VEGF在非小细胞肺癌中表达与血管生成关系及临床意义

目的　采用免疫组化方法观察血管内皮生长因子 (VEGF)及血管内皮细胞膜抗原CD34在非小细胞肺癌(NSCLC)组织、肺炎性假瘤及正常肺组织中的表达状况。方法　用抗VEGF多克隆抗体及CD34单克隆抗体作免疫组化染色 ,免疫标记物阳性细胞和癌组织中微血管密度 (MVD)计数。结果　 81例NSCLC组织上VEGF表达的总阳性率为 72 .84 % ,VEGF在肺癌细胞中主要分布于胞浆、胞膜 ,少量胞外基质也有阳性表达。鳞形细胞癌阳性细胞呈弥散或局灶分布 ,腺癌则呈腺泡状分布。VEGF表达强度同非小细胞肺癌的MVD值紧密相关 ,随VEGF表达强度增高 ,MVD值亦显著增高 (P <0 .0 0 1)。结论VEGF的表达和MVD与NSCLC的发生、发展、转移关系密切 ,可作为NSCLC预后标志     

Cathepsin-D expression in cervical carcinoma and its prognostic significance

An immunohistochemical study was made of cathepsin-D protein expression in each of the three main types of uterine cervical carcinoma (squamous carcinoma, adenosquamous carcinoma and adenocarcinoma) with particular reference to lymph node status and prognosis. Of the 61 cases, 54.1% showed cytoplasmic staining in more than 2.5% of tumour cells counted. Cathepsin-D expression was significantly higher in adenocarcinoma (mean -3.128) than in squamous carcinoma and adenosquamous carcinoma (mean –3.709,P=0.047 using logit transformation). Cathepsin-D had no prognostic value in any of the three tumour types. No relationship was found between cathepsin-D staining and lymph node status and there was no advantage in adding cathepsin-D values to lymph node status. These results suggest that immunostaining for cathepsin-D protein expression is unlikely to be of use as a prognostic marker.     

Prohibitin in squamous cell carcinoma of the lung: its expression and possible clinical significance

rohibitin is localized to mitochondria where it might have a role in the maintenance of mitochondrial function and protection against senescence. In this study, we show that prohibitin is up-regulated in lung squamous cell carcinoma tissues compared with adjacent normal tissues using agarose 2-dimensional differential gel electrophoresis and immunoblotting. Prohibitin expression was further evaluated by immunohistochemistry. We statistically analyzed the association of prohibitin expression with clinicopathologic indicators in 78 patients with lung squamous cell carcinoma. Our data suggested that prohibitin expression was positively correlated with the International Union Against Cancer (UICC) classification of tumor grade (P < .001), pathologic stage (P < .001), tumor size (P = .01), and lymph node metastasis (P = .004). Furthermore, we found that prohibitin expression was an independent prognostic indicator (P = .037) for overall survival of patients with lung squamous cell carcinoma by multivariate analysis using the Cox regression method. These findings may encourage further studies investigating prohibitin function in lung squamous cell carcinoma.     

Small adenocarcinoma of the lung: prognostic significance of central fibrosis chiefly because of its association with angiogenesis and lymphangiogenesis

To clarify the reason why central fibrosis (CF) is an important histological prognostic factor in small adenocarcinoma (SA) of the lung, tumor tissues from 50 patients with SA < or = 2 cm in diameter were investigated using immunohistochemical and in situ hybridization analysis for factors relating to extracellular matrix and vessels. CF was observed in 33/50 cases (66%). In adenocarcinoma areas, positive activity was observed with both primary antibodies and probes for matrix metalloproteinase-2 (MMP-2) in 11/50 patients (22%), membrane-type 1 matrix metalloproteinase (MT1-MMP) in 39/50 patients (78%) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in 49/50 patients (98%). In CF areas, the positive activity of fibroblastic cells was seen for only TIMP-2 in 32/33 patients (97%). In CF areas, both CD34-positive (blood and lymphatic) vessels and D2-40-positive lymphatic vessels were semiquantitatively increased in 16/33 patients (48.5%) by immunohistochemistry. Tumors with increased vessel density were associated with statistically lower disease-free survival curves compared with tumors without increased vessels. Lymphatic vessels in some CF showed intravasation by carcinoma cells. In conclusion, CF could be an important histological prognostic factor in SA chiefly because of its association with angiogenesis and lymphangiogenesis.     

