表达。分析其表达强度与舌癌患者生存、复发、隐匿性淋巴结转移的关系。结果：55例舌癌术后标本中SPARC阳性率为49．1％,25例对照舌上皮组织不表达（P〈0．001）：SPARC阳性患者的5年累积生存率为30．0％,SPARC阴性患者5年累积生存率为85．3％,统计学分析差异有统计学意义（P=0．005）;SPARC在隐匿性淋巴结转移阳性与阴性患者表达率分别为86．7％及35．0％,差异有统计学意义（P=0．001）。SPARC在复发与否患者表达率分别100％及31．7％,差异有统计学意义（P〈0．001）。SPARC的表达与隐匿性淋巴结转移、复发呈正相关,相关系数依次为0．460（P〈0．001）、0．595（P〈0．001）。结论：SPARC在临床Ⅱ期舌体鳞癌中表达高于正常舌上皮组织,其表达与生存率、隐匿性淋巴结转移、复发呈正相关。