Vascular endothelial growth factor gene polymorphisms associated with prognosis for patients with gastric cancer.

BACKGROUND: The present study analyzed vascular endothelial growth factor (VEGF) gene polymorphisms and their impact on the prognosis for patients with gastric cancer. PATIENTS AND METHODS: Five hundred and three consecutive patients with surgically resected gastric adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tissue and four VEGF (-460T > C, -116G > A, +405G > C, and +936C > T) gene polymorphisms were determined using a polymerase chain reaction-restriction fragment length polymorphism assay. RESULTS: The survival analysis showed no association of three VEGF gene polymorphisms with the prognosis. For the +936C > T polymorphism, the T/T genotype, however, had a worse overall survival (OS) compared with the C/C genotype (P = 0.037). The -460 T/C or C/C genotype was a poor prognostic factor in patients with stage 0 or I gastric cancer (OS: hazard ratio (HR) = 3.96, disease-free survival (DFS): HR = 4.87). In the haplotype analysis, the CACC haplotype was associated with a significantly worse survival when compared with the TGGC haplotype (OS: HR = 1.72, DFS: HR = 1.73). CONCLUSIONS: VEGF gene polymorphisms were found to be an independent prognostic marker for patients with gastric cancer. Consequently, the analysis of VEGF gene polymorphisms can help identify patient subgroups at high risk of a poor disease outcome.     

Vascular Endothelial Growth Factor Expression in Invasive Ductal Carcinoma of Breast

Objective： To detect the expression of VEGF and MVD count in invasive ductal carcinoma of breast to clarify the association of VEGF expression and MVD count with the clinicopathologic features. Methods： The expressions of VEGF, ER, PR, C-erbB-2 and MVD count in 88 cases of invasive ductal carcinoma of breast were examined by immunohistochemistry staining （SP-method）. Results： Sixty-two out of the eighty-eight specimens of breast carcinoma （70.45%） showed positive expression of VEGF. The positive rate of VEGF in cases with lymph node metastasis was higher than that without lymph node metastasis （P〈0.05）. The positive rate of VEGF in stage IIb-Ⅲ was higher than that in stage Ⅰ-Ⅱa （P〈0.05）. The positive rate of VEGF in C-erbB-2 positive group was higher than that in C-erbB-2 negative group （P〈0.05）. Higher expression of VEGF was observed in cases with higher tissue differentiation degree （P〈0.05）. Also, significant higher MVD count was observed in cases with higher tissue differentiation degree （P〈0.01）. The MVD count increased significantly with the increase of the expression of VEGF （P〈0.01）. Conclusion： The result of this study suggested that in invasive ductal carcinoma of breast, angiogenesis and metastasis were mediated mainly by VEGF. The expression of VEGF and MVD might be reference predictors for the biological behavior of breast carcinoma. The antiangiogenic therapy which used VEGF as a target would become a new method to treat patients who were C-erbB-2 positive in the future.     

Contribution of vascular endothelial growth factor to the Nottingham prognostic index in node-negative breast cancer

The prognostic contribution of intratumour VEGF, the most important factor in tumour-induced angiogenesis, to NPI was evaluated by using flexible modelling in a series of 226 N-primary breast cancer patients in which steroid receptors and cell proliferation were also accounted for. VEGF provided an additional prognostic contribution to NPI mainly within ER-poor tumours.     

Vascular endothelial growth factor (VEGF) levels and mutation of the BRCA1 gene in breast cancer patients

The aim of the study was to compare VEGF serum levels in breast cancer patients with and without BRCA1 gene mutation. We enrolled 80 patients, 22 premenopausal and 58 postmenopausal. We found statistically significant lower levels of VEGF in patients with BRCA1 gene mutation as compared with breast cancer patients without this mutation.     

热休克因子(HSF1)在乳腺癌中的表达及与预后的关系

目的：探讨热休克因子（heat shock factor 1，HSF。）在乳腺癌中的表达，及其在乳腺癌预后中所起的作用。方法：采用免疫组织化学方法检测62例手术切除的乳腺癌组织中HSF1的表达，探讨其与临床病理特征的关系及对预后的影响。结果：HSF1在乳腺癌组织中的阳性表达率为29．0％（18／62）。HSF1表达与月经状况存在相关（P=0．004），但与肿瘤大小、淋巴结转移个数以及组织学分级之间均不具相关性。HSF1阴性表达组无病生存期及总生存期均明显优于HSF1阳性表达组（P=0．0057及P=0．0251）。Cox回归单因素分析显示淋巴结转移个数、组织学分级、肿瘤大小、HSF1阳性表达及TNM分期与无病生存期及总生存期均明显相关；Cox回归多因素分析表明腋淋巴结转移个数、组织学分级、肿瘤大小与无病生存期及总生存期明显相关，而HSF1阳性表达及TNM分期最终未进入Cox回归模型。结论：HSF1在乳腺癌中有一定程度的表达，且HSF1表达与乳腺癌患者无病生存期及总生存期的缩短有关，有可能成为判断乳腺癌患者预后的指标。     