衰变加速因子在非小细胞肺癌中的表达及其临床意义

目的 检测衰变加速因子（decay accelerating factor,DAF,CD55）在非小细胞肺癌（non-small cell lung carcinoma,NSCLC）中的表达,分析其表达与临床分期、化疗用药及预后的关系。方法 免疫组化法检测8例NSCLC癌旁组织和36例NSCLC手术标本中DAF的蛋白表达,分析临床资料。结果 免疫组化结果显示36例NSCLC标本中,共有18例（50．0％）表达DAF,其中18例肺鳞癌中有15例（83．3％）表达,而16例肺腺癌中有3例（18．8％）表达,两者有显著差异（P〈0．05）;不同的病理分期的DAF免疫组化平均积分光密度表达有显著性差异（P〈0．05）;DAF的表达与无病生存期无相关关系（P〉0．05）。结论 NSCLC中有DAF的表达,尤其是肺鳞癌;提示在NSCLC抗体治疗中应同时阻断DAF的免疫抑制效应。     

抗CD34单抗标记血管生成在非小细胞肺癌中的表达及临床意义

目的探讨非小细胞肺癌中 CD34标记的血管生成的表达及临床意义。方法采用免疫组化法检测 81例手术切除的非小细胞肺癌标本中抗内皮细胞表面抗原 CD34单抗标记的血管生成。结果 CD34以其染色的特异性、敏感性及清晰的背景而易于识别。统计学分析显示微血管密度同肺癌临床分期的进展及血行转移密切相关 ,但未发现同淋巴结转移及其它临床病理特征有关。结论肺癌中微血管密度对血行转移的进展有重要作用且同肺癌的发生有关。     

E-cadherin expression in invasive non-lobular carcinoma of the breast and its prognostic significance

BACKGROUND: E-cadherin is a cell adhesion molecule that is expressed in normal breast tissue and is often considered useful as a phenotypic marker in breast cancer diagnosis, with absence of its expression frequently observed in tumours of lobular subtype. However, the clinicopathological and prognostic value of E-cadherin in the more frequent non-lobular types of breast carcinoma is unclear. METHODS AND RESULTS: E-cadherin expression was assessed immunohistochemically in a large and well-characterized series of invasive non-lobular breast carcinoma types (n=1665) with long-term clinical follow-up (median 56 months) using tissue microarray technology, to determine the relationship between its expression and primary tumour characteristics and disease outcome. Only membranous expression of E-cadherin was considered in this study and its expression was categorized as normal (H-score>100) or reduced [absent or below the median (score相似文献   

Histological subtypes of hepatocellular carcinoma: Their clinical and prognostic significance

Assigning a hepatocellular carcinoma (HCC) to an appropriate subtype is important because this guarantees the diagnosis and treatment and allows decisions regarding the prognosis of the patient. HCC subtyping is usually based on the World Health Organization (WHO) classification and the 2019 fifth edition is the latest version. However, the WHO classification system is still in evolution and has limited clinical relevance. We aimed to evaluate the clinical relevance of HCC subtyping and to reappraise some of the major subtypes of HCC. Our archived cases (n = 589) were reclassified according to the 2019 WHO system. The percentage of each subtype was mostly similar to that in the WHO classification. However, on the contrary to the 2019 WHO system, clear cell type HCC was associated with more frequent recurrence or metastasis. Meanwhile, macrotrabecular massive HCC was related to poor prognosis as demonstrated in the 2019 WHO system and should be described in the pathology report. For steatohepatitic HCC, there is a debate on whether it is a true subtype because the steatohepatitis morphology may or may not be present in the background liver. In our study, 44 % of steatohepatitic HCCs (n = 19/43) presented underlying steatohepatitis. Additionally, the background cirrhosis did not influence survival in the HCC patients, although the 2019 WHO system indicates the presence of cirrhosis as a poor prognostic factor. In conclusion, although it is not perfect yet, HCC subtyping based on the 2019 WHO system provides valuable information to manage patients with HCC.     