Vascular endothelial growth factor acts as an osteolytic factor in breast cancer metastases to bone

Vascular endothelial growth factor (VEGF) is a proangiogenic cytokine that is expressed highly in many solid tumours often correlating with a poor prognosis. In this study, we investigated the expression of VEGF and its receptors in bone metastases from primary human breast tumours and further characterised its effects on osteoclasts in vitro. Breast cancer metastases to bone were immunohistochemically stained for VEGF, its receptors VEGFR1 and 2 (vascular endothelial growth factor receptor 1 and 2), demonstrating that breast cancer metastases express VEGF strongly and that surrounding osteoclasts express both VEGFR1 and VEGFR2. RAW 264.7 cells (mouse monocyte cell line) and human peripheral blood mononuclear cells (PBMCs) were cultured with VEGF, RANKL and M-CSF. VEGF and RANKL together induced differentiation of multinucleated, tartrate-resistant acid phophatase (TRAP)-positive cells in similar numbers to M-CSF and RANKL. The PBMCs were also able to significantly stimulate resorption of mineralised matrix after treatment with M-CSF with RANKL and VEGF with RANKL. We have shown that VEGF in the presence of RANKL supports PBMC differentiation into osteoclast-like cells, able to resorb substrate. Vascular endothelial growth factor may therefore play a role in physiological bone resorption and in pathological situations. Consequently, VEGF signalling may be a therapeutic target for osteoclast inhibition in conditions such as tumour osteolysis.     

Epidermal growth factor receptors and prognosis in primary breast cancer

A retrospective study was performed on 109 human breast tumors stored in liquid nitrogen in order to assess the prognostic value of epidermal growth factor receptor (EGF-R) (median patient follow-up 5 years). A significant inverse relationship was observed between EGF-R and both estrogen (ER) and progesterone receptors (PR). Univariate analysis showed a trend towards a shorter metastasis-free survival both in the overall population and in node-negative patients with EGF-R positive tumors. Multivariate analysis of the overall population showed that lymph-node involvement and PR status were the only significant variables in predicting metastasis-free survival. However, in patients receiving no adjuvant treatment (hormone therapy or chemotherapy), EGF was the only significant variable in the multivariate Cox analysis. No c-erbB-1 amplification was detected in these tumors.     

Vascular endothelial growth factor in node-positive breast cancer patients treated with adjuvant tamoxifen

In 212 postmenopausal women with node-positive oestrogen receptor-positive (ER(LBA)) breast cancer subjected to radical surgery and adjuvant tamoxifen, the risk of 6-year relapse increased with increasing values of intratumoral vascular endothelial growth factor (VEGF) in patients whose tumours had a low/intermediate ER(LBA) content compared to patients with high-ER(LBA) tumours. These findings indicate that tumour progression, activated or sustained by high VEGF levels, may be counteracted in high-ER(LBA) cancers by tamoxifen, which in contrast fails to contrast the metastatic potential in low-ER(LBA) tumours.     

radixin在乳腺癌组织中的表达及其与预后的相关性

目的:观察radixin蛋白表达与乳腺癌临床病理参数的相关性及临床意义。方法:收集散发性乳腺癌标本278例,乳腺纤维腺瘤组织46例,应用SP免疫组化法检测radixin蛋白的表达情况,并分析与乳腺癌患者临床病理参数的相关性。结果:乳腺癌中radixin蛋白表达阳性率为73.7%（205/278）,乳腺纤维腺瘤中radixin蛋白表达阳性率为32.6%（15/46）,与乳腺纤维腺瘤组织比较,radixin蛋白阳性表达率显著高于乳腺纤维腺瘤组织（P＜0.000 1）。在乳腺癌组织中,radixin蛋白表达与患者TNM分期、HER-2表达正相关,在临床分期高、HER-2表达阳性的组织中,radixin蛋白表达阳性率明显增加（P=0.023,P=0.007）。radixin蛋白表达与患者年龄、绝经状态、淋巴结转移、肿瘤大小、p53蛋白表达均未见相关性。生存分析发现,radixin蛋白表达与乳腺癌患者总体生存期无关,radixin阳性表达的乳腺癌患者,RFS时间明显缩短（P＜0.05）。结论:乳腺癌组织中radixin蛋白高表达与患者临床分期、HER-2表达和临床预后相关。     