The prognostic significance of survivin expression in gallbladder carcinoma

Gallbladder cancers (GBC) are characterized by rapid progression, early metastasis, and poor prognosis; the molecular mechanisms of the various signaling pathways involved should be elucidated to develop effective therapies. Survivin, an apoptosis inhibitor protein expressed in the G2/M phase of the cell cycle, plays a role in cell division and affects both cell survival and proliferation. Survivin has been investigated in many types of cancer, and this study aims to examine the relationship of survivin expression in gallbladder cancer patients with clinicopathological features and prognosis. We evaluated demographic characteristics (age, gender), tumor characteristics (histopathological type, differentiation, perineural, and lymphovascular invasion; serosal invasion, surgical margin positivity and lymphocytic response), and Survivin expression immunohistochemically, and we analysed the relationship between these characteristics and prognosis in 47 gallbladder carcinoma cases from 2000 to 2011. Immunohistochemically, while survivin expression was observed in 36 cases, it was absent in 11 cases. Follow‐up data were obtained from 32 patients. Two (8.7%) of 23 cases with a Survivin‐positive tumor were alive at 74th and 35th months, whereas 5 (%55.6) of nine cases with Survivin‐negative tumor were alive at 50th, 89th, 124th, 126th, 131th months. Survivin expression was correlated with short survival (p = 0.043), and the univariate analysis showed that reduced overall survival was associated with age (p = 0.043), male gender (p = 0.038), infiltrative pattern (p = 0.019), lymphovascular invasion (p = 0.004), perineural invasion (p = 0.009), serosal invasion (p = 0.027), ulcer (p = 0.033), and surgical margin positivity (p = 0.022). Despite the low number of patients in our study, the analysis results suggest that survivin positivity might actually be a significant prognostic factor. This finding could be a reference point for targeted treatment studies. However, further studies involving broader series and longer follow‐up are still required for highly lethal gallbladder cancers.     

乳腺癌Akt的表达及其临床意义

目的 本研究试图分析乳腺癌Akt的表达状况,并了解与其它有关生物学标记物的关系,为乳腺癌的治疗探索新的方法提供初步的理论基础.方法 采用免疫组化EnVision两步法检测110例有随访资料的浸润性乳腺癌中pAkt和Akt的表达情况.结果 乳腺癌pAkt和Akt2的阳性定位于肿瘤细胞的胞质或胞核.其pAkt和Akt2的阳性率分别为50%(55/110)和35.5%(39/110).Akt2阳性的患者死亡率高于阴性患者,而pAkt阳性患者的淋巴结转移率及死亡率均高于阴性患者,差异具有统计学显著意义(P<0.01).pAkt和Akt2均与患者的c-erbB-2的阳性表达率呈正相关.但二者与乳腺癌的癌基因p53、凋亡相关基因bcl-2、ER及PR的表达和肿瘤的组织学分级及患者年龄均无相关性.结论 Akt的表达与c-erbB-2的过表达以及与患者较差的预后具有统计学意义的显著关联性,提示Akt的表达情况可能作为评估乳腺癌患者预后的参考指标之一;也表明尤其当患者出现对内分泌治疗抵抗时,摧毁PKB/Akt这一细胞内信号转导途径是否将更有利于乳腺癌的治疗值得进一步的研究.     

CD15 mRNA在原发性肝细胞癌中的表达及其预后意义

目的：研究CD15mRNA表达与原发性肝细胞癌（HCC）侵袭转移和预后关系及与CD44v6和nm23H1的mRNA表达相关性。方法：应用原位杂交和免疫组织化学方法，检测分析HCC组织中CD15mRNA及其蛋白、CD44v6及nm23H的mRNA表达。结果：99例HCC中，CD15mRNA及其 蛋白、CD44和nm23H1的mRNA表达阳性率分别为38．4％、36．7％、41．4％和76．8％。CD15mRNA表达与其 蛋白表达一致，与CD44v6 mRNA表达呈正相关，与nm23H1 mRNA表达呈负相关。CD15mRNA及其蛋白、CD44和nm23H1的mRNA表达均与HCC侵袭转移倾向和患者预后相关。结论：检测CD15表达有可能成为HCC侵袭转移和预后判断的一项新的病理生物学指标。     