Prognosis in node-negative breast cancer

In a selected group of 207 breast cancer patients with tumor-free axillary nodes, clinical and pathological features were evaluated as to their relationship to long-term disease-free survival. No clinical feature was found to be prognostically useful. Of pathologic features studied, four appear to have significance. These are (1) the volume of the primary mass, (2) the histologic or nuclear grade, (3) the presence of invasive lobular carcinoma in the primary mass, and possibly (4) the presence of neoplastic cells in intramammary lymphatic vessels. When two or more of these four features are present, prognosis is less favorable than when there is only one, but the influences are not arithmetically additive.     

VEGF和CD44表达与乳腺癌分期的相关性研究

目的：研究血管内皮生长因子（vascular endothelial growth factor,VEGF）和CD44在不同分期乳腺癌中的表达及其相互关系。方法：共收集79例手术标本和12例正常乳腺组织,用免疫组织化学法（S-P法）检测,用免疫组化图象分析系统进行结果处理。结果：乳腺癌中VEGF和CD44的表达水平与正常乳腺组织相比差异具有显著性（P〈0.05）;Ⅰ期与Ⅱ期及Ⅲ期之间相比,VEGF和CD44的表达水平差异同样具有显著性,并且随分期越晚表达越强（P〈0.05）;不同细胞类型之间的差异无显著性（P〉0.05）,而与肿瘤的浸润深度、淋巴结转移、远处器官转移以及肿瘤的TNM分期密切相关（P〈0.05）。结论：VEGF与CD44的表达水平与乳癌分期成正相关,在排除创伤和炎症的前提下,可能提示肿瘤的活跃生长以及潜在转移。     

Vascular endothelial growth factor polymorphisms in gastric cancer development, prognosis, and survival

BACKGROUND: Angiogenesis plays an important role in growth, progression, and metastasis of tumors. Vascular endothelial growth factor (VEGF) overexpression has been associated with advanced stage and poor survival in several cancers. METHODS: The association of functional single nucleotide polymorphisms (SNPs) of VEGF gene with gastric cancer development, prognosis, and survival in a case-control study of 100 gastric cancer Greek patients was evaluated. The genotyping was performed by PCR-RFLP analysis. RESULTS: Our results revealed a marginally significant association of the 634CC genotype (P = 0.042) with increased risk for gastric cancer development. None of the rest of the examined polymorphisms or haplotypes conferred any gastric cancer susceptibility. A strong association between the -2578AA (P = 0.025), -634CC (P = 0.013), +936CT (P = 0.028), +936TT (P = 0.0001) genotypes and a larger tumor size was observed, while the 2578AA and -634CC genotypes were strongly correlated to poor differentiation (P = 0.01) and advanced stage of disease (P = 0.039), respectively. In addition, our results indicated that metastatic disease frequency was more accentuated among the +936TT carriers (P = 0.0035). Interestingly, carrying the -634CC genotype was associated with decreased overall survival rates (46.67%). CONCLUSIONS: The present study suggests that VEGF polymorphisms may contribute to gastric tumor characteristics; these observations, however, requiring further confirmation in a larger multi-ethnic study.     

Positive immunostaining for platelet derived growth factor (PDGF) is an adverse prognostic factor in patients with advanced breast cancer

Previous studies suggest a prognostic role for PDGF in patients with breast cancer, with patients with high plasma PDGF levels or positive response to therapy. We have examined a further 58 patients with advanced breast cancer for the presence of tissue PDGF immunostaining. Patients displaying positive tissue immunostaining for PDGF had a highly significant shorter survival (p = 0.002) than patients with no immunostaining. In addition PDGF positive patients treated with combination chemotherapy had a significantly lower response rate (p = 0.05) than PDGF negative patients. These results confirm our previous findings that PDGF may be an important indicator of shortened survival and treatment failure in patients with advanced breast cancer.     

早期乳腺癌患者术后放化疗后不同基因分型的预后分析

目的:评估早期乳腺癌患者术后不同基因分型放疗后的预后分析。方法:搜集我院2003年-2009年210例早期乳腺癌患者(TNM分期中II期患者,淋巴结转移数目3个以上和/或肿块直径大于5cm),回顾性分析其免疫组化信息及临床病理学资料,210例病人均进行了术后放疗,中位随访59个月(7-132个月),针对不同分型(luminal A、luminal B、HER-2和basal)分析疾病复发(disease recurrences,DR),局部和远处转移以及对侧乳腺癌(contralateral breast cancer,CBC)的发生。所有资料均用SPSS 17.0软件进行分析。结果:中位随访59个月,90%(189/210)病人存活。8年OS和DSS分别为94%(197/210)和96%(201/210)。DR发生率(P=0.004)和CBC发生率(P=0.003)在四种分型中具有统计学意义。HER-2和基底细胞型比luminal A和B型病人更容易复发(P<0.05),而基底细胞型比非基底细胞型更容易发生对侧乳腺癌(P<0.01)。结论:HER-2阳性型和基底细胞型比导管A型和导管B型更容易复发,而基底细胞型乳腺癌更容易发生对侧乳腺癌,基底细胞型预测对侧乳腺癌转移情况具有重要的意义。     

The DNA labelling index: A prognostic factor in node-negative breast cancer

Summary The DNA labelling index (LI), representing the fraction of S-phase cells, was studied in 76 patients operated on for breast cancer from 1975 to 1979. No patient had lymph node involvement following axillary dissection (N–), and no adjuvant medical treatment was given. Patients were classified in one of two groups according to the median LI. Patient distribution by age, tumour size, and receptor status was identical in both groups. A higher frequency of grade 3 tumours was noted in the group with an LI above the median value. The cell proliferation rate was an important discriminative factor for metastatic potential. The probability of survival at 8 years for patients with a high LI was significantly lower than that of patients with low LI (36% versus 100%;p<0.001). Relapse-free survival at 8 years was respectively 56% and 83% (p<0.02). At 2 years, these values were 75% and 100%, indicating the early occurrence of metastases. By contrast, the LI had no prognostic value concerning loco-regional disease recurrence or survival after the appearance of metastasis. No relationship was found in this study between survival and other prognostic factors, namely tumour size, histological grade, or hormone receptor level. The LI currently appears to be the best prognostic factor for N– breast cancer. High risk patients identified by this method could thus be offered adjuvant medical treatment.Presented in part at the 5th Annual Meeting of the European Society for Therapeutic Radiology and Oncology, September 1986, Baden-Baden, FRG     

金属硫蛋白(MT)表达水平与乳腺癌的预后

目的　研究MT在乳腺癌中的表达水平及其与预后的关系。方法　采用免疫组化S -P法 ,检测 91例乳腺癌中MT的表达水平 ,并结合随访资料进行分析。结果　MT主要在细胞核及细胞浆表达 ,癌组织中总阳性率 83 .5 %。MT表达阴性组 3、5年生存率分别为 93 %和 86% ,弱阳性组分别为 88%和 83 % ,阳性组分别为 72 %和 60 % ,强阳性组分别为 62 %和 5 5 % ,差异有显著性 (P <0 .0 5 )。多因素Logistic回归分析提示 ,MT表达具有独立预后价值 ,即表达水平越高 ,预后越差。结论　MT表达水平可作为判断乳腺癌预后的可靠指标。     

腋淋巴结阴性乳腺癌临床病理特征和预后的回顾性分析

目的:分析腋窝淋巴结阴性乳腺癌的临床病理特征及预后的影响因素。方法:收集215例腋窝淋巴结阴性及225例淋巴结阳性乳腺癌患者的临床病理及预后资料,应用χ2检验进行组间比较,以logistic回归进行多因素分析。结果:单因素分析显示,两组间月经状况(P=0.04)、肿瘤大小(P<0.001)、肿瘤分级(P=0.008)、肿瘤位置(P=0.001)差异均有统计学意义。多因素分析显示,肿瘤大小和肿瘤位置是影响淋巴结阴性和阳性乳腺癌患者独立的临床病理因素。两组预后指标分析显示,阴性组有较低的复发率(P<0.001)及远处转移率(P=0.002),有较高的术后生存率(P<0.001)。其中,肿瘤大小(P<0.001)、肿瘤分级(P=0.003)、肿瘤位置(P<0.001)是影响淋巴结阴性乳腺癌患者5年无病生存的因素;肿瘤大小(P=0.012)和肿瘤位置(P<0.001)是影响淋巴结阴性乳腺癌患者5年总生存的因素。结论:淋巴结阴性乳腺癌患者有较好的预后,肿块大小、肿瘤位置是淋巴结阴性乳腺癌患者的独立临床病理因素,也是影响淋巴结阴性乳腺癌患者5年无病生存率及总生存率的预后指标。