Expression of chemokine receptor CXCR7 in colorectal carcinoma and its prognostic significance

Previous studies have shown that chemokine receptor CXCR7 plays critical roles in tumor development. However, the clinicopathological and prognositic significance of CXCR7 in colorectal carcinoma (CRC) has not been fully understood. The aim of our study is to investigate the expression of CXCR7 and its clinical significance in CRC. First, quantitative RT-PCR and Western blot assays were performed to determine the expression of CXCR7 mRNA and protein in 20 paired of CRC tissues and corresponding adjacent non-tumor tissues. Next, immunohistochemistry was performed to detect the expression of CXCR7 protein in another 96 cases of CRC tissues, and analyze its correlation with clinicopathological factors of patients. Finally, the correlation of CXCR7 with 5-year overall survival (OS) and progression free survival (PFS) was statistically analyzed by the Kaplan-Meier method and Cox proportional hazards model. Results showed that the expression levels of CXCR7 mRNA and protein were significantly higher in CRC tissues than in normal tissues. Positive CXCR7 expression was observed to be significantly correlated with lymph nodal metastasis (P < 0.001), distant metastasis (P = 0.017), and advanced TNM stage (P < 0.001). Patients with positive expression of CXCR7 were demonstrated to be associated with worse OS and PFS (P < 0.001, P < 0.001, respectively). Moreover, multivariate survival analysis revealed that CXCR7 expression level might be an independent predictive factor for OS and PFS of CRC patients. Collectively, positive CXCR7 expression in CRC was correlated with tumor development and poor prognosis of patients.     

Expression of protein TARBP1 in human hepatocellular carcinoma and its prognostic significance

Objective: The objective of this study was to analyze the expression of TARBP1 and its clinical significance in hepatocellular carcinoma (HCC). Materials and Methods: 90 patients with primary hepatocellular carcinoma were included in this study. The tumor and paired adjacent non-tumor tissues were collected. TARBP1 expression was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry. Associations of TARBP1 expression with the clinicopathological features were analyzed, and prognosis of HCC patients was evaluated. Results: The result show the expression of TARBP1 mRNA in liver cancer tissues were higher than in the adjacent normal liver tissues in 10 paired samples (P=0.0015). Compared with adjacent normal liver tissues, overexpression of TARBP1 was detected in 61.1% (55/90) HCC patients. TARBP1 expression was associated with the AJCC tumor stage (P=0.004) and clinical stage (P=0.005), and decreased overall survival (P=0.002). In multivariate analysis, TARBP1 expression was an independent prognostic factor for overall survival (Hazard ratio [HR]=2.773, 95% confidence interval [CI] 1.542-4.985; P=0.019). Conclusions: TARBP1 is up-regulated in HCC, and the expression of TARBP1 was associated with the pathological grading and clinical stage. TARBP1 maybe is an independent prognostic marker of HCC patients.     

Wntless在胃腺癌组织中表达及其意义

目的观察Wnt蛋白分泌相关的基因Wntless在胃癌腺癌细胞和癌旁正常黏膜细胞的表达,分析Wntless表达与胃腺癌病理指标之间相关性和临床意义。方法用免疫组化法检测胃腺癌组织和胃癌旁正常黏膜中Wntless的蛋白表达。结果在104例胃癌标本中,Wntless在胃腺癌组织中表达为:7.7%(8/104)例为0或1+、36.5%(38/104)例为2+、55.8%(58/104)例为3+;在癌旁正常黏膜表达为:71.2%(74/104)例为0或1+,19.2%(20/104)例为2+,9.6%(10/104)例为3+。Wntless在胃腺癌组织中的表达显著高于胃癌旁正常黏膜表达(P0.001)。Wntless蛋白表达与肿瘤分化呈正相关(P0.05),与淋巴结转移呈正相关(P0.05)。结论 Wntless蛋白在胃腺癌中高表达,可能对肿瘤发生和进展等发挥了促进作用,并可能为新的靶向治疗提供分子靶标。     

肝细胞性肝癌中MAZ基因的表达及意义

目的探讨MAZ基因在肝细胞性肝癌(hepatocellular carcinoma,HCC)及其癌旁正常组织中的表达,分析其与HCC各临床病理特征及预后的关系。方法采用组织芯片技术和免疫组化法检测75例HCC及其对应癌旁正常组织中MAZ基因的表达,分析其与HCC临床病理特征及与患者预后的关系。结果 MAZ在HCC中的表达(48%,36/75)明显高于其癌旁正常组织(22.67%,17/75),组间比较差异有统计学意义(P0.05)。MAZ表达与HCC患者性别、年龄、病理分级、临床分期、TNM分期、是否合并肝硬化、是否合并乙肝病毒感染、是否有肝癌家族史以及血清AFP、CEA、γ-GT、ALT、AST和ALB水平、是否有淋巴结转移等均无明显相关性,而与肿瘤直径、吸烟与否、饮酒与否显著相关(P0.05)。HCC中MAZ阳性组和阴性组的累计生存率差异有显著性(P0.05),MAZ阳性组患者的术后无瘤生存时间明显低于阴性组,提示MAZ表达上调可能导致患者的预后更差。结论 MAZ基因表达上调可能与HCC的发生、发展密切相关。     

Lack of prognostic significance of angiogenesis in canine melanocytic tumours

The prognostic significance of angiogenesis in some canine tumours has been investigated, but little is known about its relevance in canine melanocytic tumours (MTs). The aim of this study was to evaluate the prognostic significance of angiogenesis in canine MTs. A total of 36 cutaneous melanocytomas (benign MTs), 40 cutaneous melanomas (malignant MTs) and 43 oral melanomas were studied. Survival data were available for a subset of 59 cases. Microvessel density (MVD) and endothelial area (EA) were determined by immunolabelling using an antibody specific for von Willebrand factor (vWF). Mean MVD (expressed as the number of microvessels per mm(2)) was 129 ± 14 in melanocytomas, 191 ± 16 in cutaneous melanomas and 208 ± 16 in oral melanomas. Mean EA (expressed as the percentage of the total area) was 1.5 ± 0.14 in melanocytomas, 2.6 ± 0.2 in cutaneous melanomas and 2.4 ± 0.3 in oral melanomas. The differences in MVD and EA between melanocytomas and melanomas were significant (P = 0.001 and P = 0.003, respectively). MVD and EA were significantly correlated between cutaneous and oral MTs (r = 0.54; P <0.001 and r = 0.63; P <0.001, respectively). MVD and EA were not related to survival in cutaneous and oral MTs. In conclusion, tumour vascularization was higher in melanomas than in melanocytomas, but it seemed to have no prognostic significance in these tumours.     

The prognostic relevance of angiogenesis and mast cells in squamous cell carcinoma of the oesophagus

AIMS: Angiogenesis, an important prognostic factor in several tumours, is a complex event mediated by angiogenic factors released from cancer cells and host immune cells. Among the host immune cells, a role has been implicated for mast cells in tumour progression via promoting angiogenesis. Data have been recorded that indicate a correlation between intratumoral neovascularisation, as assessed by microvessel density (MVD), and prognosis in squamous cell carcinoma (SCC) of the oesophagus. However, a correlation between mast cell density (MCD) and either prognosis or angiogenesis has not been delineated yet in this disease. The aim of this study was to investigate the prognostic value of MVD and MCD in SCC of the oesophagus. The correlation between MVD and MCD was also evaluated. METHODS: MVD and MCD were investigated in tumour specimens from 53 patients diagnosed with SCC of the oesophagus. Intratumoral microvessels were stained with anti-CD34 antibody and mast cells with toluidine blue before being measured by light microscopy. RESULTS: Both MVD and MCD were associated with the depth of wall invasion, lymph node metastasis, and tumour progression (stage). A significant correlation was noted between MVD and MCD values (r = 0.72). The prognosis was significantly worse in patients with high MVD (> or = 92) and high MCD (> or = 18) values. Multivariate analysis indicated that MVD and stage were independent predictors of survival. CONCLUSIONS: These findings support the suggestion that MVD is a reliable prognostic marker in SCC of the oesophagus. Moreover, MCD may have a role in the angiogenesis of these tumours and might be responsible for their aggressive behaviour.